John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


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Memorial Day Closure

Friday, May 24, 2019, 3:36 PM ET

Akina, Inc. will be closed May 27, 2019 for Memorial Day. Orders placed at that time will be processed the following day.

PLA-PEG-Maleimide from PolySciTech used in development of long-lasting vaccines against infections

Tuesday, May 14, 2019, 2:08 PM ET

The human immune system can be visualized as an angry guard dog on a long chain. The dog has enough power and bite to destroy just about anything within its area but, in order to be effective, it must be trained carefully as to who is and is not allowed within its sector (i.e. “self” versus “non-self” designations). In this metaphor, vaccine technology would be equivalent to showing the guard dog a picture of a known thief and instructing it to bite said thief on sight. Of course, humans cannot ‘speak’ to the immune system, so unraveling the biochemical language by which the immune system can be ‘trained’ to attack deadly pathogens is critical to preventing epidemics. Recently, researchers at DILIsym Services Inc., Mylan Pharmaceuticals Inc., University of Nebraska, Eppley Institute for Research in Cancer and Allied Diseases, San Diego State University, and Creighton University used mal-PEG-PLA (AI050) from PolySciTech (www.polyscitech.com) to create modified nanoparticles which were decorated with an immunogenic-peptide on the outside to act as an adjuvant in vaccine technology. This research holds promise for the development of more effective vaccines against a wide range of diseases. Read more: Tallapaka, Shailendra B., Bala VK Karuturi, Pravin Yeapuri, Stephen M. Curran, Yogesh A. Sonawane, Joy A. Phillips, D. David Smith, Sam D. Sanderson, and Joseph A. Vetro. "Surface conjugation of EP67 to biodegradable nanoparticles increases the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccine after respiratory immunization and subsequent T-cell-mediated protection against respiratory infection." International Journal of Pharmaceutics (2019). https://www.sciencedirect.com/science/article/pii/S0378517319303667

“Abstract: Encapsulation of protein vaccines in biodegradable nanoparticles (NP) increases T-cell expansion after mucosal immunization but requires incorporating a suitable immunostimulant to increase long-lived memory T-cells. EP67 is a clinically viable, host-derived peptide agonist of the C5a receptor that selectively activates antigen presenting cells over neutrophils. We previously found that encapsulating EP67-conjugated CTL peptide vaccines in NP increases long-lived memory subsets of CTL after respiratory immunization. Thus, we hypothesized that alternatively conjugating EP67 to the NP surface can increase long-lived mucosal and systemic memory T-cells generated by encapsulated protein vaccines. We found that respiratory immunization of naïve female C57BL/6 mice with LPS-free ovalbumin (OVA) encapsulated in PLGA 50:50 NP (∼380 nm diameter) surface-conjugated with ∼0.1 wt% EP67 through 2 kDa PEG linkers (i.) increased T-cell expansion and long-lived memory subsets of OVA323-339-specific CD4+ and OVA257-264-specific CD8a+ T-cells in the lungs (CD44HI/CD127/KLRG1) and spleen (CD44HI/CD127/KLRG1/CD62L) and (ii.) decreased peak CFU of OVA-expressing L. monocytogenes (LM-OVA) in the lungs, liver, and spleen after respiratory challenge vs. encapsulation in unmodified NP. Thus, conjugating EP67 to the NP surface is one approach to increase the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccines after respiratory immunization. Keywords: mucosal vaccine vaccine delivery nanoparticle targeted vaccines dendritic cell targeting CD88 host-derived immunostimulant complement-derived immunostimulant”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

mPEG-PLGA from Akina used in development of Ultrasound-Triggered Neural delivery Nanoparticles

Monday, May 13, 2019, 10:14 AM ET

Neuroactive agents which are designed to have a specific effect on the brain suffer from several drawbacks. One of these is the non-specific nature of their action in which certain neural pathways are either blocked or activated regardless of location. Recently, researchers at Stanford University used mPEG-PLGA (AK090) from PolySciTech (www.polyscitech.com) to create nanoparticles that can be controlled by external ultra-sound signals. This research holds promise to enable specific delivery of compounds to discrete locations of the brain in a more controlled manner to treat a variety of disease states. Read more: Wang, Jeffrey B., Muna Aryal, Qian Zhong, Daivik B. Vyas, and Raag D. Airan. "Noninvasive Ultrasonic Drug Uncaging Maps Whole-Brain Functional Networks." Neuron 100, no. 3 (2018): 728-738. https://www.sciencedirect.com/science/article/pii/S0896627318309504

“Highlights: Ultrasound-sensitive nanoparticles enable localized drug delivery to the brain. Ultrasonic drug uncaging allows noninvasive and precise control of brain activity. Drug effects are limited to the ultrasound focus and by the kinetics of the drug. Uncaging and neuroimaging together causatively maps whole-brain functional networks. Being able to noninvasively modulate brain activity, where and when an experimenter desires, with an immediate path toward human translation is a long-standing goal for neuroscience. To enable robust perturbation of brain activity while leveraging the ability of focused ultrasound to deliver energy to any point of the brain noninvasively, we have developed biocompatible and clinically translatable nanoparticles that allow ultrasound-induced uncaging of neuromodulatory drugs. Utilizing the anesthetic propofol, together with electrophysiological and imaging assays, we show that the neuromodulatory effect of ultrasonic drug uncaging is limited spatially and temporally by the size of the ultrasound focus, the sonication timing, and the pharmacokinetics of the uncaged drug. Moreover, we see secondary effects in brain regions anatomically distinct from and functionally connected to the sonicated region, indicating that ultrasonic drug uncaging could noninvasively map the changes in functional network connectivity associated with pharmacologic action at a particular brain target. Keywords: focused ultrasound neuromodulation functional imaging functional connectivity nanotechnology drug delivery”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Akinalytics Publication Highlights PLGA Analysis Methods and Capabilities for ‘Sameness’ Determination

Thursday, May 9, 2019, 1:47 PM ET

In addition to providing for polymer products through the PolySciTech division, Akina, Inc. also provides for analysis of materials through the Akinalytics group (http://www.akinalytics.com/). A series of collaborations with the Food and Drug Administration Office of Generic Drugs have generated a great deal of data and methodology expertise in the realm of understanding the characterization of PLGA. This developed further understanding of a commonly used polymer can be applied both for formulation development as well as for establishing ‘sameness’ between a reference listed product and a proposed generic. Read more here: Kinam Park, Sarah Skidmore, Justin Hadar, John Garner, Haesun Park, Andrew Otte, Bong Kwan Soh, Gwangheum Yoon, Dijia Yu, Yeonhee Yun, Byung Kook Lee, Xiaohui Jiang (Jeff), Yan Wang. “Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation.” Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919302512

