John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

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


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mPEG-PLA from PolySciTech used by Yale University in development of a novel blood-circulation assay method

Tuesday, April 18, 2017, 10:41 AM ET

A fundamental difficulty with medicinal applications to humans is that the circulatory systems of most living organisms are designed specifically to screen out any perceived toxins or ‘non-self’ components. Typically, the kidneys and the liver work together along with macrophages (white blood cells) to remove any chemicals or particulates from the bloodstream. Although this system provides protection to the human body from toxic ingestion, it creates great difficulty for applying medicines as it greatly reduces the blood circulation time of medicinal molecules. For general medicinal applications, the loss of drug from the bloodstream is calculated as the circulation half-life and dosing schedules are calculated to match. One method to improve blood-circulation is to encapsulate the drug molecule inside of PEG-PLA so-called ‘stealth’ nanoparticles. For these particles, the PEG external coating prevents attacks by macrophages while the size alone reduces uptake and clearance by kidneys or liver. These particles enhance the blood circulation time of medicines, but a key question is by exactly how much is the blood circulation time enhanced and what is the new circulation half-life. This question critical for practical applications as it would define the dosing schedule of the encapsulated drug as it must be dosed often enough to maintain effect but not too often so as to potentially have toxic side-effects. Recently, researchers at Yale University utilized mPEG-PLA from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AK054) to generate stealth-nanoparticles as test substrates for their novel fluorescence microscopy-based technique for determining half-life of particles using as little as 2 uL of blood. This research holds promise for rapid and routine determination of half-life using very small samples of blood. Read more: Tietjen, Gregory T., Jenna DiRito, Jordan S. Pober, and W. Mark Saltzman. "Quantitative microscopy-based measurements of circulating nanoparticle concentration using microliter blood volumes." Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300643

“Abstract: Nanoparticles (NPs) are potential drug delivery vehicles for treatment of a broad range of diseases. Intravenous (IV) administration, the most common form of delivery, is relatively non-invasive and provides (in theory) access throughout the circulatory system. However, in practice, many IV injected NPs are quickly eliminated by specialized phagocytes in the liver and spleen. Consequently, new materials have been developed with the capacity to significantly extend the circulating half-life of IV administered NPs. Unfortunately, current procedures for measuring circulation half-lives are often expensive, time consuming, and can require large blood volumes that are not compatible with mouse models of disease. Here we describe a simple and reliable procedure for measuring circulation half-life utilizing quantitative microscopy. This method requires only 2 μL of blood and minimal sample preparation, yet provides robust quantitative results. Graphical Abstract: Quantitative microscopy can be used to measure circulating concentrations of nanoparticles with as little as 2 μL of blood. However, when using such small volumes, the path length within and between samples can vary significantly as the high viscosity of blood can yield differences in think layer thickness as the blood spreads following application of a coverslip. This yields variability in the measured mean fluorescence intensity. Addition of a reference nanoparticle of a different color can correct the mean fluorescence intensity variance. Thus, quantitative microscopy can serve as a robust method for measuring nanoparticle half-life using μL volumes of blood. NP formulation: NP were prepared by a standard nanoprecipitation procedure. PLA–PEG (PolyVivo AK054) was dissolved at an initial concentration of 100 mg/mL in DMSO and then diluted to the desired concentration for NP formulation (typically ~55 mg/mL for the ~165 nm NPs used in this study) along with addition of either DiI or DiO dye also dissolved in DMSO. NPs were loaded with DiI or DiO dye at a final wt dye/wt polymer ratio of 0.5%. The dye/polymer solution in DMSO was added drop wise to vigorously stirring sterile diH2O in batches of 200 μL polymer/dye solution added to 1.3 mL of diH2O with identical repetitions performed to generate a full NP batch. NP were subsequently filtered through a 1.2 μm cellulose acetate membrane (GE Healthcare Life Sciences - Whatman) filter to remove any free dye or polymer aggregates and then pooled. Typically, 8 small batches of ~11 mg polymer each were combined for a total pooled batch size of ~88 mg initial polymer weight. The pooled NP solutions were then transferred to a 12 mL volume 10,000 MWCO dialysis cassettes (Thermo Scientific - Slide-A-Lyzer) and dialyzed against 2× exchanges of ~2.2 L of diH2O at room temperature to remove excess DMSO. Following dialysis NPs were aliquoted and snap frozen in liquid N2. One aliquot from each NP batch was lyophilized in a pre-weighed tube in order to determine the NP concentration. Standard NP concentration was typically ~5 mg/mL. NP batches were diluted to ~0.1 mg/mL and analyzed via dynamic light scattering (DLS) to confirm NP size and homogeneity.”

PhD Research Thesis from The University of Milan utilizes PLGA from PolySciTech as radical chain transfer agent

Wednesday, April 12, 2017, 3:49 PM ET

Sometimes research holds surprising results. Radical chain transfer is a process which allows for controlling the molecular weight and end-cap properties of poly(vinyl) type polymers. Conventionally, radical chain transfer agents comprise of molecules custom designed for that exact purpose, such as thiol compounds in which the sulfur atom actively participates in the free radical interaction. Conventionally, PLGA is not typically applied to free radical chain transfer however researchers at The University of Milan were able to use PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP059) in this fashion to create PLGA-g-PVP. This research holds promise for the development of novel polymer compounds for a wide array of applications. Read more: Capuano, G. "Amphiphilic, Biodegradable and Biocompatible Polymers for Industrial Applications." (2017). Universita Degli Studi Di Milano Facolta Di Scienze E Tecnologie PhD School in Industrial Chemistry XXIX Cycle PhD Student Capuano Giovanna Thesis. https://air.unimi.it/bitstream/2434/477898/2/phd_unimi_R10587.pdf

“The aim of this PhD work was to establish the synthetic procedures for new families of biocompatible and biodegradable and/or bioeliminable biomaterials that can be differently processed to obtain nanoparticles, core-shell nanof ibres and hydrogel slabs or conduits, respectively. Depending on composition, size and morphology, these biomaterials may be intended for applications as drug delivery systems and/or tissue regeneration. Specifically, the research project has been developed along two main lines: Synthesis of poly(lactic-glycolic acid)-g-poly(1-vinylpyrrolidin-2-one) (PLGA-g-PVP) copolymers whose architecture consisted of a long PLGA backbone with oligomeric PVP pendants. These were obtained by the radical polymerisation of 1-vinylpyrrolidin-2-one in molten PLGA 50:50, acting as chain transfer agent. Synthesis of a new classes of poly(saccharide)-poly(aminoamine)s 3D-network intended as scaffolds for the regeneration of liver. (Synthesis of PLGA-g-PVP): PLGA (2.012 g, PolyVivo AP059) and VP (0.203 g, 1.83 mol) were added to dichloromethane (30 mL) in a two-necked 100 mL flask equipped with a stir bar. The resultant solution was purged 5 min with nitrogen and AIBN (2.1 mg, 0.013 mmol) was added. Dichloromethane was then eliminated at room temperature and 0.2 tor. After three nitrogen-vacuum cycles, the reaction mixture was heated to 100 °C, maintained at this temperature under nitrogen for 2.5 h, cooled to room temperature and dissolved in dichloromethane (100 mL). The solution was poured drop-wise in diethyl ether (1 L) under vigorous stirring and the resultant slurry stirred for further 2 h. The precipitated product was finally retrieved by filtration, washed with fresh ether (200 mL) and dried under vacuum.”

