Technical Blog
John GarnerJohn Garner, General Manager

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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PLGA from PolySciTech used in research on vaccine delivery

Wednesday, June 29, 2022, 2:00 PM ET

Vaccines can be leveraged as a life-saving technology against a wide variety of diseases. There are many mechanisms to provide vaccines and the mode of application drives efficacy. Recently, PLGA from PolySciTech (www.polyscitech.com) was utilized by researchers at Massachusetts Institute of Technology to to investigate microneedle delivery of vaccines. This research holds promise to improve disease prevention in the future. Read more: Sarmadi, Morteza. "Microscale polymeric-based technologies for controlled vaccine delivery." PhD diss., Massachusetts Institute of Technology, 2022. https://dspace.mit.edu/handle/1721.1/143281

“ABSTRACT: Outbreak of infectious diseases such as COIVD-19 is one of the most critical challenges threatening global health and economy, particularly in developing world. Technologies that can improve delivery, access, effectiveness, and stability of vaccination, as a promising tool against outbreaks, would be strategic tools to potentially save lives and avoid trillions of dollars in financial losses. Our group has been developing such platform technologies for controlled delivery and tracking of vaccines. This thesis investigates further development of these technologies toward clinical translation. In the first part, we investigate a locally injectable microparticle system with a core-shell microstructure made from a novel 3D printing process compatible with biodegradable polymers. These microparticles can be used for delayed, pulsatile release of vaccines, therefore reducing the number of administrations to a single one. We study two translational aspects of core-shell microparticles, namely, injectability, and mechanism of pulsatile release. To study injectability, we use a wide range of tools, namely, multiphysics simulation, experiments, machine learning, and 3D printing to establish a framework for optimal injection of microparticle-based drugs. To study the mechanism of pulsatile release, we integrate various experimental tools with multiphysics simulations to form a model describing the mechanism of degradation and pulsatile release from core-shell particles. In the next phase of this thesis we move forward to a transdermal dissolvable microneedle patch without the need for injections. These microneedle patches can be used to track medical record on patient without the need for expensive healthcare infrastructure--a challenge in developing world. Using extensive computational modeling, we establish a design framework for microneedle devices, widely applicable to any microneedle system. Best trade-off design is then selected for administrations in vivo. We further develop a machine learning algorithm coupled with image processing tools to provide long-term pattern classification capability for encoding information transferred by microneedles to the patient, in an automated and robust fashion. Results of this thesis could be of great interest to development of next generation biomedical devices for controlled vaccine delivery and other applications.”

PEG-PLGA and Mal-PEG-PLGA from PolySciTech used in research on Lupus.

Wednesday, June 29, 2022, 1:59 PM ET

Systemic lupus erythematosus (SLE) is the most common type of lupus. SLE is an autoimmune disease in which the immune system attacks its own tissues. Recently, researchers at Harvard University and Mitobridge, Inc. used mPEG-PLGA (5K-30K, cat# AK102) and PLGA-PEG-Mal (5K-30K, cat# AI110) from PolySciTech (www.polyscitech.com) to develop nanoparticles as part of investigating the pathogenicity of lupus. This research holds promise to provide further treatments for lupus. Read More: Chen, P.M., Katsuyama, E., Satyam, A., Li, H., Rubio, J., Jung, S., Andrzejewski, S., Becherer, J.D., Tsokos, M.G., Abdi, R. and Tsokos, G.C., 2022. CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. Science Advances, 8(24), p.eabo4271. https://www.science.org/doi/abs/10.1126/sciadv.abo4271

“Abstract: Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD+, is up-regulated in CD8+ T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8+ T cell–targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.”

PLGA-PEG from Akina used in research on tumor-mimicking hydrogels for in-vitro testing applications.

Wednesday, June 29, 2022, 1:44 PM ET

In order to develop anticancer medications assays must be developed which enable accurate determination of the efficacy of prototype medicines. Because cancer is a complex 3D structure within the human body these assays need to include the nuances present in the microenvironment. Recently, researchers at University of Queensland (Australia) used PEG-PLGA (Cat# AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles and use these as part of testing hydrogel-based mimics of tumors for in-vitro development. This research holds promise to improve cancer drug development processes in the future. Read more: Cameron, Anna P., Bijun Zeng, Yun Liu, Haofei Wang, Farhad Soheilmoghaddam, Justin Cooper-White, and Chun-Xia Zhao. "Biophysical properties of hydrogels for mimicking tumor extracellular matrix." Biomaterials Advances 136 (2022): 212782. https://www.sciencedirect.com/science/article/pii/S2772950822000590

“Highlights: Evaluation of biophysical attributes of Matrigel, collagen gel and agarose gel. Characterization of complex modulus, loss tangent, permeability and pore size of hydrogels. A new and facile method for the characterization of hydrogel microstructures. A microfluidic approach for measuring hydrogel permeability. Abstract: The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random. This study systematically evaluates the biophysical attributes of three widely used natural hydrogels (Matrigel, collagen gel and agarose gel) including complex modulus, loss tangent, diffusive permeability and pore size. A new and facile method was developed combining Critical Point Drying, Scanning Electron Microscopy imaging and a MATLAB image processing program (CSM method) for the characterization of hydrogel microstructures. This CSM method allows accurate measurement of the hydrogel pore size down to nanometer resolution. Furthermore, a microfluidic device was implemented to measure the hydrogel permeability (Pd) as a function of particle size and gel concentration. Among the three gels, collagen gel has the lowest complex modulus, medium pore size, and the highest loss tangent. Agarose gel exhibits the highest complex modulus, the lowest loss tangent and the smallest pore size. Collagen gel and Matrigel produced complex moduli close to that estimated for cancer ECM. The Pd of these hydrogels decreases significantly with the increase of particle size. By assessing different hydrogels' biophysical characteristics, this study provides valuable insights for tailoring their properties for various three-dimensional cancer models.”

