Monthly Archives: January 2014

Poly(aspartic acid) (Polyvivo AO05) investigated for SiRNA delivery

Recent publication investigates the use of PolyVivo AO05 (Poly(aspartic acid) along with chondroitin sulfate and poly(glutamic acid) for generating anionic polymer coated liposome/siRNA complexes to deliver SiRNA by IV injection.  Hattori, Yoshiyuki, Ayako Nakamura, Shohei Arai, Mayu Nishigaki, Hiroyuki Ohkura, Kumi Kawano, Yoshie Maitani, and Etsuo Yonemochi. “In vivo siRNA delivery system for targeting to the liver by poly-l-glutamic acid-coated lipoplex.”Results in Pharma Sciences (2014). http://www.sciencedirect.com/science/article/pii/S2211286314000025

“ABSTRACT: In this study, we developed anionic polymer-coated liposome/siRNA complexes (lipoplexes) with chondroitin sulfate C (CS), poly-l-glutamic acid (PGA) and poly-aspartic acid (PAA) for siRNA delivery by intravenous injection, and evaluated the biodistribution and gene silencing effect in mice. The sizes of CS-, PGA- and PAA-coated lipoplexes were about 200 nm and their ζ-potentials were negative. CS-, PGA- and PAA-coated lipoplexes did not induce agglutination after mixing with erythrocytes. In terms of biodistribution, siRNAs after intravenous administration of cationic lipoplexes were largely observed in the lungs, but those of CS-, PGA- and PAA-coated lipoplexes were in both the liver and the kidneys, indicating that siRNA might be partially released from the anionic polymer-coated lipoplexes in the blood circulation and accumulate in the kidney, although the lipoplexes can prevent the agglutination with blood components. To increase the association between siRNA and cationic liposome, we used cholesterol-modified siRNA (siRNA-Chol) for preparation of the lipoplexes. When CS-, PGA- and PAA-coated lipoplexes of siRNA-Chol were injected into mice, siRNA-Chol was mainly observed in the liver, not in the kidneys. In terms of the suppression of gene expression in vivo, apolipoprotein B (ApoB) mRNA in the liver was significantly reduced 48 h after single intravenous injection of PGA-coated lipoplex of ApoB siRNA-Chol (2.5 mg siRNA/kg), but not cationic, CS- and PAA-coated lipoplexes. In terms of toxicity after intravenous injection, CS-, PGA- and PAA-coated lipoplexes did not increase GOT and GPT concentrations in blood. From these findings, PGA coatings for cationic lipoplex of siRNA-Chol might produce a systemic vector of siRNA to the liver.”

mPEG-PLA for protein delivery

PolySciTech (www.polyscitech.com) provides a wide variety of PEG-b-PLA polymers (Polyvivo AK**) in our online catalog. Recently these kinds of polymer have been used along with lysine to generate biocompatible micelle formulation capable of carrying recombinant human erythropoietin showing the potential of this material to deliver protein based drugs with maintained bioactivity. Shi, Yanan, Fengying Sun, Dan Wang, Renyu Zhang, Changlin Dou, Wanhui Liu, Kaoxiang Sun, and Youxin Li. “Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG–PLA micelle.” Journal of nanoparticle research 15, no. 10 (2013): 1-10. http://link.springer.com/article/10.1007/s11051-013-2002-x

“Abstract: A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from −0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG–PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.”

inherent viscosity AO31

Some PolySciTech (www.polyscitech.com) products which are not DCM soluble can not be currently assayed in-house for molecular weight by GPC due to the solvent limitations of our GPC setup. For these products we often provide on demand the inherent viscosity of the polymer which can be utilized to achieve the molecular weight by the Mark-Houwink equation. For example the inherent viscosity of Poly(n-vinyl caprolactam) (PolyVivo AO31) lot# 30315JSG is 0.327 with a standard deviation of 0.002 (N=3, 30C, THF). If you are curious about the IV of any material which is not already shown on our catalog just contact us and we can obtain it for you on demand.

