Wednesday, April 18, 2018

mPEG-PLGA from PolySciTech used in development of advanced AFM-IR nanoparticle characterization techniques

The best thing about nanotechnology is that it is small. The worst thing about nanotechnology is that it is small… very small… smaller than what a standard light microscope can typically observe. Naturally, obtaining meaningful information about the structure and morphology of nanoparticles is very difficult and requires advanced equipment and analysis techniques. Recently, researchers at University of Sydney (Australia) used mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate nanorods and analyzed these using a combination of atomic force microscopy and infrared spectroscopy. These nano-analysis techniques allowed the researchers to measure the various mechanical, structural, and chemical properties of even a single nanoparticle with incredible precision and accuracy. This research holds promise to allow for improved characterization of nanoparticles which will enable better designs and synthesis in the future. Read more: Khanal, Dipesh, Bokai Zhang, Iqbal Ramzan, Curtis Marcott, Quan Li, and Wojciech Chrzanowski. "Probing Chemical and Mechanical Nanodomains in Copolymer Nanorods with Correlative Atomic Force Microscopy—Nanocorrescopy." Particle & Particle Systems Characterization (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/ppsc.201700409

“Abstract: The interplay between size, shape, mechanical properties, and surface chemistry of nanoparticles orchestrates cellular internalization, toxicity, circulation time, and biodistribution. Therefore, the safety of nanoparticles hinges on our ability to quantify nanoscale physicochemical characteristics. Current characterization tools, due to their limited resolution, are unable to map these properties correlatively at nanoscale. An innovative use of atomic force microscopybased techniques, namely nanocorrescopy, overcomes this limitation and offers multiprobe capability to map mechanical (viscous and elastic) and chemical domains of nanoparticles correlatively. The strengths of this approach are demonstrated using polymer composite nanorods: mPEGPLGA ((mPEG–methoxypoly (ethylene glycol)bpoly (lacticcoglycolic) acid). Precise distribution of PLGA (monomers of lactide and glycolide) and poly(ethylene glycol) (PEG) polymer across nanorods is identified. The hydrophobic lactide component is found predominantly at the apex, while hydrophilic glycolide and PEG assembled at the body of the nanorods and correlate with a gradient of nanomechanical properties. New knowledge of how both nanochemical domains and nanomechanical properties are distributed across the nanorod will allow elucidating the interactions of nanorods with the proteins and biomolecules in the future, which will directly influence the fate of nanorods in vivo and will guide new synthesis methods.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Friday, April 13, 2018

PEG-PLA from PolySciTech used in development of ocular-delivery system to treat inflammation

Inflammatory diseases are typified by an over-reaction of the human immune system against either some trigger or, in some-cases, without a specific trigger. Many diseases are caused by inflammation, however delivery of anti-inflammatory drugs is not always easily accomplished due to location or other disease complications. Recently, researchers at Stony Brook University and Medicon Pharmaceuticals utilized PEG-PLA (Polyvivo AK005) from PolyScitech (www.polyscitech.com) to generate anti-inflammatory nanoparticles for delivery of Phospho-sulindac to the ocular region. Read more: Robert A. Honkanen, Liqun Huang, Gang Xie, Basil Rigas “Phospho-sulindac is efficacious in an improved concanavalin a-based rabbit model of chronic dry eye disease” Translational Research (2018) https://www.sciencedirect.com/science/article/pii/S1931524418300562