Aquagel from PolySciTech used in development of inflatable underwater Naval sonar sensors

Wednesday, June 29, 2022, 1:43 PM ET

Compressive sensors enable sonar detection underwater with less hardware complexity. This allows for cheap, easily deployable, efficient, sonar detection systems that can be used for a wide array of applications. Recently, researchers at the Office of Naval Research Science & Technology utilized Aquagel from Akina, Inc. (https://akinainc.com/polyscitech/products/aquagel/index.php) to develop underwater deployable sonar sensing arrays. This research holds promise to improve detection capabilities for both civillian and military applications. Read more: Ouyang, Bing. Robust Co-Prime Sensing with Underwater Inflatable Passive Sonar Arrays. FLORIDA ATLANTIC UNIV FORT PIERCE FL, 2022. https://apps.dtic.mil/sti/pdfs/AD1169163.pdf

“ABSTRACT: This final technical report describes the effort from May 2018 to September 2021 to accomplish the project objective of Robust Co-Prime Sensing with Underwater Inflatable Passive Sonar Arrays. In many scientific and defense surveillance missions, reducing the sensing systems’ size, weight, and power (SWaP) is critical to accomplishing the intended objectives [1]. The long-term goal of this research is to develop energy-efficient and low-cost underwater inflatable structures that will be the building blocks in many naval applications. While compressive sensing (CS) has been adopted at the backend to maintain signal fidelity with fewer data and reduce the sensing hardware’s complexity, SWaP reduction can also be achieved with intelligent mechanical design. The inflatable structure is adopted for the mechanical design of this sonar array. The inflatable structure, also called the deployable structure, is a folded package with compact stowed dimensions. It can be detached from a carrying platform and morphs into its final form at the destination. On the algorithm side, the concept of the co-prime array is adopted. A co-prime array employs two interleaved uniform linear subarrays with several co-prime elements and inter-element spacing. It can resolve a much higher number of sources than a conventional uniform half-wavelength spaced array for a given number of sensors. Therefore, integrating these two concepts, i.e., “two-way compression,” reduces both the structural dimension of a sonar array and the number of hydrophones in the array. During the three-year funding period, the team investigated alternatives to the conventional Mechanical Based Expansion (MBE), including Physics-Based Expansion (PBE) and Chemical Based Expansion (CBE). The feasibility of these techniques, particularly the PBE approach, has been validated through numerical modeling, lab test, and field study. Our study has produced two pending patents, and one journal paper (in press). The results have also been presented at multiple technical conferences.”

PLGA-PEG-amine from PolySciTech used in development of Photodynamic therapy delivery system for targeted treatment of cancer

Wednesday, June 15, 2022, 2:07 PM ET

Photodynamic therapy is a process by which a delivery system is combined with external illumination as a means to specifically target and affect tumor cells. A specific challenge for this system is delivery of the appropriate photosensitizer molecule to the site of action. Recently, researchers at University of Madrid and Harvard Medical School used PLGA-PEG-NH2 (cat# AI058) from the PolySciTech (www.polyscitech.com) division of Akina, Inc to develop a delivery system. They reacted this with hyaluronic acid to create a unique nanoparticle for carrying of Ruthenium complexes. This research hold promise to improve therapy options against cancer in the future. Read more: Quilez Alburquerque, jose and Saad, Mohammad Ahsan and Descalzo, Ana B. and Orellana, Guillermo and Hasan, Tayyaba, Hyaluronic Acid-Poly(Lactic-Co-Glycolic Acid) Nanoparticles with a Ruthenium Photosensitizer Cargo for Photokilling of Oral Cancer Cells. Available at SSRN: https://ssrn.com/abstract=4131246or http://dx.doi.org/10.2139/ssrn.4131246

“Photodynamic therapy (PDT), a combination of light, molecular oxygen and a photosensitizing dye, has gained attention as a promising technique to treat various types of cancers. Among all the photosensitizers reported so far, ruthenium(II) polypyridyl complexes exhibit unique photophysical and photobiological features owing to their photostability, ms triplet excited states, and ability to undergo both ‘type I’ and ‘type II’ reactions in their photodynamic action. We report the synthesis a novel Ru(II) complex containing one 2,2'-biimidazole (bim) and two tetramethylphenanthroline (tmp) ligands that sensitizes the simultaneous production of superoxide anion (O 2 · - ) and singlet oxygen ( 1 O 2 ) upon irradiation with blue-green light. To improve its solubility and bioavailability, a zero-order degradation-controlled release formulation based on self-assembled hyaluronic acid (HA)–poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was prepared for its topical application in oral cancer cells (TR146 cell line). These NPs (152 nm diameter) showed 70% Ru-complex encapsulation efficiency, high physiological stability, low polydispersity index (0.12), and a sensitizer release enhanced by the hyaluronidase enzyme overexpressed in many cancer cells. Both the free complex and its nanocarrier are internalized by the TR146 cells, displaying >90% in vitro cytotoxicity under 470 nm activation (50 J cm⁻ 2 ), highlighting their potential as PDT agents. As hypoxia associated with oral and other cancers is a major barrier to photodynamic therapy which is being clinically employed for oral cancer management, the Ru(II) complex loaded nanocarrier developed in this study can be effective in the treatment of early stage oral cancers and disinfection of wounds where light penetration is not a pre-requisite. Keywords: Photodynamic therapy, Ru(II) complex, hyaluronic acid-poly(lactic-co-glycolic acid), superoxide anion”

PLGA-PEG-PLGA from PolySciTech used in delivery of Ponatinib for cancer therapy

Monday, June 6, 2022, 1:28 PM ET

Tyrosine kinase inhibitors (TKIs) are a new generation of anti-cancer drugs which can prevent cancer growth and spread however these do display cardiotoxicity. Encapsulating the TKI can prevent toxic effects towards heart tissue. Recently, researchers at Qatar University and Ss. Cyril and Methodius University in Skopje used PLGA-PEG-PLGA (cat# AK032) from PolySciTech (www.polyscitech.com) to make nanoparticles loaded with Ponatinib and these were used for measurement of toxicty and efficacy in a zebrafish model. This research holds promise to improve therapies against cancer in the future. Read more: Al-Thani, Hissa F., Samar Shurbaji, Zain Zaki Zakaria, Maram H. Hasan, Katerina Goracinova, Hesham M. Korashy, and Huseyin C. Yalcin. "Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model." Materials 15, no. 11 (2022): 3960. https://www.mdpi.com/1996-1944/15/11/3960

“Abstract: Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells’ proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg/mL are non-toxic/non-cardio-toxic in the studied zebrafish xenograft model. Keywords: zebrafish; leukemia; nanomedicine; nanoparticle; pre-clinical; cardiotoxicity; cancer; Ponatinib; xenograft; PLGA”

PLLA-Fluorescein from PolySciTech used in development of contraceptive microneedle

Thursday, May 26, 2022, 1:58 PM ET

One method for drug-delivery is to utilize microneedles, patches comprised of very small biodegradable needles too small to see. These can be used for long-lasting delivery of agents including contraceptives. Recently, researchers at Georgia Institute of Technology, University of Michigan, and Wuhan University (China) used PLLA-Fluorescein (AV004) from PolySciTech (www.polyscitech.com) to create fluorescently strained microparticles for delivery of contraceptive hormone, levonorgestrel. This research holds promise to provide for extended contraceptive action in a less invasive manner than existing products such as IUDs. Read more: Li, Wei, Jonathan Yuxuan Chen, Richard N. Terry, Jie Tang, Andrey Romanyuk, Steven P. Schwendeman, and Mark R. Prausnitz. "Core-shell microneedle patch for six-month controlled-release contraceptive delivery." Journal of Controlled Release 347 (2022): 489-499. https://www.sciencedirect.com/science/article/pii/S0168365922002656

