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 development of nanoparticles for oral delivery of peptides

Tuesday, January 25, 2022, 1:47 PM ET

Conventionally biologic drugs (peptide/protein based pharmaceuticals) can not be administered in an oral dose as a tablet or other form due to the stomach action which destroys (by natural design) proteins which enter it by digestive action. Furthermore, uptake across the intestinal lining is poor for these compounds reducing their oral bioavailability. Recently, researchers at Yantai University (China) used PLGA (AP040) from PolySciTech (www.polyscitech.com) to create modified nanoparticles to improve oral bioavailability of peptide drugs. This research holds promise to improve the development of novel modes of administration of peptide type drugs. Read more: Liang, Yanzi, Ruihuan Ding, Huihui Wang, Lanze Liu, Jibiao He, Yuping Tao, Zhenyu Zhao et al. "Orally administered intelligent self-ablating nanoparticles: a new approach to improve drug cellular uptake and intestinal absorption." Drug Delivery 29, no. 1 (2022): 305-315. https://www.tandfonline.com/doi/abs/10.1080/10717544.2021.2023704

“Oral drug delivery to treat diabetes is being increasingly researched. The mucus and the epithelial cell layers hinder drug delivery. We designed a self-ablating nanoparticle to achieve smart oral delivery to overcome the gastrointestinal barrier. We used the zwitterionic dilauroyl phosphatidylcholine, which exhibits a high affinity toward Oligopeptide transporter 1, to modify poly(lactic-co-glycolic acid) nanoparticles and load hemagglutinin-2 peptide to facilitate its escape from lysosomes. Nanoparticles exhibit a core–shell structure, the lipid layer is degraded by the lysosomes when the nanoparticles are captured by lysosomes, then the inner core of the nanoparticles gets exposed. The results revealed that the self-ablating nanoparticles exhibited higher encapsulation ability than the self-assembled nanoparticles (77% vs 64%) and with better stability. Quantitative cellular uptake, cellular uptake mechanisms, and trans-monolayer cellular were studied, and the results revealed that the cellular uptake achieved using the self-ablating nanoparticles was higher than self-assembling nanoparticles, and the number of uptake pathways via which the self-ablating nanoparticles functioned were higher than the self-assembling nanoparticles. Intestinal mucus permeation, in vivo intestinal circulation, was studied, and the results revealed that the small self-assembling nanoparticles exhibit a good extent of intestinal uptake in the presence of mucus. In vitro flip-flop, intestinal circulation revealed that the uptake of the self-ablating nanoparticles was 1.20 times higher than the self-assembled nanoparticles. Pharmacokinetic study and the pharmacodynamic study showed that the bioavailability and hypoglycemic effect of self-ablating nanoparticles were better than self-assembled nanoparticles.”

PLGA-rhodamine from PolySciTech used in research on dexamethasone nanoparticle-based delivery

Tuesday, January 18, 2022, 1:55 PM ET

Dexamethasone is an important anti-inflammatory compound used to treat arthritis. However its delivery and localization to the joint site remains poor. Recently, researchers at Université Paris-Saclay (France) and Universidade de Vigo (Spain) used PLGA-rhodamine (AV011) from PolySciTech (www.polyscitech.com) to create fluorescently traceable nanoparticles. This research holds promise to improve arthritis therapies in the future. Read more: Simón-Vázquez, Rosana, Nicolas Tsapis, Mathilde Lorscheider, Ainhoa Rodríguez, Patricia Calleja, Ludivine Mousnier, Encarnación de Miguel Villegas, África González-Fernández, and Elias Fattal. "Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles." Drug delivery and translational research (2022): 1-15. https://link.springer.com/article/10.1007/s13346-021-01112-3

“Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150 nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18 h, much longer than the commercial soluble drug dexamethasone phosphate (DSP). Biodistribution studies showed lower DXM concentrations in the liver, kidneys, and lungs when DXP-NPs were administered as compared with the soluble drug. Histology analysis revealed an improvement in the knee structure and reduction of cell infiltration in animals treated with the encapsulated DXP compared with the soluble DSP or non-treated animals. In summary, the encapsulation of a lipidic prodrug of dexamethasone into PLGA-PEG NPs appears as a promising strategy to improve the pharmacological profile and reduce joint inflammation in a murine model of rheumatoid arthritis.”

PLGA-PEG-folate from PolySciTech used in development of kidney-targeting nanoparticles to treat hypertension

Monday, January 10, 2022, 11:00 AM ET

High blood-pressure is a common medical problem which is exacerbated by inflammation in the lymph system and kidneys which prevents the screening out and removal of excess sodium and waste products out of the body thus reducing blood pressure. Left untreated, hypertension can lead to increased risk for heart-attack, stroke, or other severe medical problems. Recently, researchers at Texas A&M University used PLGA-PEG-folate (Cat# AI168) from PolySciTech (www.polyscitech.com) to develop kidney-targeting nanoparticles which reduce inflammation and can lead to improved sodium excretion. This research holds promise to improve therapeutic outcomes for a variety of diseases related to hypertension. Read more: Goodlett, B.L., Kang, C.S., Yoo, E., Navaneethabalakrishnan, S., Balasubbramanian, D., Love, S.E., Sims, B.M., Avilez, D.L., Tate, W., Chavez, D.R. and Baranwal, G., 2022. A Kidney-Targeted Nanoparticle to Augment Renal Lymphatic Density Decreases Blood Pressure in Hypertensive Mice. Pharmaceutics, 14(1), p.84. https://www.mdpi.com/1428566

“Abstract: Chronic interstitial inflammation and renal infiltration of activated immune cells play an integral role in hypertension. Lymphatics regulate inflammation through clearance of immune cells and excess interstitial fluid. Previously, we demonstrated increasing renal lymphangiogenesis prevents hypertension in mice. We hypothesized that targeted nanoparticle delivery of vascular endothelial growth factor-C (VEGF-C) to the kidney would induce renal lymphangiogenesis, lowering blood pressure in hypertensive mice. A kidney-targeting nanoparticle was loaded with a VEGF receptor-3-specific form of VEGF-C and injected into mice with angiotensin II-induced hypertension or LNAME-induced hypertension every 3 days. Nanoparticle-treated mice exhibited increased renal lymphatic vessel density and width compared to hypertensive mice injected with VEGF-C alone. Nanoparticle-treated mice exhibited decreased systolic blood pressure, decreased pro-inflammatory renal immune cells, and increased urinary fractional excretion of sodium. Our findings demonstrate that pharmacologically expanding renal lymphatics decreases blood pressure and is associated with favorable alterations in renal immune cells and increased sodium excretion. Keywords: kidney; lymphatics; inflammation; immunity; hypertension”

PLGA from PolySciTech used in development of in-vivo imaging nanoparticles

Tuesday, January 4, 2022, 10:59 AM ET

Near-infrared light (i.e. light at wavelengths between 800 – 2500 nm) is not readily visible to the human eye however has extremely useful properties of being able to penetrate tissue and having no physiological impact on living organisms (as compared to x-rays which can lead to damage over prolonged exposure). Incorporating a dye which responds to near-infrared light by fluorescing can be a powerful tool to image interior structures in a non-invasive manner. Recently, Researchers at University of Strasbourg used PLGA (AP082) from PolySciTech (www.polyscitech.com) to create dye-labeled nanoparticles for in-vivo imaging applications. This research holds promise for several diagnostic and therapeutic applications. Read More: Sobska, Joanna, Bohdan Andreiuk, Ilya O. Aparin, Andreas Reisch, Wojciech Krezel, and Andrey S. Klymchenko. "Counterion-insulated near-infrared dyes in biodegradable polymer nanoparticles for in vivo imaging." Nanoscale Advances (2022). https://pubs.rsc.org/en/content/articlehtml/2021/na/d1na00649e