Poly(lactide) from PolySciTech used as part of bone-tissue engineering development work in recent patent application

Monday, April 10, 2017, 10:55 AM ET

Tissue engineering is an exciting field of research in which a cell scaffold is implanted to heal missing tissue. Normal human cells require a surface to adhere too and grow along. In the human body, this ‘surface’ is a group of cellular excretions, which give biochemical and mechanical (structural) support for the cells, referred to as the ‘extra cellular matrix’ (ECM). Without the ECM, cells cannot grow into the tissue. For this, and other reasons, damaged tissues will sometimes never regrow fully (e.g. amputations, defects, voids, etc.) The goal of tissue engineering is to find a way to replace the extra cellular matrix with a synthetic structure so that the surrounding cells can grow into the void area and replace it with new tissue. Recently, researchers at Pennsylvania State University published a patent in which PLLA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP047) was used as a control for bone-tissue replacement. This material, along with the experimental polymer, was processed into a porous structure by a method known as salt-leaching (see picture, Fig. 4B, for example). The examples of this patent provide excellent data regarding methodologies and use of this polymer in this application. Read more: Yang, Jian. "Methods of Promoting Bone Growth and Healing." U.S. Patent 20170080125, issued March 23, 2017. http://www.freepatentsonline.com/y2017/0080125.html

“Abstract: In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method described herein comprises disposing a graft or scaffold in a bone growth site. The graft or scaffold comprises (a) a polymer network formed from the reaction product of (i) citric acid, a citrate or an ester of citric acid with (ii) a polyol. The graft or scaffold further comprises (b) a particulate inorganic material dispersed in the polymer network.”

PLGA from PolySciTech used for development of NIR fluorescent dye delivery carrier to make tumors detectable through skin as a diagnostic aid

Friday, March 31, 2017, 5:28 PM ET

Near-infrared (NIR) is a frequency of light just outside of the range of human vision which can be seen through human flesh. The delivery of NIR fluorophores to cancer cells and other diseased tissues can provide for the opportunity to render cancer detectable through the skin by NIR fluorescent techniques. Recently, researchers at Wroclaw University (Poland) used PLGA from PolySciTech (PolyVivo AP062) to stabilize NIR active NaYF4:Er3+,Yb3 nanoparticles in a double emulsion along with nonionic surfactants. This research holds promise for allowing for improved cancer diagnostics by making tumors visible through the skin. Read more: Bazylińska, Urszula, and Dominika Wawrzyńczyk. "Encapsulation of TOPO stabilized NaYF 4: Er 3+, Yb 3+ nanoparticles in biocompatible nanocarriers: synthesis, optical properties and colloidal stability." Colloids and Surfaces A: Physicochemical and Engineering Aspects (2017). http://www.sciencedirect.com/science/article/pii/S092777571730300X

“Abstract: The emulsification process leading to up-converting NaYF4:Er3+,Yb3+ NPs encapsulation, was performed using a modified water/oil/water double emulsion evaporation method, where poly(lactic-co-glycolic acid) was used as biocompatible polymer. Span 80 and Cremophor A25 were applied as non-ionic surfactants and dichloromethane as oily phase. The use of trioctylphosphine oxide ligands for the synthesis of up-converting NaYF4:Er3+,Yb3+ NPs allowed to obtain spherical particles with sizes below 10 nm, what further facilitated the efficient encapsulation process. Those newly designed nanosystems were subjected to analysis of their morphology, colloidal stability and optical properties by: dynamic light scattering, ζ-potential, atomic force microscopy, transmission electron microscopy and measuring the up-conversion emission spectra of free and loaded NaYF4:Er3+,Yb3+ NPs. The encapsulated NaYF4:Er3+,Yb3+ NPs showed increased colloidal stability for a long period of 60 days of storage in different conditions. Simultaneously, the encapsulation process did not significantly influenced their optical properties and strong visible emission could be observed upon nearinfrared excitation. Highlights: NaYF4:Er,Yb NPs 5 nm in size were synthesized with TOPO used as a stabilizing ligands. The modified double emulsion evaporation method was successful in the up-converting NPs encapsulation. PLGA, Span 80 and Cremophor A25 act as the obtained nanosystems stabilizers. The encapsulation process retain the optical properties of NaYF4:Er3+,Yb3+ NPs. The obtained nanocarriers have potential applications as theranostic agents.”

mPEG-PCL from PolySciTech utilized in development of Chrysin-nanoparticle based therapy for lung-cancer

Tuesday, March 28, 2017, 4:59 PM ET

Lung cancer is among the leading causes of cancer-related death worldwide. Chrysin, a natural active flavone, acts to enhance the chemotherapeutic effectiveness of other chemoagents (cisplatin, docetaxel, etc.) against lung cancer. Chrysin’s usability, however, is limited by its very poor water solubility and low bioavailability. Recently, researchers at Duksung Women’s University (Korea) utilized mPEG-PCL from PolySciTech (www.polyscitech.com) (PolyVivo #: AK001) to formulate chrysin-loaded nanoparticles which were found to delay tumor progression in a mouse model. This research holds promised for improved lung-cancer therapy. Read more: Kim, Kyoung Mee, Hyun Kyung Lim, Sang Hee Shim, and Joohee Jung. "Improved chemotherapeutic efficacy of injectable chrysin encapsulated by copolymer nanoparticles." International Journal of Nanomedicine 12 (2017): 1917. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352247/