“Highlights: Developed a novel core-shell microneedle where the shell is a rate-controlling membrane to achieve zero-order drug release. Constructed the core-shell structure by sequential casting into a single mold by solvent engineering. Achieved six-month controlled-release contraceptive delivery in vitro. Abstract: There is a tremendous need for simple-to-administer, long-acting contraception, which can increase access to improved family planning. Microneedle (MN) patches enable simple self-administration and have previously been formulated for 1–2 months-controlled release of contraceptive hormone using monolithic polymer/drug MN designs having first-order release kinetics. To achieve zero-order release, we developed a novel core-shell MN patch where the shell acts as a rate-controlling membrane to delay release of a contraceptive hormone, levonorgestrel (LNG), for 6 months. In this approach, LNG was encapsulated in a poly(lactide-co-glycolide) (PLGA) core surrounded by a poly(l-lactide) (PLLA) shell and a poly(D,L-lactide) (PLA) cap that were fabricated by sequential casting into a MN mold. Upon application to skin, the core-shell MNs utilized an effervescent interface to separate from the patch backing within 1 min. The core-shell design limited the initial 24 h burst release of LNG to 5.8 ± 0.5% and achieved roughly zero-order LNG release for 6.2 ± 0.1 months in vitro. A monolithic MN patch formulated with the same LNG and PLGA core, but without the rate-controlling PLLA shell and PLA cap had a larger LNG burst release of 22.6 ± 2.0% and achieved LNG release for just 2.1 ± 0.2 months. This study provides the first core-shell MN patch for controlled months-long drug release and supports the development of long-acting contraception using a simple-to-administer, twice-per-year MN patch.”

PLCL from PolySciTech used in development of sprayable tissue adhesive for surgical applications

Wednesday, May 18, 2022, 3:51 PM ET

After surgery it is not uncommon for various internal tissues to heal together inappropriately, i.e. certain layers of tissue will heal to one another rather than as discrete layers. This problem can lead to adhesions, fibrous bridges that connect tissue surfaces together and is usually affiliated with an inflammatory response post-surgery. These adhesions can lead to severe pain as well as bowel obstruction and infertility, depending on their location. Recently, researchers at University of Maryland, Massachusetts Institute of Technology, and Children’s National Medical Center utilized various PLCL polymers (cat# AP212, AP178, AP179, and AP151) from PolySciTech (www.polyscitech.com) to create a spray-on layer of biodegradable polymer that reduces the formation of these adhesions between tissues. This research holds promise to reduce this common post-surgical complication. Read more: Erdi, Metecan, Selim Rozyyev, Manogna Balabhadrapatruni, Michele S. Saruwatari, John L. Daristotle, Omar B. Ayyub, Anthony D. Sandler, and Peter Kofinas. "Sprayable Tissue Adhesive with Biodegradation Tuned for Prevention of Post‐Operative Abdominal Adhesions." Bioengineering & Translational Medicine: e10335. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10335

“Abstract: Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following post-operative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in-situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy to apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through design of PLCL blends comprised of highly adhesive “low” molecular weight (LMW) constituents in a mechanically robust “high” molecular weight (HMW) matrix. In-vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm treated controls.”

PLCL from PolySciTech used in development of burn wound healing scaffold of cells and polymer mesh.

Tuesday, May 3, 2022, 12:06 PM ET

Deep tissue burn wounds heal poorly on their own due to extensive cellular damage and lost flesh. Recently, researchers at Georgetown University, University of Maryland, Children’s National Medical Center, Massachusetts Institute of Technology, and MedStar Washington Hospital Center used PLCL (Cat# AP179) from PolySciTech (www.polyscitech.com) to create a blow-spun polymer formulation which can support a cell suspension. Applying this over a burn wound can aid in regrowth and repair of the damaged tissue. This research holds promise to assist in healing of traumatic burn wounds. (Screen-shot Video available here: https://ars.els-cdn.com/content/image/1-s2.0-S0305417922000122-mmc28.mp4) Read more: Carney, Bonnie C., Mary A. Oliver, Metecan Erdi, Liam D. Kirkpatrick, Stephen P. Tranchina, Selim Rozyyev, John W. Keyloun et al. "Evaluation of Healing Outcomes Combining A Novel Polymer Formulation with Autologous Skin Cell Suspension to Treat Deep Partial and Full Thickness Wounds in a Porcine Model; A Pilot Study." Burns (2022). https://www.sciencedirect.com/science/article/pii/S0305417922000122

“Highlights: Autologous skin cell suspensions sprayed onto wounds can be primarily dressed with a solution-blow spun polymer formulation. Polymer is not cytotoxic to cells and wound beds. Wound closure and scar levels are similar to controls, but usability and sealing of wounds is preferred in polymer-dressed wounds. Abstract: Autologous skin cell suspensions (ASCS) can treat burns of varying depths with the advantage of reduced donor site wound burden. The current standard primary dressing for ASCS is a nonabsorbant, non-adherent, perforated film (control) which has limited conformability over heterogeneous wound beds and allows for run-off of the ASCS. To address these concerns, a novel spray-on polymer formulation was tested as a potential primary dressing in porcine deep partial thickness (DPT) and full thickness (FT) wounds. It was hypothesized that the polymer would perform as well as control dressing when evaluating wound healing and scarring. DPT or FT wounds were treated with either a spray-on poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone) (PLCL) formulation or control ASCS dressings. Throughout the experimental time course (to day 50), we found no significant differences between polymer and control wounds in % re-epithelialization, graft-loss, epidermal or dermal thickness, or % dermal cellularity in either model. Pigmentation, erythema, elasticity, and trans-epidermal water loss (TEWL), were not significantly altered between the treatment groups, but differences between healing wounds/scars and un-injured skin were observed. No cytotoxic effect was observed in ASCS incubated with the PLGA and PLCL polymers. These data suggest that the novel spray-on polymer is a viable option as a primary dressing, with improved ease of application and conformation to irregular wounds. Polymer formulation and application technique should be a subject of future research.”