“Abstract: Polymeric nanoparticles (NPs) are highly attractive for biomedical applications due to their potential biodegradability and capacity to encapsulate different loads, notably drugs and contrast agents. For in vivo optical bioimaging, NPs should operate in the near-infrared region (NIR) and exhibit stealth properties. In the present work, we applied the approach of ionic dye insulation with bulky hydrophobic counterions for encapsulation of near-infrared cyanine dyes (Cy5.5 and Cy7 bearing two octadecyl chains) into biodegradable polymer (PLGA) NPs. We found that at high dye loading (20–50 mM with respect to the polymer), the bulkiest fluorinated tetraphenylborate counterion minimized best the aggregation-caused quenching and improved fluorescence quantum yields of both NIR dyes, especially of Cy5.5. In addition, bulky counterions also enabled formation of small 40 nm polymeric NPs in contrast to smaller counterions. To provide them stealth properties, we prepared 40 nm dye-loaded PEGylated NPs through nanoprecipitation of synthetic PLGA–PEG block copolymer with the dye/counterion salt. The obtained NIR NPs loaded with Cy5.5 dye salt allowed in vivo imaging of wild-type mice with a good contrast after IV injection. Compared to the bare PLGA NPs, PLGA–PEG NPs exhibited significantly slower accumulation in the liver. Biodistribution studies confirmed the preferential accumulation in the liver, although PLGA and PLGA–PEG NPs could also be distributed in other organs, with the following tendency: liver > spleen > lungs > kidney > heart > testis > brain. Overall, the present work validated the counterion approach for encapsulation of NIR cyanine dyes into biodegradable polymer NPs bearing covalently attached PEG shell. Thus, we propose a simple and robust methodology for preparation of NIR fluorescent biodegradable polymer NPs, which could further improve the existing optical imaging for biomedical applications.”

PLGA from PolySciTech used in the development of oxygen-releasing tissue scaffold.

Tuesday, December 21, 2021, 12:49 PM ET

Traumatic injuries, cancer, and various other disease factors often lead to situations where portions of tissue are either lost or damaged. For cells to regrow and rebuild the damaged tissue they require a scaffold which can support their growth and metabolic requirements including access to oxygen and other nutrients. Recently, researchers at Johns Hopkins University and Baltimore Veterans Administration Medical Center utilized PLGA (cat# AP082) from PolySciTech (www.polyscitech.com) to create a 3D printed scaffold containing embedded reservoirs of oxygen. This research holds promise to improve oxygen access and growth for cells grown on tissue scaffolds. Read more: Farris, Ashley L., Dennis Lambrechts, Yuxiao Zhou, Nicholas Y. Zhang, Naboneeta Sarkar, Megan C. Moorer, Alexandra N. Rindone et al. "3D-printed oxygen-releasing scaffolds improve bone regeneration in mice." Biomaterials (2021): 121318. https://www.sciencedirect.com/science/article/pii/S0142961221006748

“Abstract: Low oxygen (O2) diffusion into large tissue engineered scaffolds hinders the therapeutic efficacy of transplanted cells. To overcome this, we previously studied hollow, hyperbarically-loaded microtanks (μtanks) to serve as O2 reservoirs. To adapt these for bone regeneration, we fabricated biodegradable μtanks from polyvinyl alcohol and poly (lactic-co-glycolic acid) and embedded them to form 3D-printed, porous poly-ε-caprolactone (PCL)-μtank scaffolds. PCL-μtank scaffolds were loaded with pure O2 at 300–500 psi. When placed at atmospheric pressures, the scaffolds released O2 over a period of up to 8 h. We confirmed the inhibitory effects of hypoxia on the osteogenic differentiation of human adipose-derived stem cells (hASCs and we validated that μtank-mediated transient hyperoxia had no toxic impacts on hASCs, possibly due to upregulation of endogenous antioxidant regulator genes. We assessed bone regeneration in vivo by implanting O2-loaded, hASC-seeded, PCL-μtank scaffolds into murine calvarial defects (4 mm diameters × 0.6 mm height) and subcutaneously (4 mm diameter × 8 mm height). In both cases we observed increased deposition of extracellular matrix in the O2 delivery group along with greater osteopontin coverages and higher mineral deposition. This study provides evidence that even short-term O2 delivery from PCL-μtank scaffolds may enhance hASC-mediated bone tissue regeneration.”

PLGA from PolySciTech used in development of bioinspired surgical glue

Tuesday, December 21, 2021, 12:48 PM ET

A common problem in surgical applications is sealing tissues together which are separated either due to an incision or due to patient trauma. Although sutures and staples can be used to mechanically hold tissue together there are certain locations and applications where the physical constraints are too tight, the tissue is too weak, or these mechanical methods are inappropriate for other reasons. Any glue utilized for this application must possess biocompatibility, biodegradability, and the ability to seal to wet, biological surfaces. Recently, researchers at University of Texas at Arlington and University of Texas Southwestern Medical Center used PLGA (cat# AP036) from PolySciTech (www.polyscitech.com) to test a variety of nanocomposite adhesion strength. This research holds promise to provide for improved surgical techniques in the future. Read more: Pandey, Nikhil, Luis Soto-Garcia, Serkan Yaman, Aneetta Kuriakose, Andres Urias Rivera, Valinda Jones, Jun Liao, Philippe Zimmern, Kytai T. Nguyen, and Yi Hong. "Polydopamine nanoparticles and hyaluronic acid hydrogels for mussel-inspired tissue adhesive nanocomposites." Materials Science and Engineering: C (2021): 112589. https://www.sciencedirect.com/science/article/pii/S0928493121007293

“Highlights: Mussel-inspired hydrogels are promising for tissue attachment under wet conditions. Nanoparticles addition can enhance the adhesive strength of a hydrogel adhesive. Polydopamine nanoparticles and catechol-modified hyaluronic acid are combined. The nanocomposite showed improved adhesive strength and good cytocompatibility. The adhesive has opportunities to be utilized as a tissue glue for biomedicine. Abstract: Bioadhesives are intended to facilitate the fast and efficient reconnection of tissues to restore their functionality after surgery or injury. The use of mussel-inspired hydrogel systems containing pendant catechol moieties is promising for tissue attachment under wet conditions. However, the adhesion strength is not yet ideal. One way to overcome these limitations is to add polymeric nanoparticles to create nanocomposites with improved adhesion characteristics. To further enhance adhesiveness, polydopamine nanoparticles with controlled size prepared using an optimized process, were combined with a mussel-inspired hyaluronic acid (HA) hydrogel to form a nanocomposite. The effects of sizes and concentrations of polydopamine nanoparticles on the adhesive profiles of mussel-inspired HA hydrogels were investigated. Results show that the inclusion of polydopamine nanoparticles in nanocomposites increased adhesion strength, as compared to the addition of poly (lactic-co-glycolic acid) (PLGA), and PLGA-(N-hydroxysuccinimide) (PLGA-NHS) nanoparticles. A nanocomposite with demonstrated cytocompatibility and an optimal lap shear strength (47 ± 3 kPa) was achieved by combining polydopamine nanoparticles of 200 nm (12.5% w/v) with a HA hydrogel (40% w/v). This nanocomposite adhesive suggests its potential as a tissue glue for biomedical applications.”