“Abstract: Dry eye disease (DED), an inflammatory disease of the ocular surface, affects 15% of humans worldwide. No satisfactory treatment exists for DED partly due to the lack of informative animal models of this disease. We evaluated the anti-inflammatory phosphosulindac (PS) for the treatment of DED, using a new rabbit model of chronic DED. In this model, based on the Concanavalin A (Con A) acute DED model, we injected weekly x3 all lacrimal glands with ConA under ultrasound guidance, which prolonged DED to >3 weeks; and used concurrently four parameters of efficacy: tear break up time (TBUT), tear osmolarity, Schirmer's test, and tear lactoferrin levels, making efficacy assessment robust. Rabbits with DED (n=8-10 eyes/group) were treated topically with PS or vehicle 3x/day for 21 days. PS restored to normal TBUT, tear osmolarity and lactoferrin levels (p<0 .0001="" 1="" 6="" 8="" a="" abbreviations:="" account="" acid="" activated="" activation="" activity="" albumin="" amp="" an="" and="" animal="" anti-inflammatory="" apparent="" assay="" b="" beta="" bovine="" break="" bsa="" buffered="" but="" c-jun="" cause="" cells="" completely="" con="" concanavalin="" concentration="" cornea.="" cornea="" corneal="" cyclosporine="" ded.="" ded="" deviation="" diclofenac="" did="" disease="" dodecyl="" drug="" drugs="" dry="" e2="" effect="" effects="" efficacious="" efficacy="" electophoretic="" elisa="" emsa="" enzyme-linked="" eosin="" erk="" error="" establish="" evaluation="" extracellular="" eye="" factor="" for="" further="" gland="" glycol-block-polylactic="" growth="" h="" had="" half="" hematoxylin="" ic50="" il-1="" il-6="" il-8="" ilg="" immunoprecipitation="" immunosorbent="" improve="" in="" indicate="" inferior="" inhibitory="" interleukin="" international="" its="" iu="" jnk="" kappa-light-chain-enhancer="" ketorolac="" kinases="" lacrimal="" levels="" lifitegrast.="" likely="" list="" mapks="" matrix="" maximal="" mean="" melt="" merits="" metalloproteinase="" milliliter="" minute="" mitogen="" ml="" mmp-1="" mmp-9="" mmp="" mmps.="" mmps="" mobility="" model="" more="" much="" n-terminal="" nearly="" new="" nf-="" no="" nonsteroidal="" not="" nsaids="" nuclear="" nzw="" o:p="" ocular="" of="" on="" ophthalmic="" or="" orbital="" oslg="" osmolarity="" our="" palpebral="" pbs="" peg-pla="" per="" pge2="" phosphate="" phosphosulindac="" polyethylene="" portion="" preserved="" progstaglandin="" protein="" ps-treated="" ps="" pslg="" rabbits.="" radio="" regulated="" results="" revolutions="" ripa="" rpm="" s="" safety.="" saline="" schirmer="" sd="" sds="" sem="" serum="" shift="" showed="" side="" signal="" significantly="" slg="" sodium="" standard="" stt="" studies="" suitable="" sulphate="" superior="" suppressed="" tbut="" tear="" tears="" test.="" test="" tgf-="" than="" that="" the="" time="" tosm="" transforming="" two="" ultrasonography="" units="" up="" us="" was="" were="" white="" zealand="">

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Monday, April 9, 2018

PEG-PLGA from PolySciTech used in development of dual-drug loaded nanoparticles for cisplatin-resistant ovarian cancer treatment



Despite effective first-line therapies based on platinum-type drugs, ovarian cancer remains one of the deadliest gynecological diseases in the USA. The incidence of relapse is high, as is the development of platinum-resistant ovarian cancer lines that cannot be treated well using cisplatin. Recently, researchers at University of North Carolina at Chapel Hill, Westminster College, Peking Union Medical College and China Medical University (China) used mPEG-PLGA (PolyvivoAK029)  and PLGA ( PolyVivo AP087) from PolySciTech (www.polyscitech.com) to develop nanoparticles that deliver both wortmannin and cisplatin. They found this co-delivery system was very effective against ovarian cancer models in which the cancer was resistant to platinum-based drugs, as the wortmannin prevented the cancer from repairing its own DNA. This research holds promise for development of therapies against drug-resistant cancers. Read more: Zhang, Maofan, C. Tilden Hagan, Yuangzeng Min, Hayley Foley, Xi Tian, Feifei Yang, Yu Mi et al. "Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models." Biomaterials (2018). https://www.sciencedirect.com/science/article/pii/S0142961218302333