“Abstract: Injectable, long-acting depot formulations based on poly(lactide-co-glycolide) (PLGA) have been used clinically since 1989. Despite 30 years of development, however, there are only 19 different drugs in PLGA formulations approved by the U.S. Food and Drug Administration (FDA). The difficulty in developing depot formulations stems in large part from the lack of a clear molecular understanding of PLGA polymers and a mechanistic understanding of PLGA microparticles formation. The difficulty is readily apparent by the absence of approved PLGA-based generic products, limiting access to affordable medicines to all patients. PLGA has been traditionally characterized by its molecular weight, lactide:glycolide (L:G) ratio, and end group. Characterization of non-linear PLGA, such as star-shaped glucose-PLGA, has been difficult due to the shortcomings in analytical methods typically used for PLGA. In addition, separation of a mixture of different PLGAs has not been previously identified, especially when only their L:G ratios are different while the molecular weights are the same. New analytical methods were developed to determine the branch number of star-shaped PLGAs, and to separate PLGAs based on L:G ratios regardless of the molecular weight. A deeper understanding of complex PLGA formulations can be achieved with these new characterization methods. Such methods are important for further development of not only PLGA depot formulations with controllable drug release kinetics, but also generic formulations of current brand-name products. Keywords PLGA Long-acting depot L:G ratio Glucose-PLGA Star-shape Q1/Q2”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Akinalytics Publication Details PLGA-Branching Analysis Development for PLGA-Glucose/Sandostatin

Thursday, May 9, 2019, 1:45 PM ET

In addition to linear chains, polymers can be synthesized into a variety of branched configurations including star, comb, and semi-branched polymers. For several types of polymers, there are a variety of methods to measure and analyze the branching. However, no such method has existed for PLGA until just now. As part of a collaboration effort with the Food and Drug Administration Office of Generic Drugs, Akina has developed methods around GPC-4D which enable characterization of branching in branched PLGAs including PLGA-Glucose used in Sandostatin. This and other evaluation techniques are available through the Akinalytics group (http://www.akinalytics.com/). Read more: Hadar, Justin, Sarah Skidmore, John Garner, Haesun Park, Kinam Park, Yan Wang, Bin Qin, and Xiaohui Jiang. “Characterization of branched poly (lactide-co-glycolide) polymers used in injectable, long-acting formulations.” Journal of Controlled Release (2019). https://www.sciencedirect.com/science/article/pii/S0168365919302421

“Abstract: Poly(lactide-co-glycolide) (PLGA) has been used in many injectable, long-acting depot formulations. Despite frequent use of PLGA, however, its characterization has been limited to measuring its molecular weight, lactide:glycolide (L:G) ratio, and end-group. These conventional methods are not adequate for characterization of unique PLGA polymers, such as branched PLGA. Glucose-initiated PLGA (Glu-PLGA) has been used in Sandostatin® LAR Depot (octreotide acetate for injectable suspension) approved by the U.S. Food and Drug Administration (FDA) in 1998. Glu-PLGA is a branched (also known as star-shaped) polymer and determining its properties has been challenging. It is necessary to develop methods that can determine and characterize the branching parameters of Glu-PLGA. Such characterization is important not only for the quality control of formulations, but also for developing generic parenteral formulations that are required to have the same excipients in the same amount (qualitative/quantitative (Q1/Q2) sameness) as their Reference Listed Drug (RLD). In this study, an analytical technique was developed and validated using a series of branched-PLGA standards, and it was used to determine the branching parameters of Glu-PLGA extracted from Sandostatin LAR, as well as Glu-PLGAs obtained from three different manufacturers. The analytical technique was based on gel-permeation-chromatography with quadruple detection systems (GPC-4D). GPC-4D enabled characterization of Glu-PLGA in its concentration, absolute molecular weight, hydrodynamic radius and intrinsic viscosity. The plot of the branch units per molecule as a function of molar mass provides a unique profile of each branched PLGA. The Mark-Houwink plots were also used to distinguish different Glu-PLGAs. These ensemble identification methods indicate that the branch units of Glu-PLGAs extracted from Sandostatin LAR range from 2 (i.e., linear) at the lower end of the molecular weight to <4 br="" branched="" depot="" for="" glu-plga.="" keywords:="" long-acting="" majority="" of="" plga="" q1="" sameness="" sandostatin="" star-shape="" the="">
Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

mPEG-PLGA from PolySciTech used in development of peptide-loaded nanoparticles to treat bone-disease

Tuesday, May 7, 2019, 4:11 PM ET

Normal human bone is in a constant state of growth and remodeling by a balance between osteoblasts (which grow new bone) and osteoclasts (which remove old bone). Several bone-diseases (osteoporosis and others) involve an imbalance in these processes where bone is resorbed in an unhealthy manner. Recently, researchers at University of Maryland used mPEG-PLGA (AK010) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a newly developed peptide-based medicine that reduces bone resorption process. This research holds promise to provide for improved therapies against a variety of diseases which attack bone. Read more: Sunipa Majumdar, Aniket S. Wadajkar, Hanan Aljohani, Mark A. Reynolds, Anthony J. Kim, and Meenakshi Chellaiah “Engineering of L-Plastin Peptide-Loaded Biodegradable Nanoparticles for Sustained Delivery and Suppression of Osteoclast Function In Vitro” International Journal of Cell Biology Volume 2019, Article ID 6943986, 13 pages https://doi.org/10.1155/2019/6943986

“Abstract: We have recently demonstrated that a small molecular weight amino-terminal peptide of L-plastin (10 amino acids; “MARGSVSDEE”) suppressed the phosphorylation of endogenous L-plastin. Therefore, the formation of nascent sealing zones (NSZs) and bone resorption are reduced. The aim of this study was to develop a biodegradable and biocompatible PLGA nanocarrier that could be loaded with the L-plastin peptide of interest and determine the efficacy in vitro in osteoclast cultures. L-plastin MARGSVSDEE (P1) and scrambled control (P3) peptide-loaded PLGA-PEG nanoparticles (NP1 and NP3, respectively) were synthesized by double emulsion technique. The biological effect of nanoparticles on osteoclasts was evaluated by immunoprecipitation, immunoblotting, rhodamine-phalloidin staining of actin filaments, and pit forming assays. Physical characterization of well-dispersed NP1 and NP3 demonstrated ~130-150 nm size, < 0.07 polydispersity index, ~-3 mV ζ-potential, and a sustained release of the peptide for three weeks. Biological characterization in osteoclast cultures demonstrated the following: NP1 significantly reduced (a) endogenous L-plastin phosphorylation; (b) formation of NSZs and sealing rings; (c) resorption. However, the assembly of podosomes which are critical for cell adhesion was not affected. L-plastin peptide-loaded PLGA-PEG nanocarriers have promising potential for the treatment of diseases associated with bone loss. Future studies will use this sustained release of peptide strategy to systematically suppress osteoclast bone resorption activity in vivo in mouse models demonstrating bone loss.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA-NHS from PolySciTech used in Development of Prodrug Nanoparticles for Drug-Delivery to Cancer

Friday, May 3, 2019, 10:13 AM ET

One method of loading drugs into a polymer, beyond simple encapsulation, is to actively conjugate the drug to the end or side-chains of the polymer so that it is bound by a cleavable linkage. Such a design is called a ‘prodrug’ in that it breaks down to release the drug in the human body. In organic chemistry, N-hydroxysuccinimide ester serves as an effective ‘leaving group’ when enables these kinds of attachments to occur between a carboxylic acid and a nucleophile (typically an amine). One of the products PolySciTech Provides is PLGA-NHS, this is a degradable PLGA chain with the acid endcap activated into the NHS-ester form such that it is ready to conjugate to a nucleophile. Recently, researchers at Los Gatos Pharmaceuticals, Inc Used PLGA-NHS (AI096) from PolySciTech (www.polyscitech.com) to create drug-conjugate (Prodrug) and form this into nanoparticles. This research holds promise to provide for superior drug delivery formulations which may be effective for cancer therapy. Read more: Langecker, Peter, Matthias Steiert, Toshiaki Hino, Jan Scicinski, and Kumarapandian Paulvannan. "Composite Nanoparticles And Uses Thereof." U.S. Patent Application 16/026,446, filed December 27, 2018. https://patents.google.com/patent/US20180369232A1/en