PLGA-PEG-azide from PolySciTech used in development of decorated nanoparticle for cancer immunotherapy

Tuesday, December 21, 2021, 12:48 PM ET

Cancer cells and tumors typically apply a wide variety of strategies to evade the human immune system which makes treatment of them very difficult. Induction of a targeted immunoresponse against tumors and cancer cells can provide for a promising opportunity to leverage the power of the human immune system towards elimination of cancer. Researchers at Chinese Academy of Sciences, Jiangnan University, and Shenzhen University (China) used mPEG-PLGA (cat# AK102) and PLGA-PEG-N3 (cat# AI091) from PolySciTech (www.polyscitech.com) to create immunotherapy initiating nanoparticles by Pickering emulsion methodologies. This research holds promise to provide for improved therapies against cancer. Read more: Du, Yiqun, Tiantian Song, Jie Wu, Xiao-Dong Gao, Guanghui Ma, Yuchen Liu, and Yufei Xia. "Engineering mannosylated pickering emulsions for the targeted delivery of multicomponent vaccines." Biomaterials 280 (2022): 121313. https://www.sciencedirect.com/science/article/abs/pii/S0142961221006694

“Abstract: While research on cancer vaccines has made great strides in the field of immunotherapy, the targeted delivery of multiple effective components (rational-tailored antigens and adjuvants) remains a challenge. Here, we utilized the unique hierarchical structures of Pickering emulsions (particles, oil core, and water-oil interface) to develop mannosylated (M) Pickering emulsions (PE) that target antigen presenting cells and synergistically deliver antigenic peptides and the TLR9 agonist CpG (C) as an enhanced cancer vaccine (MPE-C). We chemically linked mannose residues to PLGA/PLAG-PEG nanoparticles and produced a dense array of mannose on the nanopatterned surface of Pickering emulsions, allowing for increased cellular targeting. Together with the inherent deformability of the oily core, MPE-C increased the droplet-cellular contact area and provoked the cellular recognition of mannose and CpG for enhanced immune activation. We found that MPE-C attracted a large number of APCs to the local site of administration, evidently increasing cellular uptake and activation. Additionally, we observed increased antigen-specific cellular immune responses, with potent anti-tumor effects against both E.G7-OVA and B16-MUCI tumors. Furthermore, MPE-C combined with PD-1 antibodies produced a significant tumor regression, resulting in synergistic increases in anti-tumor effects. Thus, through the strategic loading of mannose, antigens, and CpG, Pickering emulsions could serve as a targeted delivery platform for enhanced multicomponent cancer vaccines.”

PLGA from PolySciTech used in research on swelling of hydroxyapatite-PVA bone graft material

Tuesday, December 14, 2021, 3:23 PM ET

Bone graft materials are compounds and mixtures which provide a structure for bone cells (osteoblasts) to grow on and reform bone. This is a promising field of research for repairing bone after surgery or traumatic accident (car-crash, etc.). Recently, researchers at Universitas Brawijaya (Indonesia) used PLGA from PolySciTech (www.polyscitech.com) to create composite materials of hydroxyapatite-PVA-PLGA as a potential tissue graft and measure the resultant swelling as a means of determining the porosity and structure of the composites to evaluate their usage as bone graft material. This research holds promise to provide for improved tissue repair in the future. Istikharoh, Feni, Hidayat Sujuti, Edi Mustamsir, and Astika Swastirani. "Study on swelling behaviour of HANP/PVA composites with adding PLGA for alveolar ridge preservation." Journal of Dentomaxillofacial Science, v. 6, n. 3, p. 197-199, dec. 2021 https://jdmfs.org/index.php/jdmfs/article/view/998

“Objective: The aim of this study was to compare the swelling behaviour of Hand Polyvinyl Acetate/Polyvinyl alcohol (HANP/PVA) and HANP/PVA/Poly Lactic-co-Glycolic Acid (PLGA) composites. Material and Methods: This study was divided into 2 groups, HANP/PVA and HANP/PLGA/PVA composites which prepared by freeze drying methods. HANP 20% (w/w) was combined with PLGA 20% (w/w) and dissolved in PVA solution at 50oC. Swelling behaviour was obtained by measured initial weight (Wi) and the weight of composites after immersing in PBS pH 7.4; 37oC for 7 days (swollen weight (Ws)). Statistical analysis based on Independent T-test (p<0.05). Results: The Wi of HANP/PVA and HANP/PLGA/PVA composites are 467±4.73 and 292±9.52. The Ws of HANP/PVA and HANP/PLGA/PVA composites are 897±26.61 and 860±32.36. Furthermore, the water retention of HANP/PVA composite is 92.07% (p<0.05) and HANP/PLGA/PVA composite is 194.52% (p<0.05). Conclusion: The addition of PLGA enhance swelling behaviour of HANP/PVA composites. The strong interaction between HANP and PVA decrease the swelling re. HANP is inert in nature, but the combination of HANP/PLGA/PVA can be a good substitute for alveolar preservation.”

PLGA-PEG-azide from PolySciTech used in development of nanoparticle-based diabetes treatment

Tuesday, December 7, 2021, 4:30 PM ET

In Type-1 diabetes an improper immune response attacks insulin-producing beta cells and destroys them leading to a dependence on external insulin. Generation of immune tolerance towards the B cells can prevent diabetes. Recently, researchers at University of North Carolina Chapel Hill and University of Texas Southwestern Medical Center used PLGA-PEG-Azide (Cat# AI091) from PolySciTech (www.polyscitech.com) to create a diabetes treatment which reduces immune attack against insulin-producing cells. This research holds promise to provide for a prophylactic against diabetes. Read more: Au, Kin Man, Roland Tisch, and Andrew Z. Wang. "In Vivo Bioengineering of Beta Cells with Immune Checkpoint Ligand as a Treatment for Early-Onset Type 1 Diabetes Mellitus." ACS nano (2021). https://pubs.acs.org/doi/abs/10.1021/acsnano.1c07538

“Abstract: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by autoreactive T cells targeting the insulin-producing beta (β) cells. Despite advances in insulin therapy, T1DM still leads to high morbidity and mortality in patients. A key focus of T1DM research has been to identify strategies that re-establish self-tolerance and suppress ongoing autoimmunity. Here, we describe a strategy that utilizes pretargeting and glycochemistry to bioengineer β cells in situ to induce β-cell-specific tolerance. We hypothesized that β-cell-targeted Ac4ManNAz-encapsulated nanoparticles deliver and establish β cells with high levels of surface reactive azide groups. We further theorized that administration of a dibenzylcyclooctyne (DBCO)-functionalized programmed death-ligand 1 immunoglobulin fusion protein (PD-L1-Ig) can be readily conjugated to the surface of native β cells. Using nonobese diabetic (NOD) mice, we demonstrated that our strategy effectively and selectively conjugates PD-L1 onto β cells through bioorthogonal stain-promoted azide–alkyne cycloaddition. We also showed that the in vivo functionalized β cells simultaneously present islet-specific antigen and PD-L1 to the engaged T cells, reversing early onset T1DM by reducing IFN-gamma expressing cytotoxic toxic T cells and inducing antigen-specific tolerance. KEYWORDS: type 1 diabetes mellitus immune checkpoints pretargeting stain-promoted azide−alkyne cycloaddition immunotolerance”

Fluorescent PLGA from PolySciTech used in development of mRNA delivery nanoparticles

Tuesday, December 7, 2021, 4:29 PM ET

The promise of mRNA based nanotherapeutics has been partially realized in the development and deployment of related Covid vaccine formulations. This powerful technique holds the ability to induce the body to create highly specific proteins in a particular manner. The therapeutic applications of this technique are just starting to come to light. Recently, researchers at AstraZeneca utilized fluorescent PLGA-FPR648 (Cat# AV008) from PolySciTech (www.polyscitech.com) to create trackable nanoparticles. This research holds promise to provide for improved mRNA therapies in the future. Read more: Meyer, Randall A., G. Patrick Hussmann, Norman C. Peterson, Jose Luis Santos, and Anthony D. Tuesca. "A scalable and robust cationic lipid/polymer hybrid nanoparticle platform for mRNA delivery." International Journal of Pharmaceutics (2021): 121314. https://www.sciencedirect.com/science/article/abs/pii/S0378517321011200