“Abstract: Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed. Herein, we report that NP co-delivery of cisplatin (CP) and wortmannin (Wtmn), a DNA repair inhibitor, synergistically enhances chemoradiotherapy (CRT) and reverses CP resistance in PROC. We encapsulated this regimen in FDA approved poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) NPs to reduce systemic side effects, enhance cellular CP uptake, improve Wtmn stability, and increase therapeutic efficacy. Treatment of platinum-sensitive ovarian cancer (PSOC) and PROC murine models with these dual-drug loaded NPs (DNPs) significantly reduced tumor burden versus treatment with combinations of free drugs or single-drug loaded NPs (SNPs). These results support further investigation of this NP-based, synergistic drug regimen as a means to combat PROC in the clinic. Keywords: Nanoparticle; Combination therapy; Platinum resistance; Treatment synergy; Ovarian cancer”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Mal-PEG-PLGA from PolySciTech used in development of oral-exanatide formulation for improved diabetes treatment.



The incidence of type 2 diabetes has expanded rapidly over the past several decades and is characterized by uncontrolled blood-sugar. Exanatide is a peptide based drug which acts to increase the pancreas response for insulin secretion as a means to control blood sugar. Due to the sensitivity of this peptide to degradation, as well as its poor bioavailability, it is currently only available as an injection. Recently, researchers at Yantai University and Binzhou Medical University (China) used Mal-PEG-PLGA (PolyVivo AI020) and PEG-PLGA (AK037) from PolySciTech (www.polyscitech.com) to develop a transferrin-coated exenatide delivery nanoparticle system that could be ingested and had high bioavailablity. This research holds promise for the development of improved oral diabetes treatment options. Read more: Zhang, Liping, Yanan Shi, Yina Song, Dongyu Duan, Xuemei Zhang, Kaoxiang Sun, and Youxin Li. "Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide." Journal of Drug Targeting just-accepted (2018): 1-36. https://www.tandfonline.com/doi/abs/10.1080/1061186X.2018.1455839

“Abstract: Safe and effective oral delivery of peptide is a challenge. Here, we used exenatide and zinc ions (Zn2+) to form a complex to explore a meaningful oral-targeted drug-delivery system. Polyethylene glycol-poly(lactic acid-co-glycolic acid) (PEG-PLGA) was used to prepare nanoparticles (NPs) to escape the degradation caused by gastrointestinal enzymes. Transferrin (Tf) was used as a targeting group. PEG-PLGA-NPs and Tf-modified exenatide-Zn2+-loaded NPs (Tf-PEG-PLGA-NPs) were uniformly sized spheres according to transmission electron microscopy. The results of pharmacodynamic and pharmacokinetic investigations in vivo were consistent with in vitro studies using Caco-2 cells. Tf enhanced NPs transport in cell-uptake and transmembrane-transport experiments. Our results showed that the relative bioavailability of Tf-exenatide-Zn2+-NPs was higher than that of exenatide-Zn2+-NPs. The relative bioavailability of Tf-exenatide-Zn2+-NPs versus subcutaneous injection of exenatide was 6.45%. This was a preliminary exploration of the oral administration of exenatide, that data from which can be used for future investigations. Keywords: transferrin, exenatide-Zn2+, PEG-PLGA, targeted nanoparticles, oral delivery”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

PLGA from PolySciTech used in development of ellipsoid-shaped/lipid-coated particles with controlled cell interaction



By typical manufacturing techniques, microparticles are simple, spherical, homogenous structures with little feature of interest. This is, effectively, the only configuration possible by conventional emulsion-type manufacturing techniques. There are a great deal of potential applications for developing microparticles which do not obey this simple shape. Recently, researchers at Johns Hopkins University used PLGA (PolyVivo AP087) from PolySciTech (www.polyscitech.com) to develop oblong-shaped microparticles with a carefully controlled coating of a lipid shell bearing various moieties. They investigated the interactions of these particles with cells and proteins and found that ellipsoid particles were resistant to macrophage uptake as well as had several other interesting features. This research holds promise for the development of advanced drug-delivery platforms as well as for other biomedical applications. Read more: Meyer, Randall A., Mohit P. Mathew, Elana Ben-Akiva, Joel C. Sunshine, Ron B. Shmueli, Qiuyin Ren, Kevin J. Yarema, and Jordan J. Green. "Anisotropic Biodegradable Lipid Coated Particles for Spatially Dynamic Protein Presentation." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118301880