Trimethylene carbonate monomer available

PolySciTech (www.polyscitech.com) now provides trimethylene carbonate monomer (Polyvivo AM05) with no minimum order required. This monomer can be utilized to generate a variety of poly(trimethylene carbonates) and related derivatives.  Recent research has shown that these polymers are primarily degraded via enzymatic routes. Zhang, Zheng, Roel Kuijer, Sjoerd K. Bulstra, Dirk W. Grijpma, and Jan Feijen. “The in vivo and in vitro degradation behavior of poly (trimethylene carbonate).”Biomaterials 27, no. 9 (2006): 1741-1748. http://www.sciencedirect.com/science/article/pii/S0142961205008616

“Abstract: The in vivo and in vitro degradation behavior of poly(trimethylene carbonate) (PTMC) polymers with number average molecular weights of 69×103, 89×103, 291×103 and 457×103 g/mol (respectively abbreviated as PTMC69, PTMC89, PTMC291 and PTMC457) was investigated in detail. PTMC rods (3 mm in diameter and 4 mm in length) implanted in the femur and tibia of rabbits degraded by surface erosion. The mass loss of high molecular weight PTMC457 specimens was 60 wt% in 8 wks, whereas the mass loss of the lower molecular weight PTMC89 specimens in the same period was 3 times lower. PTMC discs of different molecular weights immersed in lipase solutions (lipase from Thermomyces lanuginosus) degraded by surface erosion as well. The mass and thickness of high molecular weight PTMC291 discs decreased linearly in time with an erosion rate of 6.7 μm/d. The erosion rate of the lower molecular weight PTMC69 specimens was only 1.4 μm/d. It is suggested that the more hydrophilic surface of the PTMC69 specimens prevents the enzyme from acquiring a (hyper)active conformation. When PTMC discs were immersed in media varying in pH from 1 to 13, the non-enzymatic hydrolysis was extremely slow for both the high and low molecular weight samples. It can be concluded that enzymatic degradation plays an important role in the surface erosion of PTMC in vivo.”

Thermogelling Cellulose

Looking for a biodegradable thermogel which forms minimal acid. PolySciTech has thermogelling Stearate-conjugated methyl cellulose (PolyVivo AO25) available for this application.  Similar materials have previously been described in publications relating to drug delivery. Read more at: Lee, Sang Cheon, Yong Woo Cho, and Kinam Park. “Control of thermogelation properties of hydrophobically-modified methylcellulose.” Journal of bioactive and compatible polymers 20, no. 1 (2005): 5-13. http://jbc.sagepub.com/content/20/1/5.short

“Abstract: Aqueous solutions that undergo reversible thermosensitive gelation around body temperature were developed based on hydrophobically-modified methyl cellulose (HMMC). The approach involved HMMC as the main component of aqueous compositions to provide a system with fast gelling properties, which has not been accomplished with aqueous solutions of unmodified methyl cellulose (MC). MC was modified with the stearyl group as a hydrophobic modifier by controlling the degree of modification. The gelation rate of aqueous solutions containing identical amounts of HMMC and NaCl increased as the temperature increased. The HMMC solutions gelled at a fixed temperature and concentration range, while the unmodified MC solutions did not show sol-to-gel transition. In addition, HMMC solutions exhibited much faster gelation than MC solutions at given polymer and NaCl concentrations. The HMMC/NaCl solutions exhibited the reversible gel-to-sol transition upon cooling below 25°C. The rate of sol-to-gel transition at body temperature, and the reversible gel-to-sol transition at room temperature, were modulated by adjusting the concentration of HMMC and NaCl, respectively. The HMMC/NaCl compositions provided a simple system for accurate control of the thermogelling temperature and the thermogelation rates.”