PLGA from PolySciTech used in development of microparticle-based treatment of osteoarthritis

Tuesday, May 3, 2022, 11:58 AM ET

Osteoarthritis is a degenerative disease affecting the cartilage in joints leading to significant damage, pain, and loss of functionality. Non-surgical treatment options are highly limited to symptomatic relief. Drug delivery to cartilage and bone tissues in a systemic sense is complicated by relatively poor blood flow in these area. Recently, researchers at Indian Institute of Science and MS Ramaiah Medical College (India) used PLGAs (cat# AP041, AP089, AP036) from PolySciTech (www.polyscitech.com) to create a series of microparticles to release rapamycin locally. This drug acted to prevent senescence and increase cartilage production. This research holds promise to improve therapies against arthritis. Read more: Dhanabalan, Kaamini M., Ameya A. Dravid, Smriti Agarwal, Ramanath K. Sharath, Ashok Kumar Padmanabhan, and Rachit Agarwal. "Intra‐articular Injection of Rapamycin Microparticles Prevent Senescence and Effectively Treat Osteoarthritis." Bioengineering & Translational Medicine: e10298. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10298

“Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Rapamycin-loaded in poly (lactic-co-glycolic acid) microparticles (RMPs) induced autophagy, prevented senescence, and sustained sulphated glycosaminoglycans(sGAG) production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, the study demonstrates the feasibility of using RMPs as a potential clinically translatable therapy to prevent the progression of post-traumatic osteoarthritis.”

PLGA from PolySciTech used in development of cardiovascular targeting nanoparticle for heart therapies

Tuesday, April 19, 2022, 2:45 PM ET

Notch, a specific signaling protein, is essential for proper development of the heart as this regulates signals between the endocardium and myocardium for chamber development. The ability to deliver genetic factors to correct issues with this signal formation can be used to aid in specific cardiovascular disease or formation issues. Recently, researchers at University of Texas at Arlington, University of North Texas, and University of California, Irvine used PLGA (cat# AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with Notch plasmid to test the delivery of this gene to cells. They also tested the particles for any prevelant environmental danger which, owing to the biocompatible and biodegradable nature of PLGA, were minimal. Read more: Messerschmidt, V., Uday Chintapula, Fabrizio Bonetesta, Samantha Laboy-Segarra, Amir Naderi, K. Nguyen, Hung Cao, Edward Mager, and Juhyun Lee. "In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions." Frontiers in physiology 13 (2022). https://europepmc.org/articles/pmc8906778/bin/data_sheet_1.pdf

“Abstract: In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid via poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an in vivo experiment. In addition, we demonstrated the target delivery to the endothelium, including the endocardial layer, which is challenging to manipulate gene expression for cardiac functions due to the beating heart and rapid blood pumping. For this study, we used a zebrafish animal model and exposed it to nanoparticles at varying concentrations to observe for specific malformations over time for toxic effects of PLGA nanoparticles as a delivery vehicle. Our nanoparticles caused significantly less malformations than the positive control, ZnO nanoparticles. Additionally, the NICD plasmid was successfully delivered by PLGA nanoparticles and significantly increased Notch signaling related genes. Furthermore, our image based deep-learning analysis approach evaluated that the antibody conjugated nanoparticles were successfully bound to the endocardium to overexpress Notch related genes and improve cardiac function such as ejection fraction, fractional shortening, and cardiac output. This research demonstrates that PLGA nanoparticle-mediated target delivery to upregulate Notch related genes which can be a potential therapeutic approach with minimum toxic effects. Keywords: PLGA nanoparticles, toxicity, non-viral transfection, zebrafish, gene delivery, Notch signaling”

PLGA and PEG-PLGA from PolySciTech used in development of CRISPR technique for gene editing in vascular system

Tuesday, April 19, 2022, 2:44 PM ET

The ability to deliver genetic material and make edits to existing cells holds great promise for treating a wide variety of diseases. Recently, researchers at the Lurie Hospital of Chicago and Northwestern University used PLGA (Cat# AP121) and PEG-PLGA (Cat# AK026) from PolySciTech (www.polyscitech.com) to create nanoparticles for delivery of plasmid DNA to vascular components. This research holds promise to improve treatment against cardiovascular diseases by modifying genes to correct disease states. Read more: Zhang, Xianming, Hua Jin, Xiaojia Huang, Birendra Chaurasiya, Daoyin Dong, Thomas P. Shanley, and You-Yang Zhao. "Robust genome editing in adult vascular endothelium by nanoparticle delivery of CRISPR-Cas9 plasmid DNA." Cell reports 38, no. 1 (2022): 110196. https://www.sciencedirect.com/science/article/pii/S2211124721017009

“Highlights: PPP i.v. exhibits excellent biodistribution without specific liver accumulation. PPP efficiently delivers plasmid DNA in vivo targeting vascular ECs. PPP delivery of CRISPR plasmid decreases 80% protein in cardiopulmonary vascular ECs. The system induces genome editing of two genes in ECs without limitation on plasmid size. Abstract: Vascular endothelium plays a crucial role in vascular homeostasis and tissue fluid balance. To target endothelium for robust genome editing, we developed poly(ethylene glycol) methyl ether-block-poly(lactide-co-glycolide) (PEG-b-PLGA) copolymer-based nanoparticle formulated with polyethyleneimine. A single i.v. administration of mixture of nanoparticles and plasmid DNA expressing Cas9 controlled by CDH5 promoter and guide RNA (U6 promoter) induced highly efficient genome editing in endothelial cells (ECs) of the vasculatures, including lung, heart, aorta, and peripheral vessels in adult mice. Western blotting and immunofluorescent staining demonstrated an ∼80% decrease of protein expression selectively in ECs, resulting in a phenotype similar to that of genetic knockout mice. Nanoparticle delivery of plasmid DNA could induce genome editing of two genes or genome editing and transgene expression in ECs simultaneously. Thus, nanoparticle delivery of plasmid DNA is a powerful tool to rapidly and efficiently alter expression of gene(s) in ECs for cardiovascular research and potential gene therapy. Keywords: CRISPR-Cas9 cardiovascular disease endothelial cell genome editing nanoparticle non-viral CRISPR delivery gene delivery gene therapy endothelium targeting lung diseases”

PLA-PEG from PolySciTech used in development of bronchial-targetting particles for cystic fibrosis therapy

Tuesday, April 12, 2022, 1:47 PM ET

Cystic fibrosis is the second most common lethal inherited disorder related to a specific mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The potential for gene-editing may provide a treatment for this incurable disase. Recently, researchers at Yale University used PEG-PLA (cat# AK054) from PolySciTech (www.polyscitech.com) to test the effect of nanoparticle decorations on bronchial uptake from an inhaled formulation. This research holds promise to improve treatments against cystic fibrosis in the future. Read more: Luks, Valerie L., Hanna Mandl, Jenna DiRito, Christina Barone, Mollie R. Freedman-Weiss, Adele S. Ricciardi, Gregory G. Tietjen, Marie E. Egan, W. Mark Saltzman, and David H. Stitelman. "Surface conjugation of antibodies improves nanoparticle uptake in bronchial epithelial cells." PloS one 17, no. 4 (2022): e0266218. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266218