“Abstract: There has been growing interest in the use of particles coated with lipids for applications ranging from drug delivery, gene delivery, and diagnostic imaging to immunoengineering. To date, almost all particles with lipid coatings have been spherical despite emerging evidence that non-spherical shapes can provide important advantages including reduced non-specific elimination and increased target-specific binding. We combine control of core particle geometry with control of particle surface functionality by developing anisotropic, biodegradable ellipsoidal particles with lipid coatings. We demonstrate that these lipid coated ellipsoidal particles maintain advantageous properties of lipid polymer hybrid particles, such as the ability for modular protein conjugation to the particle surface using versatile bioorthogonal ligation reactions. In addition, they exhibit biomimetic membrane fluidity and demonstrate lateral diffusive properties characteristic of natural membrane proteins. These ellipsoidal particles simultaneously provide benefits of non-spherical particles in terms of stability and resistance to non-specific phagocytosis by macrophages as well as enhanced targeted binding. These biomaterials provide a novel and flexible platform for numerous biomedical applications. Statement of Significance: The research reported here documents the ability of non-spherical polymeric particles to be coated with lipids to form anisotropic biomimetic particles. In addition, we demonstrate that these lipid-coated biodegradable polymeric particles can be conjugated to a wide variety of biological molecules in a “click-like” fashion. This is of interest due to the multiple types of cellular mimicry enabled by this biomaterial based technology. These features include mimicry of the highly anisotropic shape exhibited by cells, surface presentation of membrane bound protein mimetics, and lateral diffusivity of membrane bound substrates comparable to that of a plasma membrane. This platform is demonstrated to facilitate targeted cell binding while being resistant to non-specific cellular uptake. Such a platform could allow for investigations into how physical parameters of a particle and its surface affect the interface between biomaterials and cells, as well as provide biomimetic technology platforms for drug delivery and cellular engineering. Keywords: Lipids; Polymers; Membrane fluidity; Particle shape; Biomimetic”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Thursday, April 5, 2018

Poly(lactide) from PolySciTech used in generating light-activated shape-changing microparticles

Shape memory is an effect in which polymer chains temporarily entangle holding the material in a set shape until the polymer is heated above a specific rubber-glass transition temperature at which point the polymer chains can move and the material naturally forms back into its original shape. Recently, researchers at Johns Hopkins University purchased PLA (PolyVivo AP004) from PolySciTech (www.polyscitech.com) and used it to create a gold nanoparticle loaded microparticle which changes from elongated shapes into spherical shapes when heated gently by exposure to light. This research holds promise to create materials with tunable macrophage uptake for a variety of biomedical applications. Read more: Guo, Qiongyu, Corey J. Bishop, Randall A. Meyer, David R. Wilson, Lauren Olasov, Daphne E. Schlesinger, Patrick T. Mather, James B. Spicer, Jennifer H. Elisseeff, and Jordan J. Green. "Entanglement-Based Thermoplastic Shape Memory Polymeric Particles with Photothermal Actuation for Biomedical Applications." ACS Applied Materials & Interfaces (2018). https://pubs.acs.org/doi/abs/10.1021/acsami.8b01582

“Abstract: Triggering shape memory functionality under clinical hyperthermia temperatures could enable the control and actuation of shape memory systems in clinical practice. For this purpose, we developed light-inducible shape memory microparticles composed of a poly (D,L-lactic acid) (PDLLA) matrix encapsulating gold nanoparticles (Au@PDLLA hybrid microparticles). This shape memory polymeric system for the first time demonstrates the capability of maintaining an anisotropic shape at body temperature with triggered shape memory effect back to a spherical shape at a narrow temperature range above body temperature with a proper shape recovery speed (37 ˚C < T < 45 ˚C). We applied a modified film-stretching processing method with carefully controlled stretching temperature to enable shape memory and anisotropy in these micron-sized particles. Accordingly, we achieved purely entanglement-based shape memory response without chemical crosslinks in the miniaturized shape memory system. Furthermore, these shape memory microparticles exhibited light-induced spatiotemporal control of their shape recovery using a laser to trigger photothermal heating of doped gold nanoparticles. This shape memory system is composed of biocompatible components and exhibits spatiotemporal controllability of its properties, demonstrating potential for various biomedical applications, such as tuning macrophage phagocytosis as demonstrated in this study.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com