“Abstract: mRNA based gene therapies hold the potential to treat multiple diseases with significant advantages over DNA based therapies, including rapid protein expression and minimized risk of mutagenesis. However, successful delivery of mRNA remains challenging, and clinical translation of mRNA therapeutics has been limited. This study investigated the use of a lipid/polymer hybrid (LPH) nanocarrier for mRNA, designed to address key delivery challenges and shuttle mRNA to targeted tissues. LPH nanocarriers were synthesized using a scalable microfluidic process with a variety of material compositions and mRNA loading strategies. Results show that a combination of permanently ionized and transiently, pH-dependent ionizable cationic lipids had a synergistic effect upon on mRNA gene translation, when compared to each lipid independently. Upon intravenous administration, particles with adsorbed mRNA outperformed particles with encapsulated mRNA for protein expression in the lungs and the spleen despite significant LPH nanoparticle localization to the liver. In contrast, encapsulated particles had higher localized expression when injected intramuscularly with protein expression detectable out to 12 days post injection. Intramuscular administration of particles with OVA mRNA resulted in robust humoral immune response with encapsulated outperforming adsorbed particles in terms of antibody titers at 28 days. These results demonstrate LPH nanocarriers have great potential as a vehicle for mRNA delivery and expression in tissues and that tissue expression and longevity can be influenced by LPH composition and route of administration.”

mPEG-PLGA from PolySciTech used in research on the effect of LA:GA Sequencing

Tuesday, November 23, 2021, 8:42 AM ET

During the normal ring-opening polymerization of PLGA, the glycolide monomer typically reacts faster and more readily than the lactide monomer leading to non-random distribution of monomers along the polymer chain. This process competes with transesterification and other reactive processes in polymer manufacturing which act to improve randomness along the chain. Recently, researchers at Purdue University developed a novel method to make small quantities of mPEG-PLGA with precisely controlled monomer distribution. They used mPEG-PLGA (Cat# AK010) from PolySciTech (www.polyscitech.com) (manufactured using conventional bulk-melt ring-opening polymerization) to compare the various batches they had made. In addition to traditional PLGA offerings, Akina has recently begun adding products of PLGA alternating LA:GA based on 3-methylglycolide monomer (e.g. cat# AP279 – AP281). This research holds promise to provide a more mechanistic understanding of PLGA sequencing effect on the polymer properties. Read more: Yoo, Jin, Dhushyanth Viswanath, and You-Yeon Won. "Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties." ACS Macro Letters 10 (2021): 1510-1516. https://pubs.acs.org/doi/abs/10.1021/acsmacrolett.1c00637

“Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(d,l-lactic-co-glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequence-controlled “uniform PLGA” polymers through control of the rate of comonomer addition. Using this method, a series of PEG–PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol–gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.”

PLGA-PEG-COOH from PolySciTech used in development of carborane-loaded nanoparticles for prostate cancer treatment

Tuesday, November 16, 2021, 4:31 PM ET

PSMA is a marker which is overexpressed on cancer cells and can provide an attractive target for ligand-based therapies. Recently researchers at University of California San Francisco used PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create PSMA-targetting nanoparticles loaded with carborane for boron neutron capture therapy against prostate cancer. This research holds promise to improve therapeutic options for cancer. Read more: Meher, Niranjan, Kyounghee Seo, Sinan Wang, Anil P. Bidkar, Miko Fogarty, Suchi Dhrona, Xiao Huang et al. "Synthesis and Preliminary Biological Assessment of Carborane-Loaded Theranostic Nanoparticles to Target Prostate-Specific Membrane Antigen." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c16383

“Boron neutron capture therapy (BNCT) is an encouraging therapeutic modality for cancer treatment. Prostate-specific membrane antigen (PSMA) is a cell membrane protein that is abundantly overexpressed in prostate cancer and can be targeted with radioligand therapies to stimulate clinical responses in patients. In principle, a spatially targeted neutron beam together with specifically targeted PSMA ligands could enable prostate cancer-targeted BNCT. Thus, we developed and tested PSMA-targeted poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles (NPs) loaded with carborane and tethered to the radiometal chelator deferoxamine B (DFB) for simultaneous positron emission tomography (PET) imaging and selective delivery of boron to prostate cancer. Monomeric PLGA-b-PEGs were covalently functionalized with either DFB or the PSMA ligand ACUPA. Different nanoparticle formulations were generated by nanoemulsification of the corresponding unmodified and DFB- or ACUPA-modified monomers in varying percent fractions. The nanoparticles were efficiently labeled with 89Zr and were subjected to in vitro and in vivo evaluation. The optimized DFB(25)ACUPA(75) NPs exhibited strong in vitro binding to PSMA in direct binding and competition radioligand binding assays in PSMA(+) PC3-Pip cells. [89Zr]DFB(25) NPs and [89Zr]DFB(25)ACUPA(75) NPs were injected to mice with bilateral PSMA(−) PC3-Flu and PSMA(+) PC3-Pip dual xenografts. The NPs demonstrated twofold superior accumulation in PC3-Pip tumors to that of PC3-Flu tumors with a tumor/blood ratio of 25; however, no substantial effect of the ACUPA ligands was detected. Moreover, fast release of carborane from the NPs was observed, resulting in a low boron delivery to tumors in vivo. In summary, these data demonstrate the synthesis, characterization, and initial biological assessment of PSMA-targeted, carborane-loaded PLGA-b-PEG nanoparticles and establish the foundation for future efforts to enable their best use in vivo.”

PLGA-NH2 from PolySciTech used in testing nanoparticles for platinum-based anticancer therapy

Tuesday, November 16, 2021, 4:29 PM ET

Cisplatin is the first FDA approved metal-based drug for treatment of solid tumors as it uses platinum as an active agent. In the blood stream, however, it reacts with glutathione which diminishes its effectiveness. Recently, researchers at City University of New York used PLGA-NH2 (AI010) to make Cy5.5 labeled nanoparticles for tracking purposes as part of their research in making nanoparticles for delivery of cisplatin. This research holds promise for improving treatments against cancer. Read more: Marek T. Wlodarczyk “Enhanced Platinum (II) Drug Delivery for Anti-cancer Therapy” PhD Dissertation City University of New York, 2021 https://academicworks.cuny.edu/cgi/viewcontent.cgi?article=5668&context=gc_etds

“Over the years, anti-cancer therapies have improved the overall survival rate of patients. Nevertheless, the traditional free drug therapies still suffer from side effects and systemic toxicity, resulting in low drug dosages in the clinic. This often leads to suboptimal drug concentrations reaching cancer cells, contributing to treatment failure and drug resistance. Among available anticancer therapies, metallodrugs are of great interest. Platinum (II)-based agents are highly potent and are used to treat many cancers, including ovarian cancer (OC). Cisplatin (cisdiaminedichloroplatinum (II)) is the first Food and Drug Administration (FDA)-approved metallodrug for treatment of solid tumors, and its mechanism of action is based on inhibition of cancer cell replication via binding to nuclear DNA. However, circulating cisplatin binds to glutathione and other proteins in the blood compartment, diminishing the concentration of the free drug available for therapy. Also, highly potent cisplatin is associated with severe side effects, limiting the dosage of Pt(II) that can be administered in the clinic. The next generation Pt(II) drugs aim at sustaining the same effectiveness while improving systemic toxicity. Carboplatin is a second-generation Pt-based agent approved by the Food and Drug Administration (FDA). Slower hydrolysis times for carboxylate ligands in carboplatin, compared to rather fast times for chlorine ligands in cisplatin, lead to longer blood circulation times and lesser side effects. The therapeutic effect of carboplatin is comparable with cisplatin in some tumors, but it requires higher drug dosages, and the survival rate did not improve.”