PLGA-PEG-Maleimide for crossing BBB

Did you know that PolySciTech also provides several thiol-reactive PLGA/PLA-PEG-Maleimides (AI20, AI40, AI47, AI48, AI49, AI50, AI52, AI53)? These polymers allow for the conjugation of peptides, antibodies, or other ligands so that the surface of the resultant nanoparticle can interface with cell-receptors. These same types of polymers have previously been used to aid the uptake of tempol across the blood-brain-barrier (BBB).  Read more at: Carroll, Richard T., Deepak Bhatia, Werner Geldenhuys, Ruchi Bhatia, Nicholas Miladore, Anupam Bishayee, and Vijaykumar Sutariya. “Brain-targeted delivery of Tempol-loaded nanoparticles for neurological disorders.” Journal of Drug Targeting 18, no. 9 (2010): 665-674. http://informahealthcare.com/doi/abs/10.3109/10611861003639796

“Abstract: Brain-targeted Tempol-loaded poly-(lactide-co-glycolide) (PLGA) nanoparticles (NPs) conjugated with a transferrin antibody (OX 26) were developed using the nanoprecipitation method. These NPs may have utility in treating neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. Central to these diseases is an increased production of reactive oxygen and nitrogen species which may take part in the development of these conditions. As proof of principle, the NPs were loaded with Tempol, a free radical scavenger that has been shown to be protective against oxidative insults. To enhance the delivery of NPs to the central nervous system (CNS), we conjugated the transferrin receptor antibody covalently to PLGA NPs using the NHS-PEG3500-Maleimide crosslinker. The NPs showed a particle size suitable for blood brain barrier (BBB) permeation (particle size 80–110 nm) and demonstrated a sustained drug release behavior. A high cellular uptake of antibody-conjugated NPs was demonstrated in RG2 rat glioma cells. The ability of the Tempol-loaded NPs to prevent cell death by resveratrol in RG2 cells was determined using the MTT assay. The conjugated NPs containing Tempol were more effective in preventing cell viability by resveratrol when compared with unconjugated NPs or free Tempol in solution. Our findings suggest that transferrin-conjugated NPs containing antioxidants may be useful in the treatment of neurodegenerative diseases.”

New Product mPEG-PVL PolyVivo AK67

PolySciTech has added block copolymers of poly(ethylene glycol)-poly(delta-valerolactone) to the current product offerings with the first product being PolyVivo AK67 (mPEG-PVL 5000-7000Da).  Similar polymers have been previously used in research to aid in solubilization and delivery of chemotherapeutic Camptothecin for cancer treatment. Chang, Yuan-Chia, and I. Chu. “Methoxy poly (ethylene glycol)-b-poly (valerolactone) diblock polymeric micelles for enhanced encapsulation and protection of camptothecin.” European Polymer Journal 44, no. 12 (2008): 3922-3930. http://www.sciencedirect.com/science/article/pii/S0014305708004849

“Abstract: Amphiphilic block copolymers, methoxy poly(ethylene glycol)-b-poly(valerolactone) (mPEG-b-PVL), were synthesized via ring opening polymerization of δ-valerolactone in the presence of methoxy poly(ethylene glycol) (mPEG). The copolymers form micelle-like nanoparticles by their amphiphilic characteristics and their structures were examined by Nuclear Magnetic Resonance (NMR). The sizes of nanoparticles ranged from 60 to 120 nm as measured by dynamic light scattering detection, and were larger with higher molecular weight of the copolymers. The Critical Micelle Concentration (CMC) of these nanoparticles in water decreased with increasing molecular weight of hydrophobic segment. Stability analysis showed that the micellar solutions maintain their sizes at 37 °C for six weeks without aggregation or dissociation. The lyophilization method was better than the evaporation method when camptothecin (CPT) was incorporated to the micelles. The former method yielded higher CPT loading efficiency and lower aggregation. The loading efficiency of CPT could be more than 96% and a steady release rate of CPT was kept for twenty six days. Moreover, the mPEG-b-PVL polymeric micelles offered good protection of CPT lactone form at 37 °C for sixteen days. The copolymers showed no cytotoxicity towards L929 mouse muscular cells when incubated for one day. Taken together, the mPEG-b-PVL copolymer has potential to be used for the delivery of CPT or other similar drugs.”