“Abstract: Provided herein are composite nanoparticles, methods of making composite nanoparticles and methods of using composite nanoparticles to treat or ameliorate various diseases, such as, for example, cancer. (Synopsis from Background/Summary): What is needed are nanoparticles large enough for selective tumor tissue penetration (diameter of between 60 and 400 nm) which can decompose within the tissue to a size amenable for cellular uptake (diameter of less than about 20 nm) by tumor cells. The above concept may have broad applicability beyond selective delivery of active ingredients to tumor tissues. The present invention satisfies these and other needs by providing in one aspect, a composite nanoparticle. The composite nanoparticle includes subunit nanoparticles of between about 10 nm and about 20 nm diameter which contain an active ingredient, wherein the composite nanoparticle has a diameter of between about 60 nm and about 400 nm. In another aspect, a method for forming composite nanoparticles is provided. Subunit nanoparticles of diameter between about 10 nm and about 20 nm which include an active ingredient are synthesized and assembled into composite nanoparticles of diameter between about 60 nm and about 400 nm.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PEG-PLA from PolySciTech used in development of polymersomes to cross the blood-brain-barrier.

Tuesday, April 30, 2019, 11:47 AM ET

The brain is a difficult organ to deliver drugs to as it protects itself via the highly selective ‘blood-brain-barrier’ which is very difficult for medicines to cross. Recently, researchers at Kent State used mPEG-PLA (AK031) and mPEG-PLA-fluorescent (AV035) from PolySciTech (www.polyscitech.com) to develop polymersomes to cross the blood-brain barrier. This research holds promise to enable the treatment of many diseases which affect brain tissue. Read more: Manickavasagam, Dharani. "Preparation and Characterization of Polymersomes for Nose-to-Brain Delivery of Combination Therapeutics in Neuroinflammation Treatment." PhD diss., Kent State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=kent1555522694193999

“Abstract: Neuroinflammation, a hallmark of many neurodegenerative diseases is mediated by microglia, the primary immune cells of the central nervous system (CNS). Activated microglial cells respond to neuronal injury and remove cellular debris, infectious agents via phagocytosis conferring neuroprotection. However, the chronic activation of these cells impairs neuronal function through the excessive release of NO and proinflammatory cytokines TNF-α and interleukins (IL-6, IL-1β and IL-12) which contributes to neuroinflammation and subsequent neurodegeneration in the brain. Thus, suppressing microglial activation is an effective therapeutic strategy to combat neuroinflammation associated with degenerative brain diseases. While anti-inflammatory agents are required to treat neurodegeneration, they may not be sufficient on their own as the disorder is multifaceted and complex but may be effective as part of a combination therapy. Therefore, improved treatment options focused on combinatory neuroprotective effects of simvastatin (Sim) and brain derived neurotrophic factor (BDNF), seem most beneficial in restoring CNS damage, as Sim is known to inhibit inflammation, promote cell survival and BDNF is a predominant neurotrophic factor that mediates survival and growth of a variety of neurons in the CNS. However, the delivery of combination therapeutics that hold promise for the treatment of neurological disorders lack clinical efficacy due to their inability in reaching high enough concentrations in the brain primarily due to the blood brain barrier (BBB), blood-cerebrospinal fluid (CSF) barrier, presence of efflux systems, enzymatic degradation, and several other factors such as rapid clearance from circulation and off-target effects. This calls for the need to develop an efficient drug delivery system (DDS) to overcome obstacles that impede CNS drug delivery and alternate approaches to bypass the BBB. Since microglia function as macrophages, the DDS must be also be effectively removed after the drug has been delivered to prevent the activation of microglial cells. Thus, biocompatible nano-sized delivery systems that specifically target pathways involved in microglial activation and eliminated via natural pathways in the body shows suitability and promise in treatment of neuroinflammation associated with neurodegeneration. The multiple challenges associated with brain drug delivery prompted the proposed investigation. Nano-sized systems (polymeric vesicles) such as polymersomes composed of bilayer membrane will be a suitable platform as they provide dual aqueous compartments that can store and deliver hydrophilic (BDNF) and hydrophobic (Sim) drugs. Therefore, the objective of this research work is to design and characterize polymersomes using diblock copolymers PEG-PLA (polyethylene glycol-polylactic acid) and evaluate its suitability for intranasal delivery of dual neuroprotective drugs (Sim/BDNF), in inhibiting microglial mediated inflammatory responses and protecting toxic environment surrounding neurons in LPS-induced animal model of neuroinflammation. The proposed project is attempting to tackle obstacles associated with drug delivery in CNS disorders. Given that, PEG-PLA is biocompatible, biodegradable, physiologically well tolerated and has low immunogenicity, this work provides preliminary evidence for the application of polymersomes to effectively deliver combination drugs to the brain via the non-invasive nasal route to bypass the BBB.”

Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA-Rhodamine from PolySciTech used in research on Pickering emulsion Stabilization by biodegradable nanoparticles

Monday, April 29, 2019, 11:22 AM ET

A Pickering emulsion is an emulsion that is stabilized by solid particles which adsorb onto the interface between the two phases. Nanoparticles comprised of PLGA and of a small enough size could potentially be used for this application. The primary advantage of using PLGA nanoparticles for this application is that the formed emulsion would be comprised of biodegradable and biocompatible materials which can have an advantage in terms of use in pharmaceutical and cosmetological applications. Recently, researchers at Université Paris-Saclay (France) utilized rhodamine conjugated PLGA (AV011) from PolySciTech (www.polyscitech.com) to track nanoparticles during the formation of pickering emulsions stabilized with PLGA nanoparticles under varying conditions. This research holds promise for improved formation of biocompatible emulsions for a wide range of uses. Read more: Albert, Claire, Nicolas Huang, Nicolas Tsapis, Sandrine Geiger, Veěronique Rosilio, Ghozlene Mekhloufi, David Chapron et al. "Bare and sterically stabilized PLGA nanoparticles for the stabilization of Pickering emulsions." Langmuir 34, no. 46 (2018): 13935-13945. https://pubs.acs.org/doi/abs/10.1021/acs.langmuir.8b02558

“Pickering emulsions were formulated using biodegradable and biocompatible poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) prepared without surfactants or any other polymer than PLGA. A pharmaceutical and cosmetic oil (Miglyol) was chosen as the oil phase at a ratio of 10% w/w. These emulsions were then compared with emulsions using the same oil but formulated with well-described PLGA-poly(vinyl alcohol) (PVA) NPs, i.e., with PVA as NP stabilizers. Strikingly, the emulsions demonstrated very different structures at macroscopic, microscopic, and interfacial scales, depending on the type of NPs used. Indeed, the emulsion layer was significantly thicker when using PLGA NPs rather than PLGA-PVA NPs. This was attributed to the formation and coexistence of multiple water-in-oil-in-water (W/O/W) and simple oil-in-water (O/W) droplets, using a single step of emulsification, whereas simple O/W emulsions were obtained with PLGA-PVA NPs. The latter NPs were more hydrophilic than bare PLGA NPs because of the presence of PVA at their surface. Moreover, PLGA NPs only slightly lowered the oil/water interfacial tension whereas the decrease was more pronounced with PLGA-PVA NPs. The PVA chains at the PLGA-PVA NP surface could probably partially desorb from the NPs and adsorb at the interface, inducing the interfacial tension decrease. Finally, independent of their composition, NPs were adsorbed at the oil/water interface without influencing its rheological behavior, possibly due to their mobility at their interface. This work has direct implications in the formulation of Pickering emulsions and stresses the paramount influence of the physicochemical nature of the NP surface into the stabilization of these systems.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in development of nanoparticle vaccine delivery system to prevent Johne’s disease in cattle