PLGA from PolySciTech used in development of technetium-loaded nanoparticles for theranostic applications

Thursday, October 28, 2021, 8:47 AM ET

The primary benefit and complication of nanoparticles is that they are small. The same diminutive size which allows them to flow freely through the circulatory system also makes their detection and localization difficult. Recently, researchers at University of Rome (Italy) used PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create technetium-labelled nanoparticles. These radio-labelled nanoparticles enabled discrete and accurate imaging of the localization of particles in an animal model. This research holds promise to improve nanobased therapies against several disease states including cancer. Read More: Varani, Michela, Giuseppe Campagna, Valeria Bentivoglio, Matteo Serafinelli, Maria Luisa Martini, Filippo Galli, and Alberto Signore. "Synthesis and Biodistribution of 99mTc-Labeled PLGA Nanoparticles by Microfluidic Technique." Pharmaceutics 13, no. 11 (2021): 1769. https://www.mdpi.com/1999-4923/13/11/1769

“The aim of present study was to develop radiolabeled NPs to overcome the limitations of fluorescence with theranostic potential. Synthesis of PLGA-NPs loaded with technetium-99m was based on a Dean-Vortex-Bifurcation Mixer (DVBM) using an innovative microfluidic technique with high batch-to-batch reproducibility and tailored-made size of NPs. Eighteen different formulations were tested and characterized for particle size, zeta potential, polydispersity index, labeling efficiency, and in vitro stability. Overall, physical characterization by dynamic light scattering (DLS) showed an increase in particle size after radiolabeling probably due to the incorporation of the isotope into the PLGA-NPs shell. NPs of 60 nm (obtained by 5:1 PVA:PLGA ratio and 15 mL/min TFR with 99mTc included in PVA) had high labeling efficiency (94.20 ± 5.83%) and > 80% stability after 24 h and showed optimal biodistribution in BALB/c mice. In conclusion, we confirmed the possibility of radiolabeling NPs with 99mTc using the microfluidics and provide best formulation for tumor targeting studies. Keywords: radiolabeled nanoparticles; poly (lactic-co-glycolic acid) (PLGA); nuclear medicine; microfluidics”

PLGA from PolySciTech used in research on 3D printed graphene based on a temporary nickel scaffold

Thursday, October 28, 2021, 8:47 AM ET

Typically, the biodegradability of PLGA is utilized in a medical sense to create structures which slowly break down over time in the human body in a non-toxic manner for tissue engineering or drug-delivery applications. PLGA’s degradation, however, is hydrolysis and occurs in general upon contact with any water proceeding faster in acid or alkali conditions. This allows PLGA to be used in engineering applications as a temporary structure. Recently, researchers at University of Cincinnati and A&T North Carolina State University used PLGA (PolyVivo cat# AP234) from PolySciTech (www.polyscitech.com) as a temporary binder for nickel particles as part of development of a novel 3D-printed catalyst system for graphene structure creation. This research holds promise to improve capabilities of forming complex structures from reinforced materials. Read more: Kondapalli, Vamsi Krishna Reddy, Xingyu He, Mahnoosh Khosravifar, Safa Khodabakhsh, Boyce Collins, Sergey Yarmolenko, Ashley Paz y Puente, and Vesselin Shanov. "CVD Synthesis of 3D-Shaped 3D Graphene Using a 3D-Printed Nickel–PLGA Catalyst Precursor." ACS Omega (2021). https://pubs.acs.org/doi/abs/10.1021/acsomega.1c04072

“Earlier, various attempts to develop graphene structures using chemical and nonchemical routes were reported. Being efficient, scalable, and repeatable, 3D printing of graphene-based polymer inks and aerogels seems attractive; however, the produced structures highly rely on a binder or an ice support to stay intact. The presence of a binder or graphene oxide hinders the translation of the excellent graphene properties to the 3D structure. In this communication, we report our efforts to synthesize a 3D-shaped 3D graphene (3D2G) with good quality, desirable shape, and structure control by combining 3D printing with the atmospheric pressure chemical vapor deposition (CVD) process. Direct ink writing has been used in this work as a 3D-printing technique to print nickel powder–PLGA slurry into various shapes. The latter has been employed as a catalyst for graphene growth via CVD. Porous 3D2G with high purity was obtained after etching out the nickel substrate. The conducted micro CT and 2D Raman study of pristine 3D2G revealed important features of this new material. The interconnected porous nature of the obtained 3D2G combined with its good electrical conductivity (about 17 S/cm) and promising electrochemical properties invites applications for energy storage electrodes, where fast electron transfer and intimate contact with the active material and with the electrolyte are critically important. By changing the printing design, one can manipulate the electrical, electrochemical, and mechanical properties, including the structural porosity, without any requirement for additional doping or chemical postprocessing. The obtained binder-free 3D2G showed a very good thermal stability, tested by thermo-gravimetric analysis in air up to 500 °C. This work brings together two advanced manufacturing approaches, CVD and 3D printing, thus enabling the synthesis of high-quality, binder-free 3D2G structures with a tailored design that appeared to be suitable for multiple applications.”

PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy

Monday, October 25, 2021, 1:17 PM ET

PEG-PLA from PolySciTech used in development of galbanic-acid based colon-cancer therapy

Galbanic acid (compound extracted from Asafoetida herb) has demonstrated apoptotic activity against cancer cells in the past. Recently, researchers at Mashhad University of Medical Sciences utilized PEG-PLA (PolyVivo cat# AK054) to create galbanic acid-loaded nanoparticles. They tested these for efficacy and safety both in-vitro as well as in an in-vivo model. This research may provide for improved treatments of colon cancer in the future. Read more: Hashemi, Maryam, Maryam Afsharzadeh, Maryam Babaei, Mahboubeh Ebrahimian, Khalil Abnous, and Mohammad Ramezani. "Enhanced anticancer efficacy of docetaxel through galbanic acid encapsulated into PLA-PEG nanoparticles in treatment of colon cancer, in vitro and in vivo study." Journal of Bioactive and Compatible Polymers (2021): 08839115211053922. https://journals.sagepub.com/doi/abs/10.1177/08839115211053922

“Abstract: Cancer is one of the most leading causes of human mortality and despite outstanding breakthrough in introducing new therapeutic approaches, the clinical outcomes are disappointing. Therefore, extensive research in design and preparation of more efficient drug delivery systems can open a window to shine light into the therapeutic modality. In this study, we evaluated the effect of galbanic acid (GBA) encapsulated into PLA-PEG nanoparticles (NPs) to enhanced anticancer efficacy of docetaxel (DOC) for the treatment of colon cancer. Prepared NPs were characterized by different methods in terms of size, zeta potential, and drug loading capacity. MTT assay was used to investigate the anti-proliferation of GBA-loaded PEG-PLA NPs along with DOC. The therapeutic efficacy of PEG-PLA@GBA NPs & DOC was further investigated in C26 tumor-bearing BALB/c mice model. The resulting NPs were narrowly distributed (PDI = 0.06) with the mean diameter of 148 ± 9 nm with somewhat negative charge. GBA were efficiently loaded into mPEG-PLA NPs with encapsulation efficiency of about 40% ± 3. Cytotoxicity studies showed that NPs loaded with GBA and fixed concentration of docetaxel (20 nM) have higher toxicity (IC50 = 6 ± 1.8 µM) than either PEG-PLA@GBA (IC50 = 8 ± 1.2 µM) or free GBA (IC50 = 15 ± 3.5 µM) in C26 cells. In vivo studies revealed a synergistic effect of PEG-PLA@GBA NPs and DOC on tumor growth inhibition and survival rate in comparison with monotherapy approach. Keywords: Galbanic acid, docetaxel, PEG-PLA nanoparticles, colon cancer, combination therapy”