“Abstract: Chrysin is a flavone that is found in several plants and in honeycomb and possesses various biological activities. However, its low solubility means it has poor bioavailability, which must be resolved to enable its pharmaceutical applications. In the present study, chrysin was incorporated into methoxy poly(ethylene glycol)-β-polycaprolactone nanoparticles (chrysin-NPs) using the oil-in-water technique in order to overcome problems associated with chrysin. The properties of chrysin-NPs were analyzed, and their anticancer effects were investigated in vitro and in vivo. Chrysin-NPs were 77 nm sized (as determined by dynamic laser light scattering) and showed a monodisperse distribution. The zeta potential of chrysin-NPs was −2.22 mV, and they were spherically shaped by cryo-transmission electron microscopy (cryo-TEM). The loading efficiency of chrysin-NPs was 46.96%. Chrysin-NPs retained the cytotoxicity of chrysin in A549 cells. The therapeutic efficacies of chrysin-NPs were compared with those of chrysin in an A549-derived xenograft mouse model. Chrysin-NPs were intravenously injected at a 10 times lower dosage than chrysin 3 times per week (q2d×3/week). However, free chrysin was orally administrated 5 times per week (q1d×5/week). Chrysin-NP-treated group showed significant tumor growth delay, which was similar to that of chrysin-treated group, despite the considerably lower total dosage. These results suggest that the injectable chrysin-NPs enhance therapeutic efficacy in vivo and offer a beneficial formulation for chemotherapy. Keywords: chrysin, nanoparticle, chemotherapeutic efficacy, non-small-cell lung cancer, in vivo model. Nanoparticle preparation method: Chrysin (Sigma-Aldrich, St Louis, MO, USA) was incorporated into copolymer NPs using an oil-in-water technique (Figure 1). mPEG–β-polycaprolactone copolymer (mPEG-PCL, 50 mg; 2,000:5,200 Da; PolySciTech, West Lafayette, IN, USA) and 5 mg of chrysin were dissolved in a dichloromethane (Duksan reagent, Gyeonggi-do, Korea) and methanol mixture (Duksan reagent; v/v, 1.5:1). This solution (2.5 mL) was added to a 1% aqueous polyvinyl alcohol solution (6 mL) and was emulsified by sonification for 1 min. The solvent was removed by evaporation under stirring to produce NPs. To remove polyvinyl alcohol and surplus free chrysin, the supernatant was collected after centrifugation (14,000 rpm) twice at room temperature for 1 h.”


Monday, March 27, 2017, 9:49 AM ET

PolySciTech: Keeping scientists and engineers fashionably dressed since 2013. (www.polyscitech.com, free t-shirt with select orders)

PLGA from PolySciTech used in optimizing 3D printing techniques for tissue engineering

Wednesday, March 22, 2017, 4:32 PM ET

A relatively recent and powerful tool for both manufacturing and research has been developed in 3D printing. Despite it’s advantages, 3D printing is restricted based on the polymeric material’s melt and processing properties. Recently, researchers working jointly at University of Maryland, Cornell University, and Rice University screened through a series of PLGA materials in order to define the optimal printing procedures for each. The utilized a series of PLGA’s from PolySciTech (www.polyscitech.com) (PolyVivo AP039, AP137, AP076, and AP024) and optimized their printing configurations for bone-tissue engineering. This research holds promise for the capability to print biocompatible, biodegradable parts for tissue engineering and other applications. Read more at: Guo, Ting, Timothy Holzberg, Casey Lim, Feng Gao, Ankit Gargava, Jordan Trachtenberg, Antonios Mikos, and John Fisher. "3D printing PLGA: a quantitative examination of the effects of polymer composition and printing parameters on print resolution." Biofabrication (2017). http://iopscience.iop.org/article/10.1088/1758-5090/aa6370/meta

“Abstract: In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meets patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography (microCT) was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.”

PLGA-PEG-COOH from PolySciTech used in development of ultra-sound triggered breast cancer theranostic nanoparticles

Friday, March 17, 2017, 5:02 PM ET

One of the goals within controlled delivery is to provide for targeted medicinal delivery in which the medicine is guided to the site that it is needed in by natural processes. More specifically, in cancer, there is a need to delivery nanoparticles to the tumor site for both therapy (medicinal delivery) as well as diagnosis (contrast agent delivery) Recently, researchers at Chongqing Medical University (China) used PolySciTech (www.polyscitech.com) product PLGA-PEG-COOH (PolyVivo AI056) and conjugated on Herceptin (antibody which conjugates to breast cancer tumors) to target it towards breast cancer cells. They formulated these with both contrast agents and chemotherapeutic paclitaxel. This research holds promise for improved breast-cancer therapy. Read more: Song, Weixiang, Yindeng Luo, Yajing Zhao, Xinjie Liu, Jiannong Zhao, Jie Luo, Qunxia Zhang, Haitao Ran, Zhigang Wang, and Dajing Guo. "Magnetic nanobubbles with potential for targeted drug delivery and trimodal imaging in breast cancer: an in vitro study." Nanomedicine 0 (2017). http://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0027

“Aim: The aim of this study was to improve tumor-targeted therapy for breast cancer by designing magnetic nanobubbles with the potential for targeted drug delivery and multimodal imaging. Materials & methods: Herceptin-decorated and ultrasmall superparamagnetic iron oxide (USPIO)/paclitaxel (PTX)-embedded nanobubbles (PTX-USPIO-HER-NBs) were manufactured by combining a modified double-emulsion evaporation process with carbodiimide technique. PTX-USPIO-HER-NBs were examined for characterization, specific cell-targeting ability and multimodal imaging. Results: PTX-USPIO-HER-NBs exhibited excellent entrapment efficiency of Herceptin/PTX/USPIO and showed greater cytotoxic effects than other delivery platforms. Low-frequency ultrasound triggered accelerated PTX release. Moreover, the magnetic nanobubbles were able to enhance ultrasound, magnetic resonance and photoacoustics trimodal imaging. Conclusion: These results suggest that PTX-USPIO-HER-NBs have potential as a multimodal contrast agent and as a system for ultrasound-triggered drug release in breast cancer.”

PolySciTech mPEG-PLGA and PLGA-Rhodamine products used in development of advanced chemoradiotherapy delivery system

Wednesday, March 15, 2017, 4:58 PM ET

Chemoradiotherapy is a cancer therapy technique in which a sensitizer molecule is administered to a patient prior to administration of a dose of radiation. Typically, such a technique is made difficult as the sensitizer molecule can affect both tumor tissue and normal tissue, causing more damage from radiation. However, with the application of localized-delivery to the tumor, this technique holds great potential for cancer therapy by allowing specific and selective destruction of tumor tissue at a relatively lower dose of radiation. Recently, researchers at the University of North Carolina Chapel Hill utilized PolySciTech (www.polyscitech.com)mPEG-PLGA’s (PolyVivo AK010, AK023) and fluorescently-tagged polymer PLGA-rhodamine B (PolyVivo AV011) for development of an advanced nanoparticle delivery system for Wortmannin (DNA-PK inhibitor) or novel KU60019 (ATM inhibitor) molecules. Both of these molecules act to increase local radiation damage to tumors by preventing DNA repair. The researchers found that smaller particles were more effective at avoiding hepatic clearance but medium sized particles showed more efficacy for sensitization. This research holds promise for enhanced cancer treatment techniques. Read more: Caster, Joseph M., K. Yu Stephanie, Artish N. Patel, Nicole J. Newman, Zachary J. Lee, Samuel B. Warner, Kyle T. Wagner et al. "Effect of particle size on the biodistribution, toxicity, and efficacy of drug-loaded polymeric nanoparticles in chemoradiotherapy." Nanomedicine: Nanotechnology, Biology and Medicine (2017). http://www.sciencedirect.com/science/article/pii/S1549963417300448