Wednesday, April 24, 2019, 1:33 PM ET

In addition to human applications, PLGA from PolySciTech is also used in veterinary uses. Johne’s disease, caused by Mycobacterium avium subspecies paratuberculosis, is a contagious, chronic, and usually fatal infection that affects primarily the small intestine of ruminants. Killing this bacteria is difficult and this contagious disease can spread rapidly through a herd with devastating financial effects to farmers as well as reducing the overall food supply. Recently, researchers at Washington State University, US Department of Agriculture, Alexandria University (Egypt), Egyptian Ministry of Agriculture, and Inje University (Korea) utilized PLGA (AP054) from PolySciTech (www.polyscitech.com) to create vaccine-loaded nanoparticles for prevention of Johne’s disease. This research holds promise to prevent this rapidly spreading and fatal disease from affecting cattle and improve food sustainability and security. Read more: Abdellrazeq, Gaber S., Mahmoud M. Elnaggar, John P. Bannantine, David A. Schneider, Cleverson D. Souza, Julianne Hwang, Asmaa HA Mahmoud et al. "A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis." Vaccine (2019). https://www.sciencedirect.com/science/article/pii/S0264410X19305043

“Highlights: A M. a. sbsp. paratuberculosis membrane protein elicits CD8 T cells that kill intracellular Map. Incorporation of MMP into a nanoparticle (NP) vector enhances intracellular killing of Map. Intracellular killing of M. a. sbsp. paratuberculosis is mediated by CD8 T cells.Abstract: Recent efforts to develop a live attenuated vaccine against Mycobacterium avium subsp. paratuberculosis (Map), the causative agent of Johne’s disease (JD), revealed relA is important in Map virulence. Deletion of the relA gene impairs the ability of Map to establish a persistent infection. Analysis of the basis for this observation revealed infection with a relA deletion mutant (ΔrelA) elicits development of cytotoxic CD8 T cells (CTL) with the ability to kill intracellular bacteria. Further analysis of the recall response elicited by ΔrelA vaccination showed a 35 kDa membrane peptide (MMP) is one of the targets of the immune response, suggesting it might be possible to develop a peptide-based vaccine based on MMP. To explore this possibility, ex vivo vaccination studies were conducted with MMP alone and incorporated into a nanoparticle (NP) vector comprised of poly (D, L-lactide-co-glycolide) and monophosphoryl lipid A (PLGA/MPLA). As reported, ex vivo vaccination studies showed CD8 CTL were elicited with classic and monocyte derived dendritic cells (cDC and MoDC) pulsed with MMP alone and incorporated into a PGLA/MPLA vector. Incorporation of MMP into a NP vector enhanced the ability of CD8 CTL to kill intracellular bacteria. The findings indicate incorporation of MMP into a PGLA/MPLA nanoparticle vector is one of the possible ways to develop a MMP based vaccine for Johne’s disease. Keywords: Zoonotic pathogen Mycobacterium avium subspecies paratuberculosis Propidium monoazide Flow cytometry Intracellular killing Monocyte derived dendritic cells Cytotoxic T cells Bovine”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

BPCR News Release

Thursday, April 18, 2019, 3:21 PM ET


Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

P(DL)La-PEG-COOH and mPEG-PLA from PolySciTech used in development of antibacterial-nanovesicles to treat MRSA

Thursday, April 18, 2019, 2:45 PM ET

Typical staphylococcus aureus (Staph) is an extremely common bacterial present on skin and hair in up to 25 percent of healthy people. Typical Staph is easily treated with conventional antibiotics, however Methicillin-Resistant Staphylococcus aureus (MRSA) is an antibiotic resistant strain that has evolved to be difficult to treat. Conventional therapies work poorly against this kind of bacterial infection and these often require advanced solutions to prevent the spread of the difficult-to-kill bacteria. Recently, researchers at Northeastern University used PLA-PEG-COOH (AI023) and mPEG-PLA (AK021) from PolySciTech (www.polyscitech.com) to develop bacteria-killing nanovesicles to treat MRSA. This research holds promise to provide for treatment against this difficult to treat bacterial infection. Read more: Bassous, Nicole J., and Thomas J. Webster. "The Binary Effect on Methicillin‐Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline‐Rich Amino Acid Sequences and Inorganic Nanoparticles." Small (2019): 1804247. https://onlinelibrary.wiley.com/doi/abs/10.1002/smll.201804247

“Abstract: Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic‐resistant bacterial infections, especially those caused by methicillin‐resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self‐assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano‐PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver‐to‐AMP of about 1:5.8 corresponding to ≈11.6 µg mL−1 of silver nanoparticles and 14.3 × 10−6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Block-copolymers from PolySciTech used in development of Adapalene-nanoparticle delivery system to cross the blood-brain-barrier

Thursday, April 18, 2019, 2:43 PM ET

“Drugs don’t deliver themselves” is a statement which has multiple meanings depending on who you are talking to. For retinoid molecules, drug-delivery to brain tissue is not a simple task as these highly-effective therapeutics are also highly water insoluble. Furthermore, the brain has extremely selective uptake of molecules across the ‘blood-brain-barrier’ which means any attempt to deliver a medicinal molecule to the brain will require getting the molecule across this barrier so that it can have therapeutic efficacy. Recently, researchers at Barrow Neurological Institute and University of Texas Health Science Center at Houston used PCL (AP108) and mPEG-PLA (AK054) from PolySciTech (www.polyscitech.com) to create adapalene loaded nanoparticles for brain-delivery. This research holds promise to provide for improved therapy against a variety of neurological diseases. Read more: Medina, David X., Eugene P. Chung, Robert Bowser, and Rachael W. Sirianni. "Lipid and polymer blended polyester nanoparticles loaded with adapalene for activation of retinoid signaling in the CNS following intravenous administration." Journal of Drug Delivery Science and Technology (2019). https://www.sciencedirect.com/science/article/pii/S1773224719300358

“Abstract: Small molecule retinoids are potential therapeutics for a variety of neurological diseases. However, most retinoids are poorly water soluble and difficult to deliver in vivo, which prevents further study of their utility to treat disease. Here, we focus on adapalene, an FDA approved drug that is a specific agonist for the retinoic acid receptor β (RARβ). We sought to develop nanoparticle delivery systems that would enable effective drug delivery to the CNS. We developed strategies to produce nanoparticles based on the hypothesis that incorporation of hydrophobic molecules into a polyester base would improve adapalene loading. In the first scheme, poly (lactic acid)-poly (ethylene glycol) (PLA-PEG) was blended with low molecular weight poly (lactic acid) (PLA) or poly (caprolactone) (PCL). In the second scheme, poly (lactic-co-glycolic acid) (PLGA) was blended with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol) (DSPE-PEG). Our data demonstrate that blending low molecular weight polyesters or DSPE-PEG into the primary nanoparticle base improves encapsulation of adapalene, presumably by enhancing adapalene solubility in the nanoparticle. Peripheral administration of these nanoparticles activated retinoid signaling in the brain and spinal cord of healthy mice. These studies provide new approaches for nanoparticle fabrication and establish proof of principle that systemically administered, adapalene-loaded nanoparticles activate retinoid signaling in the CNS.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLLA-PEG-Mal and PLGA-Rhodamine from PolySciTech used in development of tumor-seeking nanoparticle-laden stem-cell drug delivery system for treatment of cancer.