PolyVivo AV** fluorescent PLGA for nanoparticle tracking

Polyscitech provides a variety of fluorescently labelled PLGA’s (PolyVivo AV** series) for visualizing and tracking nanoparticles. These kinds of polymers have recently been used for confirmation of successful targeting of nanoparticles to tumor-associated macrophages as a potential treatment for cancer.: Zhu, Saijie, Mengmeng Niu, Hannah O’Mary, and Zhengrong Cui. “Targeting of tumor-associated macrophages made possible by PEG-sheddable, mannose-modified nanoparticles.” Molecular pharmaceutics 10, no. 9 (2013): 3525-3530. http://pubs.acs.org/doi/abs/10.1021/mp400216r

“Abstract: It is increasingly evident that tumor-associated macrophages (TAMs) play an important role in tumor invasion, proliferation, and metastasis. While delivery of drugs, imaging agents, and vaccines to TAMs was achieved by exploiting membrane receptors on TAMs, the uptake by normal macrophages remains an issue. In this communication, we report a PEG-sheddable, mannose-modified nanoparticle platform that can efficiently target TAMs via mannose–mannose receptor recognition after acid-sensitive PEG shedding in the acidic tumor microenvironment, while their uptake by normal macrophages in the mononuclear phagocyte system (MPS) organs was significantly reduced due to effective PEG shielding at neutral pH. These nanoparticles have the potential to target drugs of interest to TAMs, with decreased uptake by normal macrophages.”

mPEG-PLGA for delivery of drugs and cells

PolySciTech provides a variety of mPEG-PLGA block copolymers (polyvivo AK02, AK10, etc.). Recent research has shown how these copolymers can be utilized to create nanostructured microparticles capable of simultaneously delivering drug molecules and living cells for cell-based tissue engineering. Wen, Yanhong, Monica Ramos Gallego, Lene Feldskov Nielsen, Lene Jorgensen, Eva Horn Møller, and Hanne Mørck Nielsen. “Design and characterization of core–shell mPEG–PLGA composite microparticles for development of cell–scaffold constructs.” European Journal of Pharmaceutics and Biopharmaceutics 85, no. 1 (2013): 87-98. http://www.sciencedirect.com/science/article/pii/S0939641113001161

“Abstract: Appropriate scaffolds capable of providing suitable biological and structural guidance are of great importance to generate cell–scaffold constructs for cell-based tissue engineering. The aim of the present study was to develop composite microparticles with a structure to provide functionality as a combined drug delivery/scaffold system. Composite microparticles were produced by incorporating either alginate/dermatan sulfate (Alg/DS) or alginate/chitosan/dermatan sulfate (Alg/CS/DS) particles in mPEG–PLGA microparticles using coaxial ultrasonic atomization. The encapsulation and distribution of Alg/DS or Alg/CS/DS particles in the mPEG–PLGA microparticles were significantly dependent on the operating conditions, including the flow rate ratio (Qout/Qin) and the viscosity of the polymer solutions (Vout, Vin) between the outer and the inner feeding channels. The core–shell composite microparticles containing the Alg/DS particles or the Alg/CS/DS particles displayed 40% and 65% DS release in 10 days, respectively, as compared to the DS directly loaded microparticles showing 90% DS release during the same time interval. The release profiles of DS correlate with the cell proliferation of fibroblasts, i.e. more sustainable cell growth was induced by the DS released from the core–shell composite microparticles comprising Alg/CS/DS particles. After seeding fibroblasts onto the composite microparticles, excellent cell adhesion was observed, and a successful assembly of the cell–scaffold constructs was induced within 7 days. Therefore, the present study demonstrates a novel strategy for fabrication of core–shell composite microparticles comprising additional particulate drug carriers in the core, which provides controlled delivery of DS and favorable cell biocompatibility; an approach to potentially achieve cell-based tissue regeneration.”

Thermogel Discount

Want to try out a thermogel? Curious about this amazing delivery technique for injecting drugs and cells as a liquid which then turns into a solid in a warm body? For this month until February 15th PolySciTech has an extra 5% discount on thermogelling PolyVivo AK24 (PLGA-PEG-PLGA).  Input discount code: HRPJHYK to receive this discount at our online catalog here https://akinainc.com/polyscitech/products/polyvivo/sequential.php#BlockCopolymers