PLGA from PolySciTech used in development of microelectrode array for non-opioid pain management

Tuesday, October 5, 2021, 10:55 AM ET

Current pain management strategies typically rely on opioid medications which have a high propensity to lead to addiction. Opioid addiction has become a world-wide societal problem in recent years requiring research into opioid-free pain relief strategies. Recently, researchers at University of Washington used mPEG-PLGA (Cat# AK106) and PLGA (Cat# AP045) from PolySciTech (www.polyscitech.com) to create curcumin-loaded nanoparticles as part of development of nanoparticle loaded microelectrode array for pain management. This research holds promise to improve pain management strategies in the future. Read more: Xu, Nuo. "Nanoparticle loaded implantable flexible microelectrode arrays for pain management after spinal cord surgery." PhD diss., University of Washington, 2021. https://search.proquest.com/openview/530e9f32e470658b868b55aabf7b6312/1?pq-origsite=gscholar&cbl=18750&diss=y

“Abstract: The health care system currently faces significant burden with abuse of opioids and an unmet market need for pain management after surgery and injury. A drug delivery device that can improve drug delivery efficiency, increase drug duration of action, and deliver anesthetics topically with low toxicity is needed. Implantable flexible microelectrode arrays are widely used after spinal cord injury for pain mainagement, but they have limitations in improving the solubility, bioavailability, and permeability of drug. Biodegradable polymeric nanoparticles have highly tailorable physicochemical properties, and with incorporation on microelectrode arrays (MEAs), may increase the physical and chemical properties of therapeutic agents such as permeability, solubility and bioavailability. However, drug-loaded biodegradable nanoparticle-polypyrrole coated MEA for drug delivery has not been reported in literature. Therefore, we investigate the use of biodegradable nanoparticles for controlled release of bupivacaine hydrochloride from MAEs for pain management following spinal cord surgery. Bupivacaine hydrochloride, a commonly used FDA-approved anesthetic, is chosen as the model drug due to its nerve block and anti-inflammatory effects. This work starts with the exploration of the relationship between the formulation parameters of biodegradable nanoparticles and their physicochemical properties. Then, the bupivacaine hydrochloride loaded nanoparticles are formulated, and the drug loading of the nanoparticles is explored through iterating formulation parameters. Thereafter, nanoparticles with different surface charges are loaded on the MAEs to determine the relationship between the surface charge of nanoparticles and the release behavior of these nanoparticles. Finally, the release behavior of the nanoparticles from the MAEs is used as a guide to further optimize the bupivacaine hydrochloride loaded nanoparticle formulation.”

PLA from PolySciTech used in development of Doxycycline/miR-21i co-delivery nanoparticle for cancer treatment

Monday, September 27, 2021, 3:00 PM ET

One potential method for treatment of cancer is by reducing the amount of microRNA that the cancer can produce in addition to conventional chemotherapy. Recently, researchers at University of Cincinnati used PLA (AP128) from PolySciTech to create multi-drug loaded nanoparticles. This treatment holds promise to improve therapy against cancer. Rear more: Sriram, Vishnu, and Joo-Youp Lee. "Calcium Phosphate-Polymeric Nanoparticle System for Co-delivery of microRNA-21 Inhibitor and Doxorubicin." Colloids and Surfaces B: Biointerfaces (2021): 112061. https://www.sciencedirect.com/science/article/abs/pii/S0927776521005051

“Highlights: NPs successfully achieved sequential delivery of miR-21 inhibitor followed by Dox. NPs delivered miR-21 inhibitor to the cytoplasm through endosomal escape. NPs downregulated miR-21 levels and upregulated PTEN levels. Abstract: NPs showed enhanced cytotoxicity against MDA-MB-231 and A549 cells. Abstract: Targeted combination therapy has shown promise to achieve maximum therapeutic efficacy by overcoming drug resistance. MicroRNA-21 (miR-21) is frequently overexpressed in various cancer types including breast and non-small cell lung cancer and its functions can be inhibited by miR inhibitor (miR-21i). A combination of miR-21i and a chemo drug, doxorubicin (Dox), can provide synergistic effects. Here, we developed a calcium phosphate (CaP)-coated nanoparticle (NP) formulation to co-deliver miR-21i along with Dox. This NP design can be used to deliver the two agents with different physiochemical properties. The NP formulation was optimized for particle size, polydispersity, Dox loading, and miR-21i loading. The NP formulation was confirmed to downregulate miR-21 levels and upregulate tumor suppressor gene levels. The cytotoxic efficacy of the combined miR-21i and Dox-containing NPs was found to be higher than that of Dox. Therefore, the CaP-coated hybrid lipid-polymeric NPs hold potential for the delivery of miR-21i and Dox. Keywords: Polymeric nanoparticles Calcium phosphate microRNA-21 inhibitor Doxorubicin Co-delivery Combination therapy”

mPEG-PLGA from PolySciTech used in development of microfluidic nanoparticles for delivery of peptides

Friday, September 24, 2021, 4:10 PM ET

Peptides represents an important and useful class of drugs which are limited due to their rapid breakdown in the blood stream. Recently researchers from The University of Queensland, National Center for Nanoscience and Technology, and Southern University of Science and Technology (China), mPEG-PLGA (Cat# AK026) from PolySciTech (www.polyscitech.com) was used for peptide delivery. This research holds promise to improve the longevity of peptide drugs thus extending their usefulness. Read More: Han, Felicity Y., Weizhi Xu, Vinod Kumar, Cedric S. Cui, Xaria Li, Xingyu Jiang, Trent M. Woodruff, Andrew K. Whittaker, and Maree T. Smith. "Optimisation of a Microfluidic Method for the Delivery of a Small Peptide." Pharmaceutics 13, no. 9 (2021): 1505. https://www.mdpi.com/1276894

“Abstract: Peptides hold promise as therapeutics, as they have high bioactivity and specificity, good aqueous solubility, and low toxicity. However, they typically suffer from short circulation half-lives in the body. To address this issue, here, we have developed a method for encapsulation of an innate-immune targeted hexapeptide into nanoparticles using safe non-toxic FDA-approved materials. Peptide-loaded nanoparticles were formulated using a two-stage microfluidic chip. Microfluidic-related factors (i.e., flow rate, organic solvent, theoretical drug loading, PLGA type, and concentration) that may potentially influence the nanoparticle properties were systematically investigated using dynamic light scattering and transmission electron microscopy. The pharmacokinetic (PK) profile and biodistribution of the optimised nanoparticles were assessed in mice. Peptide-loaded lipid shell-PLGA core nanoparticles with designated size (~400 nm) and a sustained in vitro release profile were further characterized in vivo. In the form of nanoparticles, the elimination half-life of the encapsulated peptide was extended significantly compared with the peptide alone and resulted in a much higher distribution into the lung. These novel nanoparticles with lipid shells have considerable potential for increasing the circulation half-life and improving the biodistribution of therapeutic peptides to improve their clinical utility, including peptides aimed at treating lung-related diseases. Keywords: drug delivery system; nanoparticles; poly (lactic-co-glycolic acid) (PLGA); microfluidic; pharmacokinetics (PK) and biodistribution”

PLGA from PolySciTech Used in development of intracellular delivery systems.