Friday, April 12, 2019, 2:59 PM ET

Cancer is unlike other diseases in that it is not caused by an invasion from a foreign pathogen (such as bacterial or viral infection). The inherent difficulty with its treatment is that, since cancer is comprised of cells similar to that of the patient’s own cells, most therapies which are applied to kill the cancer also harm the patient. This lack of specificity is the main cause of side-effects from chemotherapy (hair-loss, naseua, weakness, etc.). One mechanism to deal with this is to design a delivery system which will ensure that the bulk of the cancer treatment goes to the site of the tumor. Recently, researchers at University of Minnesota and Breck School utilized PLGA-rhodamine (AV011) and PLLA-PEG-Mal (AI119 ) from PolySciTech (www.polyscitech.com) to develop TAT functionalized nanoparticles for uptake into MSC’s to deliver to tumors. This research holds promise to provide for improved treatments of cancer. Read more: Moku, Gopikrishna, Buddhadev Layek, Lana Trautman, Samuel Putnam, Jayanth Panyam, and Swayam Prabha. "Improving Payload Capacity and Anti-Tumor Efficacy of Mesenchymal Stem Cells Using TAT Peptide Functionalized Polymeric Nanoparticles." Cancers 11, no. 4 (2019): 491. https://www.mdpi.com/2072-6694/11/4/491

“Abstract: Mesenchymal stem cells (MSCs) accumulate specifically in both primary tumors and metastases following systemic administration. However, the poor payload capacity of MSCs limits their use in small molecule drug delivery. To improve drug payload in MSCs, we explored polymeric nanoparticles that were functionalized with transactivator of transcription (TAT) peptide. Paclitaxel loaded poly(DL-lactide-co-glycolide) (PLGA) nanoparticles (15–16% w/w paclitaxel; diameter of 225 ± 7 nm; and zeta potential of −15 ± 4 mV) were fabricated by emulsion-solvent evaporation method, followed by TAT-conjugation to the surface of nanoparticles via maleimide-thiol chemistry. Our studies demonstrated that TAT functionalization improved the intracellular accumulation and retention of nanoparticles in MSCs. Further, nano-engineering of MSCs did not alter the migration and differentiation potential of MSCs. Treatment with nano-engineered MSCs resulted in significant (p < 0.05) inhibition of tumor growth and improved survival (p < 0.0001) in a mouse orthotopic model of lung cancer compared to that with free or nanoparticle encapsulated drug. In summary, our results demonstrated that MSCs engineered using TAT functionalized nanoparticles serve as an efficient carrier for tumor specific delivery of anticancer drugs, resulting in greatly improved therapeutic efficacy. Keywords: mesenchymal stem cells (MSCs); TAT peptide; PLGA; paclitaxel; nano-engineered MSCs; orthotopic lung tumor model”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA-PEG-PLGA from PolySciTech used in development of Propranolol delivery system for treatment of hemangioma

Friday, April 12, 2019, 2:56 PM ET

Hemangioma’s are a common form of a birth mark consisting of an area with an excess of blood-vessels. In the case of superficial surface hemangioma’s there may be no need for treatment as these are benign and heal over time. However, hemangioma’s can occur anywhere and if they are present in certain internal organs (for example brain or liver) or if they interfere with vision or breathing, they can be serious. Recently, researchers at Zhengzhou University (China) used PLGA-PEG-PLGA (AK016) from PolySciTech (www.polyscitech.com) to create propranolol loaded drug-delivery particles. This research holds promise to provide for improved therapy against hemangiomas. Read more: Guo, Xiaonan, Changxian Dong, Qiuyu Liu, Xiaoshuang Zhu, Song Zuo, and Hongyu Zhang. "The sustained and targeted treatment of hemangiomas by propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres." Biomedicine & Pharmacotherapy 114 (2019): 108823. https://www.sciencedirect.com/science/article/pii/S0753332219306535

“Highlights: Propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM) realized sustained therapy of hemangiomas. PCLIM could inhibit the proliferation of HemSCs and expression of VEGF and bFGF in HemSCs. PCLIM could realize the targeted therapy of hemangiomas by targeting CD133-positive hemangioma-derived stem cells. Abstract: We previously developed propranolol-encapsulated liposomes-in-microspheres (PLIM) to realize the sustained propranolol release for the treatment of hemangiomas. However, the liposomes released from the microspheres still lacked specificity for CD133-positive hemangioma-derived stem cells (HemSCs) which are considered to be the seeds of hemangiomas. Therefore, we hereby encapsulated propranolol-loaded CD133 aptamers conjugated liposomes in poly(lactic-co-glycolic acid (PLGA) microspheres to develop propranolol-loaded CD133 aptamers conjugated liposomes-in-microspheres (PCLIM), to realize the aim of the sustained and targeted therapy of hemangiomas. The evaluation of the release of propranolol from PCLIM was carried out, and the cytotoxic effect and angiogenic growth factor expression inhibitory ability of PCLIM were performed in HemSCs. The in vivo hemangioma inhibitory ability of PCLIM was also investigated in nude mice with subcutaneous human hemangiomas. PCLIM possessed a desired size of 29.2 μm, drug encapsulation efficiency (25.3%), and a prolonged drug release for 40 days. Importantly, PCLIM could inhibit HemSCs proliferation and the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor-A (VEGF) in HemSCs to a greater extent compared with PLIM. In nude mice bearing hemangioma xenograft, PCLIM showed the best therapeutic efficacy towards hemangiomas, as reflected by remarkably decreased hemangioma volume, weight and microvessel density (MVD). Thus, our results demonstrated that PCLIM realized the sustained and targeted treatment of hemangiomas, resulting in remarkable inhibition of hemangiomas. Keywords: CD133 Hemangiomas Propranolol Liposomes Microspheres Sustained release”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA-PEG-COOH from PolySciTech used in development of nanoparticle-based anticoagulant (Alteplase) delivery system for treatment of blood clotting

Thursday, April 11, 2019, 2:39 PM ET

The formation of blood-clots within the human blood system is part of several severe diseases including heart-attack and stroke. Alteplase is a is a tissue plasminogen activator which acts to break up these clots. To improve the efficiency and specificity of this action, the Alteplase can be encapsulated in nanoparticles decorated with a plaque-homing peptide, CREKA, which binds to fibrin-fibronectin clots and accumulates at the surface of plaques. Recently, Researchers at Universidad de Sevilla (Spain) used PLGA-PEG-COOH (AI034) from PolySciTech (www.polyscitech.com) to develop drug-delivery nanoparticles carrying Alteplase. This research holds promise to provide for improved treatments of diseases associated with clotting such as stroke and heart-attacks. Read more: Fernández Pérez, Irene. "Estudio preliminar de una formulación de Nanoparticulaspara targetactivo de un." Thesis Presentation Universidad de Sevilla (2018). https://idus.us.es/xmlui/bitstream/handle/11441/82199/Irene%20Fern%C3%A1ndez%20P%C3%A9rez.pdf?sequence=1