“Abstract: Nanoparticle (NP) therapeutics can improve the therapeutic index of chemoradiotherapy (CRT). However, the effect of NP physical properties, such particle size, on CRT is unknown. To address this, we examined the effects of NP size on biodistribution, efficacy and toxicity in CRT. PEG-PLGA NPs (50, 100, 150 nm mean diameters) encapsulating wotrmannin (wtmn) or KU50019 were formulated. These NP formulations were potent radiosensitizers in vitro in HT29, SW480, and lovo rectal cancer lines. In vivo, the smallest particles avoided hepatic and splenic accumulation while more homogeneously penetrating tumor xenografts than larger particles. However, smaller particles were no more effective in vivo. Instead, there was a trend towards enhanced efficacy with medium sized NPs. The smallest KU60019 particles caused more small bowel toxicity than larger particles. Our results showed that particle size significantly affects nanotherapeutics' biodistrubtion and toxicity but does not support the conclusion that smaller particles are better for this clinical application. Graphical Abstract: Sub50 nm drug-loaded NPs avoid hepatic clearance and more homogeneously distribute within tumors. However, they are no more efficacious and are associated with more small bowel toxicity than larger particles. Keywords: Nanoparticle; Chemoradiotherapy; Nanoparticle radiosensitization; KU60019; Wortmannin”

Parkinson’s disease treatment developed using mPEG-PLGA block copolymer for neuroprotective agent delivery

Wednesday, March 15, 2017, 8:49 AM ET

Parkinson’s disease is a chronic, neural-degenerative which affects motor control and other operations of the nervous system eventually leading to death. Schisantherin A is a recently discovered neuroprotective agent which acts to inhibit damage to neural cells and can be used to slow the progression of Parkinson’s disease (https://www.ncbi.nlm.nih.gov/pubmed/25770828). It has severe limitations, however, as it is poorly soluble in water and quickly cleared from the blood-stream. Schisantherin A , like many neurological medicines, also faces the severe impediment of the blood-brain-barrier. This barrier which exists between circulating blood and brain tissue is intended to protect the brain from any toxic components that may be in the blood but also serves the unintentional purpose of preventing uptake of medicinal components into the brain tissue. Recently, researchers at University of North Carolina at Chapel Hill and University of Macau utilized mPEG-PLGA to generate small-sized nanoparticles containing Schisantherin A. They found these nanoparticles to improve serum circulation longevity and uptake across the blood-brain-barrier. This research holds promise for enhanced therapy against this fatal disease. Similar block copolymers can be purchased from PolySciTech division of Akina, Inc. (www.polyscitech.com). Read more about this exciting research here: Chen, Tongkai, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, and Ying Zheng. "Small-Sized mPEG–PLGA Nanoparticles of Schisantherin A with Sustained Release for Enhanced Brain Uptake and Anti-Parkinsonian Activity." ACS Applied Materials & Interfaces (2017). http://pubs.acs.org/doi/abs/10.1021/acsami.7b01171

“Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson’s disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)-block-poly(d,l)-lactic-co-glycolic acid (mPEG–PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of 91% and drug loading of 28%. The in vitro release of the SA-NPs lasted for 48 h with a sustained-release pattern. Using the Madin–Darby canine kidney (MDCK) cell model, the results showed that first intact nanoparticles carrying hydrophobic dyes were internalized into cells, then the dyes were slowly released within the cells, and last both nanoparticles and free dyes were externalized to the basolateral side of the cell monolayer. Fluorescence resonance energy transfer (FRET) imaging in zebrafish suggested that nanoparticles were gradually dissociated in vivo with time, and nanoparticles maintained intact in the intestine and brain at 2 h post-treatment. When SA-NPs were orally administrated to rats, much higher Cmax and AUC0-t were observed in the plasma than those of the SA suspension. Furthermore, brain delivery of SA was much more effective with SA-NPs than with SA suspension. In addition, the SA-NPs exerted strong neuroprotective effects in zebrafish and cell culture models of PD. The protective effect was partially mediated by the activation of the protein kinase B (Akt)/glycogen synthase kinase-3β (Gsk3β) pathway. In summary, this study provides evidence that small-sized mPEG–PLGA nanoparticles may improve cross-barrier transportation, oral bioavailability, brain uptake, and bioactivity of this Biopharmaceutics Classification System (BCS) Class II compound, SA. Keywords: brain delivery; cellular uptake; fluorescence resonance energy transfer (FRET); mPEG−PLGA nanoparticles; oral bioavailability; Schisantherin A”

PLGA-PEG-Maleimide from PolySciTech used in development of macular degeneration treatment

Monday, March 6, 2017, 4:44 PM ET

One of the causes of ocular damage which can lead to blindness is choroidal neovascularization, effectively the over-growth of new blood vessels in the back of the eye. This condition is involved in the development of age-related macular degeneration which can lead to blindness. Recently, researchers at Yantai University (China) utilized Mal-PEG-PLGA (PolyVivo AI020) from PolySciTech (www.polyscitech.com) to develop RGD and TAT peptide modified nanoparticles to deliver therapeutics to ocular tissues as part of treatment of macular degeneration. This research holds promise to provide treatment for a disease which causes blindness. Read more: Chu, Yongchao, Ning Chen, Huajun Yu, Hongjie Mu, Bin He, Hongchen Hua, Aiping Wang, and Kaoxiang Sun. "Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles." International Journal of Nanomedicine 12 (2017): 1353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325139/

“Abstract: A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. Keywords: nanoparticles, ocular drug delivery, choroidal neovascularization, RGD, cell-penetrating peptides. Method for iRGD Conjugation: Briefly, Mal–PEG–PLGA was dissolved in acetone and the organic solvent then evaporated, dispersing the solute evenly on the flask wall. The flask was replenished with 0.01 M phosphate-buffered saline (PBS, pH 7.4) and left overnight to react with iRGD. The iRGD was conjugated to Mal–PEG–PLGA (at 4°C, at a 1:1 molar ratio of peptide to Mal–PEG–PLGA).”