Friday, September 24, 2021, 4:09 PM ET

The ability to deliver medicines and genetic materials into a cell can be a powerful tool to treat disease. Recently, researchers at University of Connecticut and University of Iowa purchased PLGA from PolySciTech (www.polyscitech.com) to create poly(histidine)-PLGA mixed nanoparticles. They researched the use of this as a way to deliver nanoparticles into cells. This research holds promise to improve intracellular delivery. Read more: Wahane, Aniket, Shipra Malik, Kuo-Chih Shih, Ravinder Reddy Gaddam, Chaohao Chen, Yun Liu, Mu-Ping Nieh, Ajit Vikram, and Raman Bahal. "Dual-Modality Poly-l-histidine Nanoparticles to Deliver Peptide Nucleic Acids and Paclitaxel for In Vivo Cancer Therapy." ACS Applied Materials & Interfaces (2021). https://pubs.acs.org/doi/abs/10.1021/acsami.1c11981

“Abstract: Cationic polymeric nanoformulations have been explored to increase the transfection efficiency of small molecules and nucleic acid-based drugs. However, an excessive positive charge density often leads to severe cell and tissue-based toxicity that restricts the clinical translation of cationic polymeric nanoformulations. Herein, we investigate a series of cationic poly(lactic-co-glycolic acid) (PLGA)-histidine-based nanoformulations for enhanced cytoplasmic delivery with minimal toxicity. PLGA/poly-l-histidine nanoparticles show promising physico-biochemical features and transfection efficiency in a series of in vitro and cell culture-based studies. Further, the use of acetone/dichloromethane as a solvent mixture during the formulation process significantly improves the morphology and size distribution of PLGA/poly-l-histidine nanoparticles. PLGA/poly-l-histidine nanoformulations undergo clathrin-mediated endocytosis. A contrast-matched small-angle neutron scattering experiment confirmed poly-l-histidine’s distribution on the PLGA nanoformulations. PLGA/poly-l-histidine formulations containing paclitaxel as a small molecule-based drug and peptide nucleic acids targeting microRNA-155 as nucleic acid analog are efficacious in in vitro and in vivo studies. PLGA/poly-l-histidine NPs significantly decrease tumor growth in PNA-155 (∼6 fold) and paclitaxel (∼6.5 fold) treatment groups in a lymphoma cell line derived xenograft mice model without inducing any toxicity. Hence, PLGA/poly-l-histidine nanoformulations exhibit substantial transfection efficiency and are safe to deliver reagents ranging from small molecules to synthetic nucleic acid analogs and can serve as a novel platform for drug delivery. KEYWORDS: poly-l-histidine PLGA nanoparticles proton-sponge effect microRNAs”

PLGA from PolySciTech used in development of Long-Acting implant for vaccination against Covid-19 variants

Thursday, September 16, 2021, 2:32 PM ET

The way in which an antigen or other structure is presented to the immune system has an effect on how strong the immune system develops a response against that particular antigen. Notably, for vaccination, it is optimal to provide an antigen to the immune system over an extended time to maximize vaccine efficacy. Recently, researchers at University of California, San Diego loaded antigens that are conserved between variants of concern (i.e. similar antigen structures that show up in multiple viral variants despite their other differences) into a PLGA/PEG rod extrusion mix comprised of PLGA (cat# AP041) from PolySciTech (www.polyscitech.com) to create a slow-release antigen rod which was both stable at room temperature and eliminated the need for follow-up innoculations. This research holds promise for improving protections against both the current pandemic as well as future pandemic’s yet to come. Read more: Ortega-Rivera, Oscar A., Matthew D. Shin, Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso et al. "Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices." Journal of the American Chemical Society (2021). https://pubs.acs.org/doi/abs/10.1021/jacs.1c06600

“The COVID-19 pandemic highlights the need for platform technologies enabling rapid development of vaccines for emerging viral diseases. The current vaccines target the SARS-CoV-2 spike (S) protein and thus far have shown tremendous efficacy. However, the need for cold-chain distribution, a prime-boost administration schedule, and the emergence of variants of concern (VOCs) call for diligence in novel SARS-CoV-2 vaccine approaches. We studied 13 peptide epitopes from SARS-CoV-2 and identified three neutralizing epitopes that are highly conserved among the VOCs. Monovalent and trivalent COVID-19 vaccine candidates were formulated by chemical conjugation of the peptide epitopes to cowpea mosaic virus (CPMV) nanoparticles and virus-like particles (VLPs) derived from bacteriophage Qβ. Efficacy of this approach was validated first using soluble vaccine candidates as solo or trivalent mixtures and subcutaneous prime-boost injection. The high thermal stability of our vaccine candidates allowed for formulation into single-dose injectable slow-release polymer implants, manufactured by melt extrusion, as well as microneedle (MN) patches, obtained through casting into micromolds, for prime-boost self-administration. Immunization of mice yielded high titers of antibodies against the target epitope and S protein, and data confirms that antibodies block receptor binding and neutralize SARS-CoV and SARS-CoV-2 against infection of human cells. We present a nanotechnology vaccine platform that is stable outside the cold-chain and can be formulated into delivery devices enabling single administration or self-administration. CPMV or Qβ VLPs could be stockpiled, and epitopes exchanged to target new mutants or emergent diseases as the need arises.”

PLGA from PolySciTech used in bacteria-mediated drug-delivery system development

Wednesday, September 15, 2021, 2:52 PM ET

There are many ways to make drug-delivery systems and for operating at such small-scale often it is advantageous to employ microorganisms to help with this. Recently, researchers at Virginia Tech used PLGA (Cat# AP082) from PolySciTech (www.polyscitech.com) to create bacteria-attaching nanobeads for using the bacteria to help deliver drug molecules. This research represents a novel paradigm in drug-delivery technologies. Read more: Zhan, Ying, Austin Fergusson, Lacey R. McNally, Richey M. Davis, and Bahareh Behkam. "Robust and Repeatable Biofabrication of Bacteria-Mediated Drug Delivery Systems: Effect of Conjugation Chemistry, Assembly Process Parameters, and Nanoparticle Size." Authorea Preprints (2021). https://www.authorea.com/doi/full/10.22541/au.163100509.93917936

“Abstract: Bacteria-mediated drug delivery systems comprising nanotherapeutics conjugated onto bacteria synergistically augment the efficacy of both therapeutic modalities in cancer therapy. Nanocarriers preserve therapeutics' bioavailability and reduce systemic toxicity, while bacteria selectively colonize the cancerous tissue, impart intrinsic and immune-mediated antitumor effects, and propel nanotherapeutics interstitially. The optimal bacteria-nanoparticle (NP) conjugates would carry the maximal NP load with minimal motility speed hindrance for effective interstitial distribution. Furthermore, a well-defined and repeatable NP attachment density distribution is crucial to determining these biohybrid systems' efficacious dosage and robust performance. Herein, we utilized our Nanoscale Bacteria-Enabled Autonomous Delivery System (NanoBEADS) platform to investigate the effects of assembly process parameters of mixing method, volume, and duration on NP attachment density and repeatability. We also evaluated the effect of linkage chemistry and NP size on NP attachment density, viability, growth rate, and motility of NanoBEADS. We show that the linkage chemistry impacts NP attachment density while the self-assembly process parameters affect the repeatability and, to a lesser extent, attachment density. Lastly, the attachment density affects NanoBEADS' growth rate and motility in an NP size-dependent manner. These findings will contribute to the development of scalable and repeatable bacteria-nanoparticle biohybrids for applications in drug delivery and beyond.”