“Abstract [*translated*]: The present work fits into the currently emerging field of nanomedicine. Specifically, it is a preliminary study based in the design and development of nanoparticles that will serve as a system of administration of a fibrinolytic drug, which is intended to actively address the pathological thrombi formed by the process of blood coagulation. To do this, several batches of PLGA nanoparticles have been synthesized using different polymers (Resomer® 504H and PLGA-PEG) and varying amounts/concentration of drug (Actilyse®). Nanoparticle synthesis has been carried out by the double emulsion method with evaporation of solvent, obtaining particles of an adequate nanometric size (~ 200 - 300 nm) with narrow size distribution and negative zeta potential. The tests carried out on the efficacy of drug encapsulation presented good results. The maximum loading efficiency (97%) was observed for PLGA-PEG particles loaded at 5% w / w (active / polymer). To carry out the preliminary study of the design of these nanoparticles for the targeting of clots, the CREKA pentapeptide was used for surface functionalization of the particles. This enables a process of bioconjugation. This lead to a slight increase in the average size of the particles and in the PdI values. The surface load data obtained showed a potentially better conjugation efficiency for the PLGA-PEG particles. However, this bioconjugation data is very preliminary.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PolySciTech PLGA used in development of magnetic nanoparticles for breast-cancer therapy

Tuesday, April 9, 2019, 3:33 PM ET

There are many ways to control motion of nanoparticles in a living body including both active and passive targeting. Another method is to generate nanoparticles which respond to an external stimulus such as magnetism which can be used to draw nanoparticles into a target region of the body near a tumor. Recently, Researchers at Purdue University used PLGA (AP020) From PolySciTech (www.polyscitech.com) to develop paclitaxel-loaded nanoparticles and tested these for their effects on breast cancer. This research holds promise to provide for improved therapies against this form of cancer. Read more: Park, Jinho, Joonyoung Park, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Magnetophoretic delivery of a tumor priming agent for chemotherapy of metastatic murine breast cancer." Molecular pharmaceutics (2019). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01148

“Tumor microenvironment (TME) is a significant physical barrier to effective delivery of chemotherapy into solid tumors. To overcome this challenge, tumors are pre-treated with an agent that reduces cellular and extracellular matrix densities prior to chemotherapy. However, it also comes with a concern that metastasis may increase due to the loss of protective containment. We hypothesize that timely priming at the early stage of primary tumors will help control metastasis. To test this, we primed orthotopic 4T1 breast tumors with a paclitaxel (PTX)-loaded iron oxide decorated poly(lactic-co-glycolic acid) nanoparticle composite (PTX@PINC), which can be quickly concentrated in target tissues with the aid of an external magnet, and monitored its effect on the delivery of subsequently administered NPs. Magnetic resonance imaging and optical whole-body imaging confirmed that PTX@PINC was efficiently delivered to tumors by the external magnet and help loosen the tumors to accommodate subsequently-delivered NPs. Consistently, the primed tumors responded to Doxil better than non-primed tumors. In addition, lung metastasis was significantly reduced in the animals PINC-primed prior to Doxil administration. These results support that PINC combined with magnetophoresis can facilitate timely management of primary tumors with a favorable secondary effect on metastasis.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Fluorescent PLGA from PolySciTech used in development of wearable biomedical sensing system

Tuesday, April 9, 2019, 3:32 PM ET

For chronic illness and other applications the convenience and ease of a wearable device (such as a transdermal patch or a wrist-watch type device) provides for several advantages over continuous monitoring and manual medicinal administrations. Recently, researchers at Griffith University, Berghofer Medical Research Institute, and University of South Australia, used fluorescent PLGA-AF488 (custom-made) from PolySciTech (www.polyscitech.com) as part of a wearable smart-device to control drug delivery in response to changes in mechanical forces such as changes in pulse or other factors. This research holds promise for the development of devices for use in a wide array of disease states. Read more: Shi, Ge, Tianqing Liu, Zlatko Kopecki, Allison Cowin, Ivan Lee, Jing-Hong Pai, Sean E. Lowe, and Yu Lin Zhong. "A Multifunctional Wearable Device with a Graphene/Silver Nanowire Nanocomposite for Highly Sensitive Strain Sensing and Drug Delivery." Journal of Carbon Research C 5, no. 2 (2019): 17. https://www.mdpi.com/2311-5629/5/2/17

“Abstract: Advances in wearable, highly sensitive and multifunctional strain sensors open up new opportunities for the development of wearable human interface devices for various applications such as health monitoring, smart robotics and wearable therapy. Herein, we present a simple and cost-effective method to fabricate a multifunctional strain sensor consisting of a skin-mountable dry adhesive substrate, a robust sensing component and a transdermal drug delivery system. The sensor has high piezoresisitivity to monitor real-time signals from finger bending to ulnar pulse. A transdermal drug delivery system consisting of polylactic-co-glycolic acid nanoparticles and a chitosan matrix is integrated into the sensor and is able to release the nanoparticles into the stratum corneum at a depth of ~60 m. Our approach to the design of multifunctional strain sensors will lead to the development of cost-effective and well-integrated multifunctional wearable devices. Keywords: graphene; silver nanowire; multifunctional; wearable; strain sensor; drug delivery”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Poly(lactide)-diacrylate from PolySciTech used in patent describing development of advanced assay method

Tuesday, April 9, 2019, 3:31 PM ET

The ability to rapidly and accurately diagnose a disease state in a patient is critical as this guides the subsequent routes of treatment. A recent patent by Selux Diagnostics Inc. describes the use of PLA-diacrylate (AI036) from PolySciTech (www.polyscitech.com) to develop particles for assay applications. This research holds promise for improved assay methodologies across a wide array of applications including diagnostic applications. Read more: Stern, Eric, Aleksandar Vacic, Alec Nathanson Flyer, Benjamin Spears, and Susan Clardy. "Dissociable nanoparticles with inter alia transition-metal complex catalysts." U.S. Patent Application 15/745,361, filed March 28, 2019. https://patents.google.com/patent/US20190091673A1/en

“Abstract: Nanoparticles for use in assay methods for detecting analytes in samples, which comprise a signal inducing agent, e.g. a transition-metal catalyst or a chemiluminophore, a chemiluminophore precursor, a soluble absorber, or a soluble absorber precursor. After binding to an analyte, the nanoparticle is dissociated by a chemical or physical trigger, e.g. an organic solvent or ultrasound, to release the signal inducing agent, which releases a detectable signal via a physical or chemical reaction. The nanoparticles comprising a chemiluminophore, a chemiluminophore precursor, a soluble absorber, or a soluble absorber precursor can also effect chemical reactions that serve as signal amplifiers.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PEG-block copolymers from PolySciTech used in development of ultra-sound triggered nanoparticles for localized drug delivery