PLGA from PolySciTech investigated for use as adjuvant in Streptococcus vaccine development

Monday, March 6, 2017, 4:43 PM ET

Group A Strep is highly virulent and can be deadly without proper treatment. One means to reduce Strep infections is to apply nanoparticles presenting certain portions of the bacteria’s M-protein marker to elicit an immune response against Strep. Recently, researchers at The University of Queensland and Griffith University (Australia) utilized PolySciTech (www.polyscitech.com) PLGA (PolyVivo AP041) to develop a nanoparticle vaccine against strep. They utilized PLGA as well as poly(lysine) and dextran to make these nanoparticles and found a substantially higher immune response against the PLGA likely due to its negative charge. This research holds promise for the development of an effective vaccine against Strep. Read more: Marasini, Nirmal, Ashwini Kumar Giddam, Michael R. Batzloff, Michael F. Good, Mariusz Skwarczynski, and Istvan Toth. "Poly-L-lysine-coated nanoparticles are ineffective in inducing mucosal immunity against group a streptococcus." (2017). http://www.hoajonline.com/journals/pdf/2052-9341-5-1.pdf

“Abstract Background: Group A Streptococcus (GAS) can cause a range of maladies, from simple throat infections to lethal complication, such as rheumatic heart disease. The M-protein, a bacterial cell surface protein, is the major virulence factor of GAS. Several attempts have been made over the past few decades to develop vaccines against GAS that employed peptides derived from the M-protein. One such approach used lipopeptides or lipid core peptide (LCP) systems that incorporated a B-cell epitope derived from the conserved region of the M-protein. Methods: In the present study, we prepared different biodegradable polymer [dextran, poly-(lactic- coglycolic-acid) (PLGA), and poly-L-lysine] nanoparticles (NPs)-based delivery systems for a lipopeptide vaccine candidate (LCP-1).The NPs were characterized by their size, charge, morphology, antigen-presenting cells (APCs) uptake and subsequent APCs maturations efficacy, followed by in vivo nasal immunization in mice. Results: All produced NPs ranged in size from 100-205 nm, and their charge varied depending upon the nature of polymer. A high APCs uptake efficacy for dextran and poly-L-lysine NPswere observed, compared to PLGA NPs. Despite the high uptake by APCs, dextran and poly-L-lysine NPs failed to improve APCs maturation that resulted in low antibody titres. In contrast, while LCP-1 encapsulated into PLGA showed low APCs uptake, it induced significant maturation of DCs and higher antibody titres compared to other NPs. Conclusions: Positively-charged poly-L-lysine NPs were non-immunogenic, while negatively charged PLGA NPs induced similar responses to antigens adjuvanted with cholera toxin B (CTB). Keywords: Mucosal delivery, lipopeptides, nanoparticles, nasal, vaccine, PLGA, Poly-L-lysine”

End-of-Grant promo, Gamma sterilization, and Carbonate buffer technical notes

Thursday, March 2, 2017, 11:18 AM ET

The PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers and other research supplies. March ends the fiscal quarter for several institutions and grants which is why we are having a special end-of-quarter promotion. Orders between $100-250 receive a free drink-coozy, orders $250-500 receive a free string-backpack and orders >$500 receive a free PolySciTech T-shirt. As manager of Akina, I receive technical questions and sometimes I receive the same ones quite often. Often, I receive questions about gamma sterilizing our products. Our experience has been, however, that it is common for ionizing radiation techniques such as this to cause some degradation and cross-linking of polyesters which can change their mechanical properties (tend to become brittle) and their solubility properties (may become insoluble). This is similar to literature reports for the effects of radiation on polymers (http://link.springer.com/article/10.1023/A:1016256903322, http://www.sciencedirect.com/science/article/pii/0032386183901982). One way to reduce this damage is to perform the radiation dosing in an inert gas (argon or nitrogen). We've found this reduces some of the reactions which require the participation of atmospheric oxygen, humidity, or other gasses. Alternatively, depending on your application, it may be worthwhile to investigate alternate sterilization techniques such as ethylene oxide exposure. Another issue which has recently come up is the dissolution of thermogelling polymers (PLGA-PEG-PLGA, PLCL-PEG-PLCL) in specific buffers. Thermogel polymers of this category represent a balance between the hydrophilic attractions of the PEG block to water molecules and the hydrophobic attractions of the polyester blocks to each other. Species dissolved in the water which interfere with the water attractions can affect the performance of these thermogels. Although these work well in water, phosphate and several other buffers, they do not work well in carbonate buffers. Likely, this is due to the effects of carbonate species on water’s hydrogen bonding properties (http://pubs.acs.org/doi/abs/10.1021/jp809069g). Poor solubility of these thermogels has been reported in carbonate buffers and avoidance of carbonate buffer is suggested for these materials.

Thermogel PLGA-PEG-PLGA from PolySciTech used in development of minimally invasive liver-cancer microwave ablation therapy

Monday, February 27, 2017, 5:05 PM ET

Recently, researchers have developed improvements in the localization and effectiveness of Microwave Ablation therapy by combining PolySciTech Division of Akina, Inc. (www.polyscitech.com) thermogelling product (PLGA-PEG-PLGA PolyVivo, Cat# AK088) with non-radioactive Cesium chloride to create an injectable thermal accelerant. This research holds promise for improved ablation treatment of liver cancer. Read more: Park, William Keun Chan, Aaron Wilhelm Palmer Maxwell, Victoria Elizabeth Frank, Michael Patrick Primmer, Scott Andrew Collins, Grayson Luderman Baird, and Damian Edward Dupuy. "Evaluation of A Novel Thermal Accelerant For Augmentation Of Microwave Energy During Image-guided Tumor Ablation." Theranostics, in print (2017). http://www.thno.org/v07p1026.pdf

“The primary challenge in thermal ablation of liver tumors (e.g. hepatocellular carcinoma and hepatic colorectal cancer) is the relatively high recurrence rate (~30%) for which incomplete ablation at the periphery of the tumor is the most common reason. In an attempt to overcome this, we have developed a novel thermal accelerant (TA) agent capable of augmenting microwave energy from a distance normally unattainable by a single microwave ablation antenna. This cesium-based block co-polymer compound transforms from a liquid to a gel at body temperature and is intrinsically visible by computed tomography. Using an agarose phantom model, herein we demonstrate that both the rate and magnitude of temperature increase during microwave ablation were significantly greater in the presence of TA when compared with controls. These results suggest robust augmentation of microwave energy, and may translate into larger ablation zone volumes within biologic tissues. Further work using in vivo techniques is necessary to confirm these findings. Key words: Image-guided thermal ablation, microwave ablation, thermal accelerant, augmentation of microwave energy, non-radioactive cesium chloride, block-co-polymer, PLGA-PEG-PLGA, dipole moment, complex dielectric permittivity, dielectric constant, loss factor.”

