PLGA from PolySciTech used in development of veterinary peptide/nanoparticle-based vaccine against bovine paratuberculosis

In addition to human medical applications, there are also a wide range of veterinary applications for biodegradable polymers. Paratuberculosis is a costly disease of the bovine small intestine which occurs with high prevalence in US dairy herds. Currently available vaccines do not provide complete protection from infection due to poor immune activation. Attenuated virus vaccines against Paratuberculosis can only be used in sheep as they cause cross-reactivity in cattle. For this reason, dairy farmers have relatively little recourse against this disease to protect their herds. Recently, researchers working jointly at Washington State University, the US department of agriculture, and Alexandria University (Egypt) used PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP054) to create peptide-based vaccine (rather than killed or attenuated-virus) loaded nanoparticles for improved effectiveness. This research holds promise to improve dairy cattle disease resistance which will ensure a more sustainable food supply. Read more: Souza, Cleverson D., John P. Bannantine, Wendy C. Brown, M. Grant Norton, William C. Davis, Julianne K. Hwang, Parissa Ziaei et al. "A nano particle vector comprised of poly lactic‐co‐glycolic acid and monophosphoryl lipid A and recombinant Mycobacterium avium subsp paratuberculosis peptides stimulate a pro‐immune profile in bovine macrophages." Journal of Applied Microbiology (2017). http://onlinelibrary.wiley.com/doi/10.1111/jam.13491/full

“Abstract: Aims: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide based vaccines for Paratuberculosis in cattle. Methods and Results: Peptides derived from Mycobacterium avium subsp paratuberculosis (Map), and the proinflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (D, L-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function. PLGA/MPLA NPs, with and without Map antigens, are efficiently phagocytized by macrophages with no evidence of toxicity. PLGA/MPLA NP formulations did not alter the level of expression of MHC I or II molecules. Expression of TNFα and IL12p40 was increased in Map loaded NPs. T cell proliferation studies using a model peptide from Anaplasma marginale demonstrated that a CD4 T cell recall response could be elicited with macrophages pulsed with the peptide encapsulated in the PLGA/MPLA NP. Conclusions: These findings indicate PLGA/MPLA NPs can be used as a vehicle for delivery and testing of candidate peptide based vaccines. Keywords: PLGA ; monophosphoryl lipid A; Mycobacterium avium subsp. paratuberculosis; Anaplasma marginale ; peptide vaccine”

Biodegradable polyesters (PLGA, PLA, PCL) from PolySciTech investigated for controlling Mg-based cardiovascular stent degradation

One treatment for cardiovascular disease is balloon angioplasty, in which a stent is emplaced at the site of arterial blockage in the heart. Initial work with bare-metal stents had reasonably successful results in keeping the artery open by providing structural support but, over time, the tissue of the vessel would grow back over the stent and into the interior portion of it reclosing the artery by a process known as restenosis. A variety of strategies have been applied to solving this issue. One strategy is to utilize a temporary, biodegradable stent comprised primarily of magnesium, which slowly corrodes back into biocompatible magnesium ions leaving no foreign surface for the arterial cells to grow over. However, the speed of Mg breakdown, on its own, is too rapid for stent application. Recently, researchers working at University of California at Riverside and Norco College utilized PLGA, PLLA, and PCL from PolySciTech (www.polyscitech.com) PLLA (No. AP007), PLGA (90:10) (No. AP049), PLGA (50:50) (No. AP089), and PCL (No. AP009) to develop a series of biodegradable coatings to cover over magnesium-type stents. These coatings were used to delay Mg degradation and to improve the stent-surface interaction with arterial cells. This research holds promise for improved cardiovascular treatment by using biodegradable stents which do not suffer from late-stage restenosis. Read more: Jiang, Wensen, Qiaomu Tian, Tiffany Vuong, Matthew Shashaty, Chris Gopez, Tian Sanders, and Huinan Liu. "Comparison Study on Four Biodegradable Polymer Coatings for Controlling Magnesium Degradation and Human Endothelial Cell Adhesion and Spreading." ACS Biomaterials Science & Engineering (2017). http://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.7b00215