Thursday, March 28, 2019, 1:37 PM ET

The same molecule which operates as a medicine in one part of the body may be highly toxic in another part of the body. For this reason, the ability to control the delivery of a molecule to a very specific area is highly preferential for a wide variety of diseases. One means to do this is to introduce the medicinal molecule in a bound form and then externally trigger it by a specific mechanism so that it is only unbound in a specific region. Recently, researchers from Stanford University, University of California, Massachusetts Institute of Technology, and Massachusetts General Hospital used mPEG-PLGA, mPEG-PLA, and mPEG-PCL (AK073, AK001, AK003, AK004, AK052, AK090) from PolySciTech (www.polyscitech.com) to generate ultra-sound triggered nanoparticles. This research holds promise to provide for localized drug delivery. As a side-note, co-author Ananya Karthik, a high-school student and Regeneron Science Talent Search finalist, qualifies as one of the youngest scientists to ever author a paper utilizing PolySciTech polymers. Read more: Zhong, Qian, Byung C. Yoon, M. Aryal, Jeffrey B. Wang, T. Ilovitsh, M. A. Baikoghli, N. Hosseini-Nassab, A. Karthik, R.H. Cheng, K.W. Ferrara, R.D. Airan "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." Biomaterials (2019). https://www.sciencedirect.com/science/article/pii/S0142961219301656

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness and relatively broad drug spatial distribution. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body with high spatial and temporal precision. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle meet these needs, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs, beyond a few niche applications. Here, we develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted delivery of hydrophobic drugs with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that are scalable and yield sterile, stable, and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, we exhibit a new potential application of these nanoemulsions for local control of vascular tone. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for efficacious, noninvasive, and localized ultrasonic drug uncaging for myriad targets in the brain and body. Keywords: Focused ultrasound Clinically translatable Targeted drug delivery Noninvasive ultrasonic drug uncaging Drug delivery platform Spatiotemporally controlled release.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

PLGA from PolySciTech used in Patent Describing Complex Microdevice Manufacture

Thursday, March 28, 2019, 1:35 PM ET

Manufacturing techniques are constantly in a state of development and there have been several recent advances in development of construction of very small and very complicated parts. Often such parts are too miniscule in size for conventional machining techniques to be of much use which requires innovation in manufacturing techniques. Recently, researchers from Massachusetts Institute of Technology used PLGA (AP045) from PolySciTech (www.polyscitech.com) as part of their patent application for complex microdevices created by a combination of photolithography and micromachining techniques. This research could be used to generated a wide array of microdevices for biomedical applications. Read more: Mchugh, Kevin, Ana Jaklenec, and Robert S. Langer. "Microdevices With Complex Geometries." U.S. Patent Application 16/130,368, filed March 14, 2019. http://www.freepatentsonline.com/y2019/0076631.html

“Abstract: Microdevices with complex three-dimensional (3D) internal and external structures are described. The microdevices are made by a method combining micromolding and soft lithography with an aligned sintering process. The microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), generates microdevices with complex geometries and with fully-enclosed internal cavities containing a solid or liquid. The microdevices are useful for biomedical, electromechanical, energy and environmental applications.”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

mPEG-PLGA/PLGA from PolySciTech used in development of dual-drug loaded nanoparticle-based brain-cancer therapy

Thursday, March 21, 2019, 4:16 PM ET

Glioblastoma is a form of brain cancer in which malignant glial cells spread to various areas of the brain. This form of cancer is very difficult to treat and requires specific manipulations of the biochemistry of the malignant cells to kill them. Gefitinib acts to dephosphorylate Bcl-2 associated death promoter (BAD) and GSK461364A induces cell cycle arrest at G2/M phase. Both of these mechanisms lead to apoptosis (cell death) and together these drugs can act synergistically to be potent treatment against cancer. Recently, researchers at University of Massachusetts Lowell utilized mPEG-PLGA (AK027) and PLGA (AP023) from PolySciTech (www.polyscitech.com) to create dual-loaded nanoparticles and tested these for use as a treatment against glioblastoma. This research holds promise to provide new therapeutic options against this lethal form of cancer. Read more: Velpurisiva, Praveena, and Prakash Rai. "Synergistic Action of Gefitinib and GSK41364A Simultaneously Loaded in Ratiometrically-Engineered Polymeric Nanoparticles for Glioblastoma Multiforme." Journal of Clinical Medicine 8, no. 3 (2019): 367. https://www.mdpi.com/2077-0383/8/3/367

“Abstract: Glioblastoma Multiforme is a deadly cancer of glial cells with very low survival rates. Current treatment options are invasive and have serious side effects. Single drug treatments make the tumor refractory after a certain period. Combination therapies have shown improvements in treatment responses against aggressive forms of cancer and are becoming a mainstay in the management of cancer. The purpose of this study is to design a combinatorial treatment regimen by engineering desired ratios of two different small molecule drugs (gefitinib and GSK461364A) in a single carrier that can reduce off-target effects and increase their bioavailability. Synergistic effects were observed with our formulation when optimal ratios of gefitinib and GSK461364A were loaded in poly (lactic-co-glycolic) acid and polyethylene glycol (PLGA-PEG) nanoparticles and tested for efficacy in U87-malignant glioma (U87-MG) cells. Combination nanoparticles proved to be more effective compared to single drug encapsulated nanoparticles, free drug combinations, and the mixture of two single loaded nanoparticles, with statistically significant values at certain ratios and drug concentrations. We also observed drastically reduced clonogenic potential of the cells that were treated with free drugs and nanoparticle combinations in a colony forming assay. From our findings, we conclude that the combination of GSK461364A and higher concentrations of gefitinib when encapsulated in nanoparticles yield synergistic killing of glioma cells. This study could form the basis for designing new combination treatments using nanoparticles to deliver multiple drugs to cancer cells for synergistic effects. Keywords: combination therapy; cancer; glioblastoma multiforme; polymeric nanoparticles; gefitinib; GSK461364A; drug resistance; synergistic effect; drug interaction; enhanced permeation and retention”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Manuscript “Complex Sameness” From Akina, Inc.-FDA Research Highlights Q1/Q2 Assay Methodologies

Monday, March 18, 2019, 4:11 PM ET

In addition to providing polymer products through the PolySciTech product line, Akina, Inc. also provides analytical and research services through the Akinalytics division (http://www.akinalytics.com/). A recent publication relates the development work performed with the Food and Drug Administration to deconstruct microparticle formulations which are constructed of more than one type of PLGA (varying lactide ratio) by applying a series of semi-solvents which dissolve higher-lactide content PLGA sequentially so each fraction can be assayed. Trelstar ® 22.5 mg dose was deconstructed by this method and each fraction was assayed. This research holds promise to develop assays which enable determination of sameness between Reference-Listed Drug (RLD) and a proposed generic. Read more: Skidmore, Sarah, Justin Hadar, John Garner, Haesun Park, Kinam Park, Yan Wang, and Xiaohui Jiang. “Complex sameness: Separation of mixed poly (lactide-co-glycolide) s based on the lactide: glycolide ratio.” Journal of Controlled Release (2019). https://doi.org/10.1016/j.jconrel.2019.03.002 [Link for 50-Days of Free access (May 5, 2019): https://authors.elsevier.com/c/1YjxgcI2~p~xz]