“Abstract: Background: Advances in Molecular Therapy have made gene editing through systemic or topical administration of reagents a feasible strategy to treat genetic diseases in a rational manner. Encapsulation of therapeutic agents in nanoparticles can improve intracellular delivery of therapeutic agents, provided that the nanoparticles are efficiently taken up within the target cells. In prior work we had established proof-of-principle that nanoparticles carrying gene editing reagents can mediate site-specific gene editing in fetal and adult animals in vivo that results in functional disease improvement in rodent models of β-thalassemia and cystic fibrosis. Modification of the surface of nanoparticles to include targeting molecules (e.g. antibodies) holds the promise of improving cellular uptake and specific cellular binding. Methods and findings: To improve particle uptake for diseases of the airway, like cystic fibrosis, our group tested the impact of nanoparticle surface modification with cell surface marker antibodies on uptake in human bronchial epithelial cells in vitro. Binding kinetics of antibodies (Podoplanin, Muc 1, Surfactant Protein C, and Intracellular Adhesion Molecule-1 (ICAM)) were determined to select appropriate antibodies for cellular targeting. The best target-specific antibody among those screened was ICAM antibody. Surface conjugation of nanoparticles with antibodies against ICAM improved cellular uptake in bronchial epithelial cells up to 24-fold. Conclusions: This is a first demonstration of improved nanoparticle uptake in epithelial cells using conjugation of target specific antibodies. Improved binding, uptake or specificity of particles delivered systemically or to the luminal surface of the airway would potentially improve efficacy, reduce the necessary dose and thus safety of administered therapeutic agents. Incremental improvement in the efficacy and safety of particle-based therapeutic strategies may allow genetic diseases such as cystic fibrosis to be cured on a fundamental genetic level before birth or shortly after birth.”

Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of doxorubicin delivery system to prevent posterior capsule opacification

Tuesday, April 12, 2022, 1:46 PM ET

After surgical repairs made to the eye including cornea transplant or cataracts removal there are instances in which scar tissue grows along the ocular lense components leading to cloudiness or haze which reduces vision in the patient. Recently, researchers at Rowan University used thermogelling PLGA-PEG-PLGA (cat# AK097) from PolySciTech (www.polyscitech.com) to create a gel for controlled delivery of nucleic-acid nanocarriers of doxorubicin to prevent posterior capsule opacification (PCO). This research may assist in preserving sight after surgical repair. Read more: Osorno, Laura L., Robert J. Mosley, Patricia L. Poley, Jessica Bowers, Grzegorz Gorski, Jacquelyn Gerhart, Robert Getts, Mindy George-Weinstein, and Mark E. Byrne. "Sustained Release of Antibody-Conjugated DNA Nanocarriers from a Novel Injectable Hydrogel for Targeted Cell Depletion to Treat Cataract Posterior Capsule Opacification." Journal of Ocular Pharmacology and Therapeutics (2022). https://www.liebertpub.com/doi/abs/10.1089/jop.2021.0111

“Abstract: Purpose: To compare a novel, sustained release formulation and a bolus injection of a targeted nanocarrier for the ability to specifically deplete cells responsible for the development of posterior capsule opacification (PCO) in week-long, dynamic cell cultures. Methods: A novel, injectable, thermosensitive poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer hydrogel was engineered for the sustained release of targeted, nucleic acid nanocarriers loaded with cytotoxic doxorubicin (G8:3DNA:Dox). Human rhabdomyosarcoma (RD) cells were used due to their expression of brain-specific angiogenesis inhibitor 1 (BAI1), a specific marker for the myofibroblasts responsible for PCO. Under constant media flow, nanocarriers were injected into cell cultures as either a bolus or within the hydrogel. Cells were fixed and stained every other day for 7 days to compare targeted depletion of BAI1+ cells. Results: The formulation transitions to a gel at physiological temperatures, is optically clear, noncytotoxic, and can release G8:3DNA:Dox nanocarriers for up to 4 weeks. In RD cell cultures, G8:3DNA:Dox nanocarriers specifically eliminated BAI1+ cells. The bolus nanocarrier dose showed significantly reduced cell depletion overtime, while the sustained release of nanocarriers showed increased cell depletion over time. By day 7, <2% of BAI1+ cells were depleted by the bolus injection and 74.2% BAI1+ cells were targeted by the sustained release of nanocarriers. Conclusions: The sustained release of nanocarriers from the hydrogel allows for improved therapeutic delivery in a dynamic system. This method can offer a more effective and efficient method of prophylactically treating PCO after cataract surgery.”

PLGA from PolySciTech used in development of BMP-2 loaded particles for bone tissue engineering.

Tuesday, April 12, 2022, 1:45 PM ET

There are many situations in which bone can be damaged or lost including severe trauma (e.g. car accidents) or diseases such as cancer which necessitate removal of diseased portions. As bone tissue does not naturally regenerate damage which exceeds a certain volume or distance (i.e. a critical sized defect, bone can heal ‘breaks’ between adjacent pieces, but not large holes or amputations) this damage can leave patients with permanent, debilitating injuries. Recently, Gwangju Institute of Science and Technology and Korea Institute of Machinery and Materials (Korea) used PLGA (cat# AP018, AP036) from PolySciTech (www.polyscitech.com) to generate BMP-2 (a protein which induces bone healing) loaded particles and utilized these in a cell-scaffold to provide a structure to enable bone healing. This research holds promise to improve reconstructive surgery for repair of damage to bone tissue caused by trauma or surgery. Read more: Choe, Goeun, Mingyu Lee, Seulgi Oh, Ji Min Seok, Junghyun Kim, Seunghyun Im, Su A. Park, and Jae Young Lee. "Three-dimensional bioprinting of mesenchymal stem cells using an osteoinductive bioink containing alginate and BMP-2-loaded PLGA nanoparticles for bone tissue engineering." Biomaterials Advances (2022): 212789. https://www.sciencedirect.com/science/article/pii/S2772950822000668