Tuesday, April 3, 2018

Malemide-PEG-PLGA and mPEG-PLGA from PolySciTech used in developing ligand-decorated, curcumin-loaded nanoparticles for breast-cancer treatment


There is a greater interface between herbal/traditional medicine and scientific medicine than most know about. Medicine can be derived from many natural sources (e.g. Paclitaxel derived from Pacific Yew tree) and medicinal chemists often focus on discovering new therapeutic agents derived from nature. Tumeric, and more specifically the extracted curcumin, has been of great interest lately due to curcumin’s anti-cancer properties. Simply eating tumeric spice, however, does not yield a significant anticancer effect for the majority of the body as curcumin has very poor absorption across the intestine. However, properly formulated and purified curcumin, can be a very powerful anticancer agent. It has an advantage over other chemotherapeutics in that it has minimal side-effects. Recently, researchers at Yantie University (China) used Maleimide-PEG-PLGA (PolyVivo AI020) and mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate curcumin loaded nanoparticles with Fab targeting ligands for treating breast cancer. This research holds promise for effective breast-cancer treatment with minimal chemotherapy side effects. Read more:  Duan, Dongyu, Aiping Wang, Ling Ni, Liping Zhang, Xiuju Yan, Ying Jiang, Hongjie Mu, Zimei Wu, Kaoxiang Sun, and Youxin Li. "Trastuzumab-and Fab′ fragment-modified curcumin PEG-PLGA nanoparticles: preparation and evaluation in vitro and in vivo." International Journal of Nanomedicine 13 (2018): 1831. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868600/

“Abstract: Introduction: Nanoparticles (NPs) modified with bio-ligands represent a promising strategy for active targeted drug delivery to tumour. However, many targeted ligands, such as trastuzumab (TMAB), have high molecular weight, limiting their application for targeting. In this study, we prepared Fab’ (antigen-binding fragments cut from TMAB)-modified NPs (Fab′-NPs) with curcumin (Cur) as a model drug for more effective targeting of human epidermal growth factor receptor 2 (HER2/ErbB2/Neu), which is overexpressed on breast cancer cells. Material and methods: The release kinetics was conducted by dialysis bags. The ability to kill HER2-overexpressing BT-474 cells of Fab′-Cur-NPs compared with TMAB-Cur-NPs was conducted by cytotoxicity experiments. Qualitative and quantitative cell uptake studies using coumarin-6 (fluorescent probe)-loaded NPs were performed by fluorescence microscopy and flow cytometry. Pharmacokinetics and biodistribution experiments in vivo were assessed by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Results: The release kinetics showed that both Fab′-Cur-NPs and TMAB-Cur-NPs provided continuous, slow release of curcumin for 72 h, with no significant difference. In vitro cytotoxicity experiments showed that Fab′-Cur-NPs manifested prominent ability to kill HER2-overexpressing BT-474 cells compared with TMAB-Cur-NPs. Qualitative and quantitative cell uptake studies indicated that the accumulation of Fab′-NPs was greater than that of TMAB-NPs in BT-474 (HER2+) cells; However, there was no significant difference in MDA-MB-231 (HER2−) cells. Pharmacokinetics and biodistribution experiments in vivo demonstrated that the half-life (t1/2) and area under the blood concentration-time curve (AUC0-t) of Fab′-Cur-NPs increased 5.30-fold and 1.76-fold relative to those of TMAB-Cur-NPs, respectively. Furthermore, the tumor accumulation of Fab′-Cur-NPs was higher than that of TMAB-Cur-NPs. Conclusion: Fab′ fragment has greater capacity than the intact antibody to achieve tumor targeting through NP-based delivery. Keywords: trastuzumab-modified curcumin nanoparticles, Fab′-modified curcumin nanoparticles, pharmacokinetics, biodistribution, tumour targeting, breast cancer”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific networking conference hosted by Akina, Inc. which focuses on research companies in the biotechnology, pharmaceutical, medical, and broader life-science fields. See more at BPCRconference.com