“Abstract: Poly (lactide-co-glycolide) (PLGA) has been used for making injectable, long-acting depot formulations for the last three decades. An in depth understanding of PLGA polymers is critical for development of depot formulations as their properties control drug release kinetics. To date, about 20 PLGA-based formulations have been approved by the U.S. Food and Drug Administration (FDA) through new drug applications, and none of them have generic counterparts on the market yet. The lack of generic PLGA products is partly due to difficulties in reverse engineering. A generic injectable PLGA product is required to establish qualitative and quantitative (Q1/Q2) sameness of PLGA to that of a reference listed drug (RLD) to obtain an approval from the FDA. Conventional characterizations of PLGA used in a formulation rely on measuring the molecular weight by gel permeation chromatography (GPC) based on polystyrene molecular weight standards, and determining the lactide:glycolide (L: G) ratio by 1H NMR and the end-group by 13C NMR. These approaches, however, may not be suitable or sufficient, if a formulation has more than one type of PLGA, especially when they have similar molecular weights, but different L:G ratios. Accordingly, there is a need to develop new assay methods for separating PLGAs possessing different L:G ratios when used in a drug product and characterizing individual PLGAs. The current work identifies a series of semi-solvents which exhibit varying degrees of PLGA solubility depending on the L:G ratio of the polymer. A good solvent dissolves PLGAs with all L:G ratios ranging from 50:50 to 100:0. A semi-solvent dissolves PLGAs with only certain L:G ratios. Almost all semi-solvents identified in this study increase their PLGA solubility as the L:G ratio increases, i.e., the lactide content increases. This lacto-selectivity, favoring higher L:G ratios, has been applied for separating individual PLGAs in a given depot formulation, leading to analysis of each type of PLGA. This semi-solvent method allows a simple, practical bench-top separation of PLGAs of varying L:G ratios. This method enables isolation and identification of individual PLGAs from a complex mixture that is critical for the quality control of PLGA formulations, as well as reverse engineering for generic products to establish the Q1/Q2 sameness. Keywords: PLGA separation L:G ratio Trelstar Q1/Q2 sameness Long-acting depot”

PLGA-Rhodamine/PLGA from PolySciTech used in development of peptide-targeted nanoparticles to macrophages for cancer therapy

Monday, March 18, 2019, 11:46 AM ET

Cancer is not a homogenous mass of cells, rather it is a complex mixture of microenvironment and tissue. Several factors of the microenvironment act to promote the growth of the cancer tumor. One of these is the presence of tumor-associated macrophages (immune cells) which promote the growth of cancer cells by suppressing the local immune system as well as by other mechanisms. One target for cancer therapy is to prevent the mechanisms of these support cells thereby leaving cancer more vulnerable and reducing its growth and survival. Recently, researchers at Purdue University and Soochow University (China) used PLGA (AP031) and fluorescent PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitec.com) to develop peptide-bound nanoparticles with selective uptake towards these macrophages. The fluorescent PLGA enables tracking the location of the nanoparticles as a means to confirm uptake. This research holds promise for the development of powerful and selective therapies against cancer. Read more: Pang, Liang, Yihua Pei, Gozde Uzunalli, Hyesun Hyun, L. Tiffany Lyle, and Yoon Yeo. "Surface Modification of Polymeric Nanoparticles with M2pep Peptide for Drug Delivery to Tumor-Associated Macrophages." Pharmaceutical Research 36, no. 4 (2019): 65. https://link.springer.com/article/10.1007/s11095-019-2596-5

“Purpose: Tumor-associated macrophages (TAMs) with immune-suppressive M2-like phenotype constitute a significant part of tumor and support its growth, thus making an attractive therapeutic target for cancer therapy. To improve the delivery of drugs that control the survival and/or functions of TAMs, we developed nanoparticulate drug carriers with high affinity for TAMs. Methods: Poly(lactic-co-glycolic acid) nanoparticles were coated with M2pep, a peptide ligand selectively binding to M2-polarized macrophages, via a simple surface modification method based on tannic acid-iron complex. The interactions of M2pep-coated nanoparticles with macrophages of different phenotypes were tested in vitro and in vivo. PLX3397, an inhibitor of the colony stimulating factor-1 (CSF-1)/CSF-1 receptor (CSF-1R) pathway and macrophage survival, was delivered to B16F10 tumors via M2pep-modified PLGA nanoparticles. Results: In bone marrow-derived macrophages polarized to M2 phenotype, M2pep-coated nanoparticles showed greater cellular uptake than those without M2pep. Consistently, M2pep-coated nanoparticles showed relatively high localization of CD206+ macrophages in B16F10 tumors. PLX3397 encapsulated in M2pep-coated nanoparticles attenuated tumor growth better than the free drug counterpart. Conclusion: These results support that M2pep-coating can help nanoparticles to interact with M2-like TAMs and facilitate the delivery of drugs that control the tumor-supportive functions of TAMs. KEY WORDS: Drug delivery M2pep PLGA nanoparticles PLX3397 tumor-associated macrophages”

-Biotech, Pharma, Cancer, Research (BPCR) is a free, 1-day scientific networking conference hosted by Akina, Inc. on Aug 28, 2019. See more and register to attend at www.bpcrconference.com

Thermogelling PLGA-PEG-PLGA from PolySciTech used in research of healing/scar-formation of cardiovascular tissue

Friday, March 15, 2019, 1:44 PM ET

The formation of scar tissue, or fibrosis, is a common response to injury and is part of the healing process of most tissues. Superficial scarring is benign however when it occurs in critical areas (such as cardiovascular tissue post balloon angioplasty) it can be lethal. Recently, researchers at The Ohio State University and University of Wisconsin used thermogelling PLGA-PEG-PLGA (AK012) from PolySciTech (www.polyscitech.com) to deliver centrinone-B (a PLK4 inhibitor) as part of modeling the effect that blocking PLK4 had on healing and scar formation. This research holds promise to aid in developing therapeutics to improve cardiovascular healing as part of treatment of atherosclerosis and hypertension. Read more: Jing Li, Go Urabe, Mengxue Zhang, Yitao Huang, Bowen Wang, Lynn Marcho, Hongtao Shen, K. Craig Kent, Lian-Wang Guo “A non-canonical role of polo-like kinase-4 in adventitial fibroblast cell type transition” bioRxiv (2019) 570267; doi: https://doi.org/10.1101/570267

“Abstract: Fibroblast-to-myofibroblast transition (FMT) is central to fibrosis. A divergent member of the polo-like kinase family, PLK4 is known for its canonical role in centriole duplication. Whether this mitotic factor regulates cell type transitions was underexplored. Here we investigated PLK4’s activation and expression and regulations thereof in platelet-derived growth factor (PDGF)- induced FMT of rat aortic adventitial fibroblasts. PLK4 inhibition (with centrinone-B or siRNA) diminished not only PDGF AA-induced proliferation/migration, but also smooth muscle a-actin and its transcription factor serum response factor’s activity. While PDGFR inhibition abrogated AA-stimulated PLK4 activation (phosphorylation) and mRNA/protein expression, inhibition of p38 downstream of PDGFR had a similar effect. Further, the transcription of PLK4 (and PDGFRa) was blocked by pan-inhibition of the bromo/extraterminal-domains chromatin-bookmark readers (BRD2, BRD3, BRD4), an effect herein determined via siRNAs as mainly mediated by BRD4. In vivo, periadventitial administration of centrinone-B reduced collagen content and thickness of the adventitia in a rat model of carotid artery injury. Thus, we identified a non-canonical role for PLK4 in FMT and its regulation by a BRD4/PDGFRa-dominated pathway. This study implicates a potential PLK4-targeted antifibrotic intervention. Keywords: PLK4, PDGF receptor-a, BRD4, fibroblast-to-myofibroblast transition, fibrosis”

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These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.2847740650177 seconds)


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