“Highlights: We produced bioinks using alginate and poly(lactic-co-glycolic acid) nanoparticles. Composite bioink showed enhanced printability and yielded stable printed constructs. Bone morphogenetic protein-2-loaded nanoparticles achieved 2-week sustained release. The novel bioink significantly promoted osteogenesis of mesenchymal stem cells. Abstract: Hydrogels mimicking the physicochemical properties of the native extracellular matrix have attracted great attention as bioinks for three-dimensional (3D) bioprinting in tissue engineering applications. Alginate is a widely used bioink with beneficial properties of fast gelation and biocompatibility; however, bioprinting using alginate-based bioinks has several limitations, such as poor printability, structural instability, and limited biological activities. To address these issues, we formulated various bioinks using bone morphogenetic protein-2 (BMP-2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and alginate for mesenchymal stem cell (MSC) printing and induction of osteogenic differentiation. Incorporation of PLGA nanoparticles into alginate could enhance the mechanical properties and printability of the bioink. In particular, Alg/NPN30 (30 mg/mL PLGA nanoparticles and 3% w/v alginate) was most suitable for 3D printing with respect to printability and stability. BMP-2-loaded PLGA nanoparticles (NPBMP-2) displayed sustained in vitro release of BMP-2 for up to two weeks. Further in vitro studies indicated that bioinks composed of alginate and NPBMP-2 significantly induced osteogenesis of the MSCs compared with other controls, evidenced by enhanced calcium deposition, alkaline phosphatase activity, and gene expression of osteogenic markers. Our novel bioink consisting of widely used biocompatible components displays good printability, stability, and osteogenic inductivity, and holds strong potential for cell printing and bone tissue engineering applications. Graphical abstract: Our novel bioink, consisting of alginate and bone morphogenetic protein-2 (BMP-2)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles, displays good printability, stability, and persistent osteogenic inductivity and will be beneficial for three-dimensional cell printing and bone tissue engineering applications.”

NIPAM based polymer from PolySciTech used in development of thermogel inkjet-printing technique

Monday, April 4, 2022, 1:08 PM ET

Advances in hydrogel and printing technology have enabled soft-printing techniques in which 3D structures are generated rapidly in desired format. Recently, researchers at Purdue University and Korea Institute of Industrial Technology used poly(n-isopropylacrylamide-co-acrylamide) (NIPAM-AM, cat# AO023) from PolySciTech (www.polyscitech.com) to investigate printing techniques and processes involved with print formation. This research holds promise to improve soft-printing techniques for a wide array of applications. Read more: Cheng, Cih, Yoon Jae Moon, Jun Young Hwang, George T-C. Chiu, and Bumsoo Han. "A scaling law of particle transport in inkjet-printed particle-laden polymeric drops." International Journal of Heat and Mass Transfer 191 (2022): 122840. https://www.sciencedirect.com/science/article/pii/S0017931022003222

“Highlights: A scaling law is proposed to predictively design inkjet printing processes of particle-laden hydrogels. A dimensionless similarity parameter is formulated and validated to predict particle distribution patterns in inkjet-printed hydrogel. Transport of particles in inkjet-printed hydrogels is determined by the balance of interstitial water flow and hindrance by the polymer matrix. Abstract: Hydrogels with embedded functional particulates are widely used to create soft materials with innovative functionalities. In order to advance these soft materials to functional devices and machines, critical technical challenges are the precise positioning of particulates within the hydrogels and the construction of the hydrogels into a complex geometry. Inkjet printing is a promising method for addressing these challenges and ultimately achieving hydrogels with voxelized functionalities, so-called digital hydrogels. However, the development of the inkjet printing process primarily relies on empirical optimization of its printing and curing protocol. In this study, a general scaling law is proposed to predict the transport of particulates within the hydrogel during inkjet printing. This scaling law is based on a hypothesis that water-matrix interaction during the curing of inkjet-printed particle-laden polymeric drops determines the intra-drop particle distribution. Based on the hypothesis, a dimensionless similarity parameter of the water-matrix interaction is proposed, determined by the hydrogel's water evaporation coefficient, particle size, and mechanical properties. The hypothesis was tested by correlating the intra-drop particle distribution to the similarity parameter. The results confirmed the scaling law capable of guiding ink formulation and printing and curing protocol. Keywords: Similarity Poroelasticity Thermally responsive polymer Particle distribution Digital hydrogel”

PEG-PLGA from PolySciTech used in evaluation of cancer in-vitro models.

Monday, April 4, 2022, 1:07 PM ET

To evaluate cancer therapies a realistic model must be utilized to determine the efficacy of the therapy preferably in-vitro or in animal model to prevent failed therapies from proceeding to clinical trials. Researchers at The University of Queensland used mPEG-PLGA (cat# AK026) from PolySciTech (www.polyscitech.com) to create nanoparticles to test a variety of biomimicking gels used as models for cancer behavior in-vitro. This research holds promise to improve testing methods for cancer therapies in the future. Read more: Cameron, Anna P., Bijun Zeng, Yun Liu, Haofei Wang, Mohammad Soheilmoghaddam, Justin Cooper-White, and Chun-Xia Zhao. "Biophysical properties of hydrogels for mimicking tumor extracellular matrix." Biomaterials Advances (2022): 212782. https://www.sciencedirect.com/science/article/pii/S2772950822000590

“Highlights: Evaluation of biophysical attributes of Matrigel, collagen gel and agarose gel. Characterization of complex modulus, loss tangent, permeability and pore size of hydrogels. A new and facile method for the characterization of hydrogel microstructures. A microfluidic approach for measuring hydrogel permeability. Abstract: The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random. This study systematically evaluates the biophysical attributes of three widely used natural hydrogels (Matrigel, collagen gel and agarose gel) including complex modulus, loss tangent, diffusive permeability and pore size. A new and facile method was developed combining Critical Point Drying, Scanning Electron Microscopy imaging and a MATLAB image processing program (CSM method) for the characterization of hydrogel microstructures. This CSM method allows accurate measurement of the hydrogel pore size down to nanometer resolution. Furthermore, a microfluidic device was implemented to measure the hydrogel permeability (Pd) as a function of particle size and gel concentration. Among the three gels, collagen gel has the lowest complex modulus, medium pore size, and the highest loss tangent. Agarose gel exhibits the highest complex modulus, the lowest loss tangent and the smallest pore size. Collagen gel and Matrigel produced complex moduli close to that estimated for cancer ECM. The Pd of these hydrogels decreases significantly with the increase of particle size. By assessing different hydrogels' biophysical characteristics, this study provides valuable insights for tailoring their properties for various three-dimensional cancer models. Keywords: Cancer Hydrogel Extracellular matrix Biophysical properties Complex modulus Loss tangent”

PEG-PLGA and PLGA from PolySciTech used in development of advanced cancer characterization techniques