“Magnesium (Mg)-based bioresorbable cardiovascular scaffold (BCS) is a promising alternative to conventional permanent cardiovascular stents, but it faces the challenges of rapid degradation and poor endothelium recovery after device degradation. To address these challenges, we investigated poly(l-lactic acid) (PLLA), poly(lactic-co-glycolic acid) (PLGA) (90:10), PLGA (50:50), and polycaprolactone (PCL) coatings on Mg, respectively, and evaluated their surface and biological properties. Intact polymer coatings with complete coverage on Mg substrate were achieved. The biological performance of the materials was evaluated by culturing with human umbilical vein endothelial cells (HUVECs) in vitro using the direct culture method. The pH of the culture media and Mg2+ and Ca2+ ion concentrations in the media were measured after culture to characterize the degradation rate of the materials in vitro. The results showed that the PLGA (50:50) coating improved the adhesion and spreading of HUVECs the most among the four polymer coatings. Moreover, we found three possible factors that promoted HUVECs directly attached on the surface of PLGA (50:50)-coated Mg: (1) the higher concentration of Mg2+ ions released into culture media with a concentration range of 9–15 mM; (2) the lower Ca2+ ion concentration in culture media at 1.3–1.6 mM; and (3) the favorable surface conditions of PLGA (50:50), when compared with the other sample groups. This in vitro study provided the first evidence that the PLGA (50:50) is a promising coating material for Mg-based biodegradable metals toward potential cardiovascular or neurovascular applications. Keywords: bioresorbable cardiovascular scaffold; bioresorbable magnesium implants; human umbilical vein endothelial cells; in vitro direct culture method; polymer coatings”

PLGA-PEG-amine from PolySciTech used to generate brain-penetrating nanoparticles for treatment of neural diseases

A significant problem in treating disease which affect the brain is that getting medicine into the brain tissue is very difficult. This is due to the ‘blood-brain-barrier’ which prevents medicines in the bloodstream from crossing over into the brain tissue. This is a unique feature of the brain, as other organs (kidneys, liver, lungs, etc.) readily absorb medicines from the blood stream. A simple method to overcome this barrier is to simply dose the medicine so high that even if a small portion of the drug crosses into the brain it is effective. However, this strategy does not work with medicines that have side-effects at high doses. Another method of dealing with this problem is to generate medicine-loaded nanoparticles which are specifically modified in such a way as to allow them to penetrate across the blood-brain barrier so they can deliver medicine into the brain for treatment of neural diseases. Recently, researchers working jointly at University of Southern Denmark (Denmark) and Instituto de Investigacao e Inovacao em Saude (Portugal) utilized PLGA-PEG-NH2 from PolySciTech (www.polyscitech.com) (PolyVivo AI058) to generate transferrin decorated nanoparticles for blood-brain-barrier penetration. This research holds promise for improved delivery of medicine to brain tissue for improved treatment of cancer or neural disease such as alzeheimers. Read more: Gomes, Maria Joao, Patrick J. Kennedy, Susana Martins, and Bruno Sarmento. "Delivery of siRNA silencing P-gp in peptide-functionalized nanoparticles causes efflux modulation at the blood–brain barrier." Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0023

“Aim: Explore the use of transferrin-receptor peptide-functionalized nanoparticles (NPs) targeting blood–brain barrier (BBB) as siRNA carriers to silence P-glycoprotein (P-gp). Materials & methods: Permeability experiments were assessed through a developed BBB cell-based model; P-gp mRNA expression was evaluated in vitro; rhodamine 123 permeability was assessed after cell monolayer treatment with siRNA NPs. Results: Beyond their ability to improve siRNA permeability through the BBB by twofold, 96-h post-transfection, functionalized polymeric NPs successfully reduced P-gp mRNA expression up to 52%, compared with nonfunctionalized systems. Subsequently, the permeability of rhodamine 123 through the human BBB model increased up to 27%. Conclusion: Developed BBB-targeted NPs induced P-gp downregulation and consequent increase on P-gp substrate permeability, revealing their ability to modulate drug efflux at the BBB.”

PLGA from PolySciTech used as part of development of pH responsive nanoparticles for cancer treatment