PEG-PLGA from PolySciTech used in development of Boron Neutron capture therapy to treat prostate cancer

Wednesday, September 15, 2021, 2:51 PM ET

One therapy for cancer is to apply targeted radiation treatment to remove the tumor that route. To do this a sensitizer or comparable compound is loaded into a targeted system designed to specifically accumulate in the tumor site. Then the area is affected by a relatively inert force (such as low-energy neutrons) to induce a radioactive response. Recently, researchers at UCSF purchased PEG-PLGA (cat# AK037) and PLGA-PEG-COOH (cat# AI078) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with boron for delivery to prostate cancers. This enables treatment of the cancer by exposing the area to neutrons which then cause the boron to emit alpha radiation in a localized manner. This research holds promise to improve therapeutic options against difficult cancers in the future. Read more: Dhrona, Suchi. "Development of PSMA Targeted Polymer Nanoparticles to Treat Prostate Cancer By Boron Neutron Capture Therapy Directed Against PSMA." PhD diss., UCSF, 2021. https://escholarship.org/content/qt6c6292zv/qt6c6292zv.pdf

“Prostate-specific membrane antigen (PSMA) is a cell surface enzyme highly over expressed in prostate cancer cells that can be employed as a target for prostate cancer imaging and drug delivery. Boron Neutron Capture Therapy (BNCT) is an emerging noninvasive therapeutic modality for treating locally invasive malignant tumors by selective delivery of high boron content to the tumour and then subjecting the tumour to epithermal neutron beam radiation. In this study, we develop carborane encapsulated amphiphilic polymer nanoparticles by conjugating urea based PSMA inhibitors (ACUPA) and 89Zr chelating deferoxamine B (DFB) ligand and have investigated their efficacy to deliver enhanced boron payload to PSMA positive prostate cancer cells with simultaneous positron emission tomography (PET) imaging . Three different carborane encapsulated PLGA-b-PEG nanoparticles (NPs) were formulated with and without the PSMA targeting ligand, out of which two selected formulations; DFB(25)ACUPA(75) NPs and DFB(25) NPs radiolabelled with 89Zr were administered to mice bearing dual PSMA(+) PC3-Pip and PSMA(-) PC3-Flu xenografts. PET imaging and biodistribution studies were performed to demonstrate the in vivo uptake in mice. The NPs showed 2-fold higher uptake in PSMA(+) PC3-Pip tumors to that of PSMA(-) PC3-Flu tumors with a very high tumor/blood ratio of 20. However, no significant influence of the ACUPA ligands were observed. Additionally, the NPs demonstrated fast release of carborane with low delivery of boron to tumors in vivo. Although the in vivo afficacy of those NPs remain limited, a significant progress towards the synthesis, characterization and initial biological evaluation of the polymer nanoparticles is proposed in this report and the results presented could guide the future design of amphiphilic polymer NPs for theranostic applications.”

PEG-PLGA from PolySciTech used in development of curcumin-based therapy for ocular cancer treatment

Thursday, September 2, 2021, 9:04 AM ET

Curcumin is a powerful anti-oxidant compound which has properties that prevent tumor metastasis and motion. Although it is present in turmeric, simply eating turmeric (or turmeric powder/prepared foods) will not provide patients with any therapeutically meaningful quantity of curcumin as this compound has very bad water solubility and does not cross over the intestinal tract well. That being said, curcumin provided in a carrier formulation as an injectable or otherwise deliverable compound can aid in cancer treatment. Recently, researchers at University of Rhode Island used PEG-PLGA (AK026) from PolySciTech (www.polyscitech.com) to produce curcumin-loaded nanoparticles. They embedded these in a thermosensitive gel and tested the system for use against uveal melanoma. This treatment holds promise to improve therapies against cancer. Read more: Xie, Lingxiao, Weizhou Yue, Khaled Ibrahim, and Jie Shen. "A Long-Acting Curcumin Nanoparticle/In Situ Hydrogel Composite for the Treatment of Uveal Melanoma." Pharmaceutics 13, no. 9 (2021): 1335. https://www.mdpi.com/1243808

“Uveal melanoma (UM) is the most common primary intraocular tumor in adults with high mortality. In order to improve prognosis and survival of UM patients, it is critical to inhibit tumor progression and metastasis as early as possible after the initial presentation/diagnosis of the disease. Sustained local delivery of antitumor therapeutics in the posterior region can potentially achieve long-term UM inhibition, improve target therapeutic delivery to the posterior segments, as well as reduce injection frequency and hence improved patient compliance. To address the highly unmet medical need in UM therapy, a bioinspired in situ gelling hydrogel system composed of naturally occurring biopolymers collagen and hyaluronic acid was developed in the present research. Curcumin with anti-cancer progression, anti-metastasis effects, and good ocular safety was chosen as the model therapeutic. The developed in situ gelling delivery system gelled at 37 °C within two minutes and demonstrated excellent biocompatibility and slow degradation. The curcumin-loaded nanoparticle/hydrogel composite was able to sustain release payload for up to four weeks. The optimized nanoparticle/hydrogel composite showed effective inhibition of human UM cell proliferation. This novel nanoparticle/in situ hydrogel composite demonstrated a great potential for the treatment of the rare and devastating intraocular cancer. Keywords: in situ hydrogel; nanoparticle/hydrogel composite; sustained delivery; curcumin; uveal melanoma”

PEG-PLGA and PLGA from PolySciTech used in research on nanoparticle fate within the brain

Tuesday, August 31, 2021, 10:13 AM ET

Nanoparticle motion within the brain is a complicated process which is driven by the various chemical factors involved with cellular recognition and disposition towards the particles as well as the particle tendency to aggregate or ability to cross membranes. Recently, researchers from University of Washington used PEG-PLGA (AK106) and PLGA (AP059) to create a series of nanoparticles with varying surfactant-related exteriors. They then fluorescently stained these polymers and carefully tracked their motion through brain tissue to determine their motility and fate. This research holds promise to improve future nanoparticle derived therapies against brain diseases. Read more: Joseph, Andrea, Georges Motchoffo Simo, Torahito Gao, Norah Alhindi, Nuo Xu, Daniel J. Graham, Lara J. Gamble, and Elizabeth Nance. "Surfactants influence polymer nanoparticle fate within the brain." Biomaterials (2021): 121086. https://www.sciencedirect.com/science/article/pii/S0142961221004427

“Abstract: Drug delivery to the brain is limited by poor penetration of pharmaceutical agents across the blood-brain barrier (BBB), within the brain parenchyma, and into specific cells of interest. Nanotechnology can overcome these barriers, but its ability to do so is dependent on nanoparticle physicochemical properties including surface chemistry. Surface chemistry can be determined by a number of factors, including by the presence of stabilizing surfactant molecules introduced during the formulation process. Nanoparticles coated with poloxamer 188 (F68), poloxamer 407 (F127), and polysorbate 80 (P80) have demonstrated uptake in BBB endothelial cells and enhanced accumulation within the brain. However, the impact of surfactants on nanoparticle fate, and specifically on brain extracellular diffusion or intracellular targeting, must be better understood to design nanotherapeutics to efficiently overcome drug delivery barriers in the brain. Here, we evaluated the effect of the biocompatible and commonly used surfactants cholic acid (CHA), F68, F127, P80, and poly(vinyl alcohol) (PVA) on poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticle transport to and within the brain. The inclusion of these surfactant molecules decreases diffusive ability through brain tissue, reflecting the surfactant's role in encouraging cellular interaction at short length and time scales. After in vivo administration, PLGA-PEG/P80 nanoparticles demonstrated enhanced penetration across the BBB and subsequent internalization within neurons and microglia. Surfactants incorporated into the formulation of PLGA-PEG nanoparticles therefore represent an important design parameter for controlling nanoparticle fate within the brain.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.26886391639709 seconds)


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