New whitepaper on thermogelling PLCL-PEG-PLCL aqueous storage stability as a ready-to-go solution

Wednesday, February 22, 2017, 11:51 AM ET

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers. One class of these is thermogelling polymers which can dissolve in cold water and then form into a solid gel once the water is warmed above the LCST. In some situations, one may want to dissolve the polymer in an aqeous solution and then store it in this ready-to-go condition for some time prior to use. As these polymers are hydrolysable, there is a finite span of time that this gel solution can be stored. Recently, accelerated degradation testing was performed using PLCL-PEG-PLCL PolyVivo AK109. The PLCL blocks provide for slower degradation as compared with PLGA blocks and this study was designed to see how long these thermogels can be store. You can see more on this here (http://akinainc.com/pdf/AK109%20storage%20stability.pdf)

mPEG-PLA from PolySciTech used as part of SPION-methicillin loaded nanoparticle development for eradication of drug-resistant bacterial biofilms

Tuesday, February 21, 2017, 10:34 AM ET

There is increasing prevalence of bacterial resistance towards antibiotics due to genetic as well as structural changes. Notably, certain types of bacteria tend to form into tight biofilms which are surrounded by a protective matrix that reduces antibiotic infiltration. These biofilms can be up to 1000 times more resistant towards conventional antibiotics than loose bacteria and account for up to 60% of all infectious diseases in the western world. Recently, researchers at Northeastern University utilized mPEG-PLA (PolyVivo cat# AK021) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to co-encapsulate iron-oxide particles and methicillin inside polymeric nanoparticles. They discovered that these nanoparticles, under a magnetic field, were able to penetrate deep into staph-bacteria biofilms and kill the bacteria, while having no toxicity towards mammalian cells. This research holds promise for providing advanced treatment options of drug-resistant bacteria and infections at medical implant surfaces. Read more: Geilich, Benjamin M., Ilia Gelfat, Srinivas Sridhar, Anne L. van de Ven, and Thomas J. Webster. "Superparamagnetic iron oxide-encapsulating polymersome nanocarriers for biofilm eradication." Biomaterials 119 (2017): 78-85. http://www.sciencedirect.com/science/article/pii/S0142961216307086

“Abstract: The rising prevalence and severity of antibiotic-resistant biofilm infections poses an alarming threat to public health worldwide. Here, biocompatible multi-compartment nanocarriers were synthesized to contain both hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) and the hydrophilic antibiotic methicillin for the treatment of medical device-associated infections. SPION co-encapsulation was found to confer unique properties, enhancing both nanocarrier relaxivity and magneticity compared to individual SPIONs. These iron oxide-encapsulating polymersomes (IOPs) penetrated 20 μm thick Staphylococcus epidermidis biofilms with high efficiency following the application of an external magnetic field. Three-dimensional laser scanning confocal microscopy revealed differential bacteria death as a function of drug and SPION loading. Complete eradication of all bacteria throughout the biofilm thickness was achieved using an optimized IOP formulation containing 40 μg/mL SPION and 20 μg/mL of methicillin. Importantly, this formulation was selectively toxic towards methicillin-resistant biofilm cells but not towards mammalian cells. These novel iron oxide-encapsulating polymersomes demonstrate that it is possible to overcome antibiotic-resistant biofilms by controlling the positioning of nanocarriers containing two or more therapeutics. Keywords: Biofilm; Polymersome; SPION; Staphylococcus epidermidis; Antibiotic-resistance; Nanomedicine”

Akanocure Press Release

Tuesday, February 7, 2017, 3:18 PM ET

You can obtain commercially available Akanocure products at https://akinainc.com/polyscitech/products/akanocure/index.php read more in a a recent press release regarding Akanocure is available here http://www.purdue.edu/newsroom/releases/2017/Q1/purdue-affiliated-pharmaceutical-company-launches-product-to-produce-rare-disease-fighting-compounds.html

Amine-endcap PLGA from PolySciTech used in development of heart-attack treatment

Tuesday, February 7, 2017, 12:51 PM ET

Heart attack, or myocardial infarction, is the leading cause of death worldwide. One of the causes of tissue damage which occurs during a heart attack is excess calcium influx that occurs once blood-flow is reestablished (reperfusion). This calcium influx leads to cell death and massive tissue damage to the heart muscles rendering them inoperable which can be lethal for the patient. Recently, researchers working jointly at University of Iowa and Mahidol University (Thailand), utilized PLGA-NH2 from PolySciTech division of Akina, Inc. (www.polyscitech.com) (PolyVivo AI063) as a component in developing a targeted nanoparticle preparation which delivered an CaMKII inhibitor peptide to prevent heart-cell death during reperfusion. This research holds promise for the development of a medicine which can be used to prevent tissue damage during a heart-attack potentially aiding in life-saving therapy. Read more here: Wongrakpanich, Amaraporn, Angie S. Morris, Sean M. Geary, A. Joiner Mei-ling, and Aliasger K. Salem. "Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury." International Journal of Pharmaceutics (2017). http://www.sciencedirect.com/science/article/pii/S0378517317300704

“Abstract: An excess of calcium (Ca2+) influx into mitochondria during mitochondrial re-energization is one of the causes of myocardial cell death during ischemic/reperfusion injury. This overload of Ca2+ triggers the mitochondrial permeability transition pore (mPTP) opening which leads to programmed cell death. During the ischemic/reperfusion stage, the activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) enzyme is responsible for Ca2+ influx. To reduce CaMKII-related cell death, sub-micron particles composed of poly(lactic-co-glycolic acid) (PLGA), loaded with a CaMKII inhibitor peptide were fabricated. The CaMKII inhibitor peptide-loaded (CIP) particles were coated with a mitochondria targeting moiety, triphenylphosphonium cation (TPP), which allowed the particles to accumulate and release the peptide inside mitochondria to inhibit CaMKII activity. The fluorescently labeled TPP-CIP were taken up by mitochondria and successfully reduced ROS caused by Isoprenaline (ISO) in a differentiated rat cardiomyocyte-like cell line. When cells were treated with TPP-CIP prior ISO exposure, they maintained mitochondrial membrane potential. The TPP-CIP protected cells from ISO-induced ROS production and decreased mitochondrial membrane potential. Thus, TPP-CIP have the potential to be used in protection against ischemia/reperfusion injury.”