One of the fundamental problems with treatment of cancer is that the disease itself is still “part” of the human body. Cancer is simply a portion of the tissue and cells which are growing/proliferating at the wrong rate or in a manner which is damaging other tissues. For most diseases caused by an external pathogen, designing a medicinal treatment is simply a matter of finding an agent which affects the pathogen and not the patient. For example, the antibiotic penicillin prevents synthesis of cell-walls, which are key components of bacteria but not found in human cells. For this reason, penicillin can be easily administered to patients at high systemic doses with minimal concern for side effects. Unfortunately, for cancer, the situation is not so simple. Most agents which act to kill or prevent growth of cancer cells also have similar action on healthy cells, due to the fact both that the disease and the patient are of the same cell-type. For this reason, the few differences between cancer cells and normal cells that do exist are ideal targets to improve the action of therapeutics against cancer while maintaining minimal activity against normal cells. One difference between normal tissues and cancer is that, due differences in tumor metabolism, the tumor tissues become acidic with pH ~6.5-7 (typical cellular pH is 7.4). This has led to rumors that acidity causes the tumor to grow and that cancer can be prevented, or even cured, simply by consuming pH basic (or so-called “alkaline”) foods. If this was truly the case, then cancer could be cured by simply eating Rolaids or TUMS, which is not the case. It is the growing cancer generates the acidic environment, not the other way around. This pH variability is one difference between normal tissue and cancerous tissues which can be used for optimizing targeted drug strategies. Recently, researchers working jointly at Purdue University, Fudan University (China), Shenyang Pharmaceutical University (China), and Eli Lilly, utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP081) to create drug-loaded nanoparticles. These were surface modified to render them pH sensitive for preferential release at low pH. Although they worked well during in-vitro testing, there were problems with components of blood interacting with the coating and altering it preventing the pH effect from being fully utilized during in-vivo research. This is an important aspect of real science is that often, during development, there are setbacks to overcome which are discovered over the course of the research. This research holds promise for development of improved chemotherapeutics. Read more: Han, Ning, Jun Xu, Liang Pang, Hyesun Hyun, Jinho Park, and Yoon Yeo. "Development of surface-variable polymeric nanoparticles for drug delivery to tumors." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00050

“Abstract: To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments. Keywords: acid anhydrides; drug delivery; pH sensitive; PLGA nanoparticles; TAT peptide”

PLGA from PolySciTech used as rapamycin eluting coating on magnesium alloy stents for restenosis prevention as part of heart-disease research

A popular treatment for cardiac blockage is angioplasty. Under this treatment, a thin catheter is run up to the affection portion of the heart and then a balloon is expanded near the tip to remove the blockage. A drawback to this technique is that, over time, the affected blood vessel re-narrows unless something is left in place, such as a stent. Over a longer period of time, the tissues of the blood vessel will regrow over the stent and re-block the vessel by a process called restenosis. A wide variety of technologies have been applied to dealing with this issue so as to provide a long-term and effective angioplasty treatment for treating coronary artery diseases which can lead to heart-attacks if the vessel.  Recently, Researchers working jointly at Purdue University, Shanghai Jiao Tong University (China), and Microport Endovascular Co. utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP122) to generate a drug-loaded coating on the stent which released anti-proliferative rapamycin to prevent restenosis. They tested this coating both on conventional stainless steel surfaces as well as novel magnesium alloys. They analyzed these samples for drug release, polymer degradation, cellular response, and other parameters. They found drug release was accelerated by the magnesium alloy underlayment and that these materials showed superior anti-proliferative capacity relative to stainless steel. This research holds promise to effectively treat coronary artery disease and prevent heart-attacks by maintaining good blood flow through the blood vessels of the heart. Read more:  Shi, Yongjuan, Jia Pei, Lei Zhang, Byung Kook Lee, Yeonhee Yun, Jian Zhang, Zhonghua Li, Song Gu, Kinam Park, and Guangyin Yuan. "Understanding the effect of magnesium degradation on drug release and anti-proliferation on smooth muscle cells for magnesium-based drug eluting stents." Corrosion Science (2017). http://www.sciencedirect.com/science/article/pii/S0010938X16314433

“Abstract: To understand the possible influence of substrate degradation on the drug-loading system of magnesium alloy-based drug-eluting stents, a rapamycin drug-loading poly(lactic-co-glycolic acid) coating was prepared on Mg-Nd-Zn-Zr stents for a systematic investigation in a phosphate buffer system. Mg degradation accelerated the drug release kinetics prominently, which was mainly attributed to H2 evolution in the diffusion-controlled phase while thereafter to PLGA erosion. Although physiochemical stability of the released rapamycin was partially deteriorated by magnesium degradation, the drug-loading system on magnesium substrates exhibited a more potent long-term inhibition on smooth muscle cell proliferation in vitro as compared to drug-loaded stainless steel. Highlights: We firstly reported that the degradation of magnesium substrate would improve the in vitro rapamycin release from drug-loading PLGA/RAPA system on a Mg-Nd-Zn-Zr alloy. We quantitatively analyzed the factors enhancing the in vitro drug release kinetics from Mg-based drug-eluting system, distinguishing that it was mainly caused by H2 evolution, while pH only played a trivial role. We reported for the first time that the Mg-based PLGA/RAPA drug-loading system exhibited more pronounced long-term inhibition for the proliferation of smooth muscle cells, under conditions that PLGA with low degradation rate was used as the drug carrier. Keywords Magnesium; Organic coatings; Polymer; Erosion; Interfaces; Kinetic parameters.”