Tuesday, March 29, 2022, 1:14 PM ET

Optimal use of ligands for active nanoparticle targeting requires selecting the correct antibody to attach to the specific target cell receptor. Recently, researchers at Barcelona Institute of Science and Technology (Spain) and Eindhoven University of Technology, (Netherlands) used PLGA (Cat# AP082) and PLGA-PEG-COOH (Cat# AI078) from PolySciTech (www.polyscitech.com) as part of their research into a quantitative imaging method whereby the optimal ligand is determined prior to nanoparticle preparation by use of direct stochastic optical reconstruction microscopy. This process was used to apply a systematic and intelligent design to selection of ligands for nanoparticle targeting. This research holds promise to improve therapies against cancer in the future. Read more: Woythe, Laura, Pranav Madhikar, Natalia Feiner-Gracia, Cornelis Storm, and Lorenzo Albertazzi. "A Single-Molecule View at Nanoparticle Targeting Selectivity: Correlating Ligand Functionality and Cell Receptor Density." ACS nano (2022). https://pubs.acs.org/doi/full/10.1021/acsnano.1c08277

“Antibody-functionalized nanoparticles (NPs) are commonly used to increase the targeting selectivity toward cells of interest. At a molecular level, the number of functional antibodies on the NP surface and the density of receptors on the target cell determine the targeting interaction. To rationally develop selective NPs, the single-molecule quantitation of both parameters is highly desirable. However, techniques able to count molecules with a nanometric resolution are scarce. Here, we developed a labeling approach to quantify the number of functional cetuximabs conjugated to NPs and the expression of epidermal growth factor receptors (EGFRs) in breast cancer cells using direct stochastic optical reconstruction microscopy (dSTORM). The single-molecule resolution of dSTORM allows quantifying molecules at the nanoscale, giving a detailed insight into the distributions of individual NP ligands and cell receptors. Additionally, we predicted the fraction of accessible antibody-conjugated NPs using a geometrical model, showing that the total number exceeds the accessible number of antibodies. Finally, we correlated the NP functionality, cell receptor density, and NP uptake to identify the highest cell uptake selectivity regimes. We conclude that single-molecule functionality mapping using dSTORM provides a molecular understanding of NP targeting, aiding the rational design of selective nanomedicines.”

PLGA-PEG-COOH from PolySciTech used in development of macrophage targeting nanoparticles for treatment of inflammation

Wednesday, March 23, 2022, 2:45 PM ET

The human immune system is a complex cascade of pathways, cells, and organs which exhibits several different modes of operation. The ability to modulate or adapt the action of this system can be used for both treatment of excess inflammation (i.e. rheumatoid arthritis and other autoimmune disorders) as well as to optimize vaccine action. Recently, researchers at University of Antwerp (Belgium) used PLGA-PEG-COOH (cat# AI171) from PolySciTech (www.polyscitech.com) to create macrophage targeting nanoparticles and tracked their behavior. This research holds promise to improve therapeutic options for treatment of many different diseases. Read more: Van Hees, Sofie, Kimberley Elbrink, Marjorie De Schryver, Peter Delputte, and Filip Kiekens. "Targeting of sialoadhesin-expressing macrophages through antibody-conjugated (polyethylene glycol) poly (lactic-co-glycolic acid) nanoparticles." Journal of Nanoparticle Research 24, no. 3 (2022): 1-13. https://link.springer.com/article/10.1007/s11051-022-05451-1

“This research aims to evaluate different-sized nanoparticles consisting of (polyethylene glycol) (PEG) poly(lactic-co-glycolic acid) (PLGA), loaded with fluorescein isothiocyanate for nanoparticle uptake and intracellular fate in sialoadhesin-expressing macrophages, while being functionalized with anti-sialoadhesin antibody. Sialoadhesin is a macrophage-restricted receptor, expressed on certain populations of resident tissue macrophages, yet is also upregulated in some inflammatory conditions. The nanocarriers were characterized for nanoparticle size (84–319 nm), zeta potential, encapsulation efficiency, and in vitro dye release. Small (86 nm) antibody-functionalized PEG PLGA nanoparticles showed persisting benefit from sialoadhesin-targeting after 24 h compared to the control groups. For small (105 nm) PLGA nanoparticles, uptake rate was higher for antibody-conjugated nanoparticles, though the total amount of uptake was not enhanced after 24 h. For both plain and functionalized small-sized (PEG) PLGA nanoparticles, no co-localization between nanoparticles and (early/late) endosomes nor lysosomes could be observed after 1-, 4-, or 24-h incubation time. In conclusion, decorating (PEG) PLGA nanocarriers with anti-sialoadhesin antibodies positively impacts macrophage targeting, though it was found to be formulation-specific.”

PLGA-PEG-PLGA from PolySciTech used in development of Rapamycin delivery system

Thursday, March 17, 2022, 2:48 PM ET

Rapamycin is a macrolide exhibiting potent antitumor and immunosuppressive activity. Unfortunately it has quick clearance and lacks targeted delivery for many applications. Recently, researchers used PLGA-PEG-PLGA (AK016) from PolySciTech (www.polyscitech.com) to create rapamycin-loaded nanoparticles inside of microspheres. Researchers tested the application of this delivery system towards the treatment of hemangiomas. This research holds promise to provide for improved application of rapamycin against a variety of disease states. Read more: Li, Haitao, Xin Wang, Xiaonan Guo, Qingkun Wan, Yunfei Teng, and Jianyong Liu. "Development of rapamycin-encapsulated exosome-mimetic nanoparticles-in-PLGA microspheres for treatment of hemangiomas." Biomedicine & Pharmacotherapy 148 (2022): 112737. https://www.sciencedirect.com/science/article/pii/S0753332222001251

“Highlights: Rapamycin-encapsulated exosome-mimetic nanoparticles-in-PLGA microspheres (RNM) show slow-release of rapamycin. RNM achieved superior therapeutic efficacy against hemangiomas over rapamycin. The therapeutic efficacy of RNM was attributed to its sustained release and suppression efficacy against HemSCs. Abstract: We have previously developed several kinds of rapamycin-encapsulated nanoparticles to achieve sustained release of rapamycin to treat hemangioma. However, lack of intrinsic targeting and easy clearance by the immune system are major hurdles that artificial fabricated nanoparticles must overcome. We constructed rapamycin-encapsulated macrophage-derived exosomes mimic nanoparticles-in-microspheres (RNM), to achieve the goal of continuous targeted therapy of hemangiomas. The rapamycin-encapsulated exosome mimic nanoparticles (RN) were firstly prepared by the extrusion-based method from the U937 cells (the human macrophage cell line). After then, RN was encapsulated with PLGA (poly(lactic-co-glycolic acid)) microspheres to obtain RNM. The release profile, targeting activity, and biological activity of RN and RNM were investigated on hemangioma stem cells (HemSCs). RN has a size of 100 nm in diameter, with a rapamycin encapsulation efficacy (EE) of 83%. The prepared microspheres RNM have a particle size of ~30 µm), and the drug EE of RNM is 34%. The sustained release of RNM can remarkably be achieved for 40 days. As expected, RN and RNM showed effective inhibition of cellular proliferation, significant cellular apoptosis, and remarkable repressed expression of angiogenesis factors in HemSCs. Our results showed that RNM is an effective approach for prolonged and effective delivery of rapamycin to hemangiomas.”