PLGA from PolySciTech used as part of optimized doxorubicin nanoparticle study

Tuesday, January 31, 2017, 2:56 PM ET

Nanoparticles references formulations which are submicron in size. A great deal of expertise goes into making nanoparticles with precise properties and this is an exciting field of research for a wide variety of treatments. Recently, researchers utilized PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) for formulation optimization of doxorubicin loaded particles. This research holds promised for improved chemotherapy strategies. Read more: Shaikh, Muhammad Vaseem, Manika Kala, and Manish Nivsarkar. "Formulation and optimization of doxorubicin loaded polymeric nanoparticles using Box-Behnken design: ex-vivo stability and in-vitro activity." European Journal of Pharmaceutical Sciences (2017). http://www.sciencedirect.com/science/article/pii/S0928098717300507

“Abstract: Biodegradable nanoparticles (NPs) have gained tremendous interest for targeting chemotherapeutic drugs to the tumor environment. Inspite of several advances sufficient encapsulation along with the controlled release and desired size range have remained as considerable challenges. Hence, the present study examines the formulation optimization of doxorubicin loaded PLGA NPs (DOX-PLGA-NPs), prepared by single emulsion method for cancer targeting. Critical process parameters (CPP) were selected by initial screening. Later, Box-Behnken design (BBD) was used for analyzing the effect of the selected CPP on critical quality attributes (CQA) and to generate a design space. The optimized formulation was stabilized by lyophilization and was used for in-vitro drug release and in-vitro activity on A549 cell line. Moreover, colloidal stability of the NPs in the biological milieu was assessed. Amount of PLGA and PVA, oil:water ratio and sonication time were the selected independent factors for BBD. The statistical data showed that a quadratic model was fitted to the data obtained. Additionally, the lack of fit values for the models was not significant. The delivery system showed sustained release behavior over a period of 120 h and was governed by Fickian diffusion. The multipoint analysis at 24, 48 and 72 h showed gradual reduction in IC50 value of DOX-PLGA-NPs (p < 0.05, Fig. 9). DOX-PLGA-NPs were found to be stable in the biological fluids indicating their in-vivo applicability. In conclusion, optimization of the DOX-PLGA-NPs by BBD yielded in a promising drug carrier for doxorubicin that could provide a novel treatment modality for cancer.”

Oral chemotherapeutic delivery system developed using PCL from PolySciTech

Monday, January 30, 2017, 5:16 PM ET

Paclitaxel is a widely applicable anticancer agent which prevents cancer cells from dividing and proliferating. Currently, the only administration route for paclitaxel is by intravenous injection. For chronic applications, this can be a very invasive procedure, such as surgical placement of a PICC line in the vein of the arm or port-a-cath directly into the entrance of the heart. Clearly, an oral delivery system would be preferred in terms of patience comfort as well as management of costs and potential complications associated with catheters. By itself, Paclitaxel has very poor uptake when administered orally. However, researchers have utilized PCL (PolyVivo AP129) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) and conjugated it to chitosan to form a biocompatible micelle system which significantly enhances paclitaxel absorption. This research holds promise for less-invasive and more sustainable delivery of paclitaxel to patients. Read more: Almeida, Andreia, Daniella Silva, Virginia Gonçalves, and Bruno Sarmento. "Synthesis and characterization of chitosan-grafted-polycaprolactone micelles for modulate intestinal paclitaxel delivery." Drug Delivery and Translational Research (2017): 1-11. http://link.springer.com/article/10.1007/s13346-017-0357-8

“Abstract: In this work, self-assembled amphiphilic micelles based on chitosan (CS) and polycaprolactone (PCL) were produced and used as carriers of paclitaxel (PTX) to improve its intestinal pharmacokinetic profile. Chitosan-grafted-polycaprolactone (CS-g-PCL) was synthesized through a carbodiimide reaction by amidation and confirmed by Fourier transform infrared spectroscopy (FTIR), hydrogen nuclear magnetic resonance analysis (1H NMR), and contact angle evaluation. Micelles were produced by solvent evaporation method, and the critical micelle concentration was investigated by conductimetry. The obtained micelles were of 408-nm mean particle size, narrow size distribution (polydispersity index of 0.335) and presented positive surface charge around 30 mV. The morphology of micelles assessed by transmission electron microscopy (TEM) revealed round and smooth surface, in agreement with dynamic light scattering measurements. The association efficiency determined by high-performance liquid chromatography (HPLC) was as high as 82%. The in vitro cytotoxicity of the unloaded and PTX-loaded micelles was tested against Caco-2 and HT29-MTX intestinal epithelial cells, resulting in the absence of cell toxicity for all formulations. Moreover, the permeability of PTX-loaded micelles in Caco-2 monolayer and Caco-2/HT29-MTX co-culture model was determined. Results showed that the permeability of PTX was higher in Caco-2/HT29-MTX co-culture model compared with Caco-2 monolayer due to the mucoadhesive character of micelles, acting as a platform to deliver PTX at the sites of absorption. Therefore, it can be concluded that the PTX-loaded CS-g-PCL micelles, employed for the first time as PTX carriers, may be a potential drug carrier for the intestinal delivery of hydrophobic drugs, particularly anticancer agents. Keywords: Chitosan, Polycaprolactone, Paclitaxel, Micelles, Drug delivery”

Stem-cell tissue scaffold for spinal-repair constructed using polymers from PolySciTech

Tuesday, January 24, 2017, 3:53 PM ET

An exciting application of biodegradable polymer technology is the regeneration of new tissue using an appropriate scaffold seeded with mesenchymal stem cells. Recently, researchers utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo cat# AP045) as part of a scaffold system to support the regrowth of spinal cord tissue using stem cells. This research holds promise for potentially repairing spinal breaks as a treatment for paralysis. Read more: Ropper, Alexander E., Devang K. Thakor, InBo Han, Dou Yu, Xiang Zeng, Jamie E. Anderson, Zaid Aljuboori et al. "Defining recovery neurobiology of injured spinal cord by synthetic matrix-assisted hMSC implantation." Proceedings of the National Academy of Sciences (2017): 201616340. http://www.pnas.org/content/early/2017/01/12/1616340114.short

“Abstract: Mesenchymal stromal stem cells (MSCs) isolated from adult tissues offer tangible potential for regenerative medicine, given their feasibility for autologous transplantation. MSC research shows encouraging results in experimental stroke, amyotrophic lateral sclerosis, and neurotrauma models. However, further translational progress has been hampered by poor MSC graft survival, jeopardizing cellular and molecular bases for neural repair in vivo. We have devised an adult human bone marrow MSC (hMSC) delivery formula by investigating molecular events involving hMSCs incorporated in a uniquely designed poly(lactic-co-glycolic) acid scaffold, a clinically safe polymer, following inflammatory exposures in a dorsal root ganglion organotypic coculture system. Also, in rat T9–T10 hemisection spinal cord injury (SCI), we demonstrated that the tailored scaffolding maintained hMSC stemness, engraftment, and led to robust motosensory improvement, neuropathic pain and tissue damage mitigation, and myelin preservation. The scaffolded nontransdifferentiated hMSCs exerted multimodal effects of neurotrophism, angiogenesis, neurogenesis, antiautoimmunity, and antiinflammation. Hindlimb locomotion was restored by reestablished integrity of submidbrain circuits of serotonergic reticulospinal innervation at lumbar levels, the propriospinal projection network, neuromuscular junction, and central pattern generator, providing a platform for investigating molecular events underlying the repair impact of nondifferentiated hMSCs. Our approach enabled investigation of recovery neurobiology components for injured adult mammalian spinal cord that are different from those involved in normal neural function. The uncovered neural circuits and their molecular and cellular targets offer a biological underpinning for development of clinical rehabilitation therapies to treat disabilities and complications of SCI. Keywords: spinal cord injury recovery, neurobiology, mesenchymal stromal stem cell, PLGA, locomotion.”.

mPEG-PLLA from PolySciTech used for synthesis of photodynamic chemotherapy agent.