PLGA from PolySciTech used for generating dopamine-Mn coated theranostic nanoparticles for use in cancer treatment

Chemotherapy is the primary means of treating cancer however the currently available regimens suffer from significant side-effects and related toxicity due to the non-specific nature of this approach which damages both tumors as well as normal tissues. Combination therapies have been developed as a means for dealing with this by providing for a more targeted approach to cancer treatment in which the tumor is affected by the medicine to a greater degree than healthy tissues. Recently, PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP040) was utilized to generate a doxorubicin loaded nanoparticle coated with dopamine and manganese. These particles serve both as magnetic resonance contrast agent and as a photothermal-triggered delivery system. This research holds promise for improved treatment of a wide array of cancers. Read more: Xi, Juqun, Lanyue Da, Changshui Yang, Rui Chen, Lizeng Gao, Lei Fan, and Jie Han. "Mn2+-coordinated PDa@ DOX/Plga nanoparticles as a smart theranostic agent for synergistic chemo-photothermal tumor therapy." International Journal of Nanomedicine 12 (2017): 3331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411169/

“Abstract: Nanoparticle drug delivery carriers, which can implement high performances of multi-functions, are of great interest, especially for improving cancer therapy. Herein, we reported a new approach to construct Mn2+-coordinated doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles as a platform for synergistic chemo-photothermal tumor therapy. DOX-loaded PLGA (DOX/PLGA) nanoparticles were first synthesized through a double emulsion-solvent evaporation method, and then modified with polydopamine (PDA) through self-polymerization of dopamine, leading to the formation of PDA@DOX/PLGA nanoparticles. Mn2+ ions were then coordinated on the surfaces of PDA@DOX/PLGA to obtain Mn2+-PDA@DOX/PLGA nanoparticles. In our system, Mn2+-PDA@DOX/PLGA nanoparticles could destroy tumors in a mouse model directly, by thermal energy deposition, and could also simulate the chemotherapy by thermal-responsive delivery of DOX to enhance tumor therapy. Furthermore, the coordination of Mn2+ could afford the high magnetic resonance (MR) imaging capability with sensitivity to temperature and pH. The results demonstrated that Mn2+-PDA@ DOX/PLGA nanoparticles had a great potential as a smart theranostic agent due to their imaging and tumor-growth-inhibition properties. Keywords: PLGA nanoparticles, polydopamine, chemo-photothermal therapy, smart theranostic agent”

Amine-endcap PLGA from PolySciTech used in the development of nanoparticle based asthma treatment

Asthma is a very common disease affecting over 300 million people across the globe and is typified by severe inflammation of respiratory passages. Recently, overexpression of a Ca2+/calmodulin-dependent protein kinase (CaMKII) has been identified as one of the pathways which leads to this inflammation in asthma patients. A peptide which acts to inhibit CaMKII has been identified however delivering high doses of this peptide specifically to the lung-tissue requires a unique delivery system. Recently, Researchers working jointly at University of Iowa, Johns Hopkins University, and Mahidol University (Thailand) utilized amine-end capped PLGA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AI063) along with chitosan to develop inhalable cationic nanoparticle to deliver this peptide to the lung-tissue. They found this particle to be effective at cell penetration and to provide for asthma treatment with minimal side-effects in a mouse model. This research holds promise for improved asthma therapy. Read more: Morris, Angie S., Sara C. Sebag, John D. Paschke, Amaraporn Wongrakpanich, Kareem Ebeid, Mark E. Anderson, Isabella M. Grumbach, and Aliasger K. Salem. "Cationic CaMKII Inhibiting Nanoparticles Prevent Allergic Asthma." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00114

“Abstract: Asthma is a common lung disease affecting over 300 million people worldwide and is associated with increased reactive oxygen species (ROS), eosinophilic airway inflammation, bronchoconstriction and mucus production. Targeting of novel therapeutic agents to the lungs of patients with asthma may improve efficacy of treatments and minimize side effects. We previously demonstrated that Ca2+/calmodulin-dependent protein kinase (CaMKII) is expressed and activated in the bronchial epithelium of asthmatic patients. CaMKII inhibition in murine models of allergic asthma reduces key disease phenotypes, providing the rationale for targeted CaMKII inhibition as a potential therapeutic approach for asthma. Herein we developed a novel cationic nanoparticle (NP)-based system for delivery of the potent and specific CaMKII inhibitor peptide, CaMKIIN, to airways. CaMKIIN-loaded NPs abrogated the severity of allergic asthma in a murine model. These findings provide the basis for development of innovative, site-specific drug delivery therapies, particularly for treatment of pulmonary diseases such as asthma. Keywords: Polylactide-co-glycolide, PLGA, Nanoparticle, Chitosan, Asthma, CaMKIIN”