PLCL from PolySciTech used in development of tissue engineering for repair of torn rotator cuff and other injuries

Thursday, March 17, 2022, 2:47 PM ET

Depending on the nature and location of an injury healing may be difficult if not impossible as some tissues have either slow regeneration rate or do not heal at all unless certain conditions are met. An example of this is torn rotator cuff, a common shoulder injury, where the damaged tendons do not heal on their own. Recently, researchers at Novartis, Columbia University, University of Pennsylvania, and University of Connecticut used Poly(lactide-co-caprolactone) PLCL from PolySciTech (www.polyscitech.com) as part of their development of tissue engineering repairs for cartiladge and ligaments. This researchs holds promise to improve traumatic wound repair in the future. Read more: Prabhath, A., Vernekar, V.N., Esdaille, C.J., Eisenberg, E., Lebaschi, A., Badon, M., Seyedsalehi, A., Dzidotor, G., Tang, X., Dyment, N. and Thomopoulos, S., 2022. Pegylated insulin‐like growth factor‐1 biotherapeutic delivery promotes rotator cuff regeneration in a rat model. Journal of Biomedical Materials Research Part A. https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.37378

“Tears in the rotator cuff are challenging to repair because of the complex, hypocellular, hypovascular, and movement-active nature of the tendon and its enthesis. Insulin-like Growth Factor-1 (IGF-1) is a promising therapeutic for this repair. However, its unstable nature, short half-life, and ability to disrupt homeostasis has limited its clinical translation. Pegylation has been shown to improve the stability and sustain IGF-1 levels in the systemic circulation without disrupting homeostasis. To provide localized delivery of IGF-1 in the repaired tendons, we encapsulated pegylated IGF-1 mimic and its controls (unpegylated IGF-1 mimic and recombinant human IGF-1) in polycaprolactone-based matrices and evaluated them in a pre-clinical rodent model of rotator cuff repair. Pegylated-IGF-1 mimic delivery reestablished the characteristic tendon-to-bone enthesis structure and improved tendon tensile properties within 8 weeks of repair compared to controls, signifying the importance of pegylation in this complex tissue regeneration. These results demonstrate a simple and scalable biologic delivery technology alternative to tissue-derived grafts for soft tissue repair.”

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Wednesday, March 9, 2022, 3:37 PM ET

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PLA and PEG-PLA from PolySciTech used in the development of PLA-graft-insulin as a drug-delivery platform

Tuesday, March 8, 2022, 1:47 PM ET

Although polyethylene glycol (PEG) is generally considered to have a good safety profile, it does present an allergic reaction in certain patients. Alternative hydrophilic blocks can enable the generation of nanoparticles/micelles without using this compound. Recently, researchers at University of Salerno (Italy) used PLA (Cat# AP005 and Cat# AP231) and mPEG-PLA (Cat# AK009) from PolySciTech (www.polyscitech.com) to graft PLA polymers onto insulin and create nanoparticles loaded with this grafted PLA-Insulin material. This research holds promise to improve therapies against cancer and other diseases which bypass the issues that affect PEG. Read more: Sardo, Carla, Teresa Mencherini, Carmela Tommasino, Tiziana Esposito, Paola Russo, Pasquale Del Gaudio, and Rita Patrizia Aquino. "Inulin-g-poly-D, L-lactide, a sustainable amphiphilic copolymer for nano-therapeutics." Drug Delivery and Translational Research (2022): 1-17. https://link.springer.com/article/10.1007/s13346-022-01135-4

“Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV–Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.

PLGA from PolySciTech used in development of wound-healing antibiotic delivery system

Monday, February 28, 2022, 11:25 AM ET

Wounds often heal poorly due to bacterial intrusion. Recently, researchers at Assiut University (Egypt) utilized PLGA from PolySciTech (www.polyscitech.com) to create silk-PLGA nanoparticles to improve wound healing. This research holds promise to improve treatments against infected wounds. Read more: Abd El-Aziz, Fatma El-Zahraa A., Helal F. Hetta, Basma N. Abdelhamid, and Noura H. Abd Ellah. "Antibacterial and wound-healing potential of PLGA/spidroin nanoparticles: a study on earthworms as a human skin model." Nanomedicine 0 (2022). https://www.futuremedicine.com/doi/abs/10.2217/nnm-2021-0325

“Aim: The essential protein element of spider silk ‘spidroin’ was used to assess its impact on the wound-healing process. Methods: Spidroin nanoparticles (NPs) were prepared using poly(lactic-co-glycolic acid) polymer (PLGA/spidroin NPs) at different weight ratios (5:1, 10:1, 15:1) and were in vitro characterized. The optimized NPs were tested in vitro for release and antibacterial activity. To assess wound-healing effects, NPs were topically applied on surgically induced injuries in Allolobophora caliginosa earthworms as a robust human skin model. Results: Optimized NPs (173 ± 3 nm) revealed considerable antibacterial effect against Staphylococcus aureus and Escherichia coli. After 4 days of NPs application on wounds, macroscopical and histological examinations revealed a significant reduction in wound and re-epithelialization times. Conclusion: PLGA/spidroin NPs may represent a promising option for wound repair.”

PLGA from PolySciTech used in development of doxorubicin-loaded particles for chemoimmunotherapy applications

Monday, February 28, 2022, 11:24 AM ET

Immunogenic cell death (ICD) is an immune response against cancers which can be leveraged to eliminate tumors. Recently, researchers at Korea University and Korea Institute of Science and Technology utilized PLGA (cat# AP081) from PolySciTech (www.polyscitech.com) to create doxorubicin loaded nanoparticles for inducing ICD. This research holds promise to improve therapies against cancer in the future. Read more: Kim, Jeongrae, Yongwhan Choi, Suah Yang, Jaewan Lee, Jiwoong Choi, Yujeong Moon, Jinseong Kim et al. "Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses." Pharmaceutics 14, no. 3 (2022): 474. https://www.mdpi.com/1511014

“Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 ◦C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.19120311737061 seconds)


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