Friday, January 20, 2017, 2:08 PM ET

Photodynamic therapy is a novel cancer treatment option which utilizes special agents, referred to as photosensitizers. These reagents are inactive and non-toxic under typical conditions but can be activated by certain wavelengths of light to kill cancerous cells. The benefit of such a therapy, over conventional chemotherapy, is that the location of action can be controlled by selectively illuminating the tumor region. PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide variety of block copolymers which work well for forming micelle or nanoparticle formulations for medicinal delivery. Recently, mPEG-PLLA (PolyVivo AK004) was utilized by researchers at Wroclaw University as a precursor to synthesize zinc(II) phthalocyanine conjugate for photodynamic therapy. This research holds promise for safe and effective cancer therapy with lower side-effects. Read more: Lamch, Łukasz, Marta Tsirigotis-Maniecka, Julita Kulbacka, and Kazimiera A. Wilka. "Synthesis of new zinc (II) phthalocyanine conjugates with block copolymers for cancer therapy." Organic Chemistry part ii (2017): 433-445. http://www.arkat-usa.org/get-file/58826/

“Abstract: Synthetic routes towards new conjugates of hydrophilic zinc(II) phthalocyanine (ZnPc) with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (Pluronic P123) and poly(L-lactide) (PLLA), are described. The main semiproduct ZnPc was obtained by heating 4-nitrophthalimide with urea and zinc chloride, followed by the reduction step. Steglich esterification was used to synthesize two ZnPc-conjugated block copolymers, further utilized in fabrication of polymeric micelles (PMs) - functionalized with the zinc(II) phthalocyanine-type moiety. Biological evaluation of the PMs indicated an acceptable biocompatibility level in accord with requirements in the field of nanotheranostics and nanomedicine. Keywords: ZnPc-conjugated block copolymers; cyclotetramerization; Steglich esterification; fluorescent polymeric micelles; diagnostic marker; in vitro biological evaluation”

Uses for Akanocure Stereotetrad Lactones 5b: Full Lactone Reductions

Friday, January 20, 2017, 2:06 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of (+)-neopeltolide fragments, a chemotherapeutic agent. This research holds promise for improved availability of chemotherapeutic agents. Read more: Mineeva, I. "New approach to the synthesis of macrocyclic core of cytotoxic lactone (+)-neopeltolide. Synthesis of CC segment basing on cyclopropanol intermediates." Russian Journal of Organic Chemistry 51, no. 8 (2015). http://link.springer.com/article/10.1134/S1070428015080023

“A new retrosynthetic procedure was developed for the synthesis of the macrocyclic core of a cytotoxic lactone (+)-neopeltolide utilizing cyclopropanol intermediates. The synthesis was suggested and carried out of the C7–C16 segment of (+)-neopeltolide to obtain (4S,6S)-6-[(2S)-2-hydroxypentyl]-4-methyltetrahydro-2H-pyran-2-one. The possibility was demonstrated of a formal synthesis based on the obtained product of the potential antitumor pharmaceutical (+)-neopeltolide.”

Uses for Akanocure Stereotetrad Lactones 5a: Full Lactone Reductions

Friday, January 20, 2017, 2:06 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential usage is the full reduction of the lactone. This reaction has been utilized in the past to provide for synthesis of salinomycin, a powerful antibiotic agent which has proven itself effective against problematic bacterial such as MRSA. This research holds promise for improved antibiotics production. Read more: Yadav, J. S., Vinay K. Singh, and P. Srihari. "Formation of Substituted Tetrahydropyrans through Oxetane Ring Opening: Application to the Synthesis of C1–C17 Fragment of Salinomycin." Organic letters 16, no. 3 (2014): 836-839. http://pubs.acs.org/doi/abs/10.1021/ol403604u?journalCode=orlef7&quickLinkVolume=16&quickLinkPage=836&selectedTab=citation&volume=16

“The stereoselective synthesis of C1–C17 fragment of salinomycin is achieved. The strategy employs a desymmetrization approach and utilizes an intramolecular oxetane opening reaction with O-nucleophile to result in the tetrahydropyran skeleton as the key step.”

Uses for Akanocure Stereotetrad Lactones 4: lactone openings with sulfur nucleophiles

Friday, January 20, 2017, 2:05 PM ET

One of PolySciTech’s latest product offerings is Akanocure stereotetrad lactones (https://akinainc.com/polyscitech/products/akanocure/index.php) for use as synthetic precursors. There are many potential reactions for these lactones which can result in a wide array of useful molecules. In this series of postings, we will highlight potential uses of these materials. One potential reaction is the ring-opening of the lactone using sulfur (thiol) nucleophiles. Recently, this reaction has been applied to the synthesis of peloruside A, a potent chemotherapeutic agent. This research holds promise for improved availability of advanced chemotherapeutic agents. Read more: Raghavan, Sadagopan, and V. Vinoth Kumar. "A stereoselective synthesis of the C9–C19 subunit of (+)-peloruside A." Organic & biomolecular chemistry 11, no. 17 (2013): 2847-2858. http://pubs.rsc.org/en/content/articlelanding/2013/ob/c3ob27508f#!divAbstract

“Abstract: The stereoselective synthesis of a C9–C19 fragment of the potent antitumor agent peloruside A is disclosed. The C11 stereogenic centre was created by a vinylogous Mukaiyama aldol reaction following Carreira's protocol, with excellent stereocontrol. The C13 stereogenic centre was introduced by a substrate controlled reduction. The C15 stereocentre was fashioned using Noyori's asymmetric transfer hydrogenation while the Z-trisubstituted double bond was formed by a regioselective hydrostannation of an alkyne followed by methylation of the resultant vinyl stannane using Lipshutz's protocol. The C18 chiral centre was introduced by a chemoenzymatic route.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/.

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