Monthly Archives: March 2014

PolySciTech “Made in Indiana” manufacturer of the week

PolySciTech (www.polyscitech.com) has been named “Made in Indiana” manufacturer of the week (http://www.mep.purdue.edu/made/products.aspx?company=249). Additionally PST provides a wide array of PLGA-PEG copolymers. These types of copolymers have been the focus of a recent review article with respect to their drug delivery properties. Read more:  Tang, Xing, Zhang Keru, Juan Zhang, Wei Lu, Xia Lin, Yu Zhang, Bin Tian, Hua Yang, and Haibing He. “PEG-PLGA copolymers: their structure and structure-influenced drug delivery applications.” Journal of Controlled Release (2014). http://dx.doi.org/10.1016/j.jconrel.2014.03.026

“Abstract: In the paper, we begin by describing polyethylene glycol–poly lactic acid-co-glycolic acid (PEG–PLGA) which was chosen as a typical model copolymer for the construction of nano-sized drug delivery systems and also the types of PEG–PLGA copolymers that were eluted. Following this we examine the structure-influenced drug delivery applications including nanoparticles, micelles and hydrogels. After that, the preparation methods for nano-sized delivery systems are presented. In addition, the drug loading mode of PEG–PLGA micelles is divided into three aspects. Finally, the drug release profiles of PEG–PLGA micelles, both in terms of their in vitro and in vivo characteristics, are represented. PEG–PLGA copolymers are very suitable for the construction of micelles as carriers for insoluble drugs. This article reviews the structure and the different structure-influenced applications of PEG–PLGA copolymers, concentrating on the application of PEG–PLGA micelles. Keywords PEG–PLGA copolymers; Structure types; Drug delivery applications; Drug loading; Drug release; Target delivery”

Tang, 2014

mPEG-PTMC for treatement of brain cancer

PolySciTech (www.polyscitech.com) provides mPEG-PTMC (methoxy polyethylene glycol-b-poly(trimethylene carbonate) (e.g. Polyvivo AK66). Recent research has shown this material to be an effective carrier for paclitaxel to glioma cells. Read more: Jiang, Xinyi, Hongliang Xin, Xianyi Sha, Jijin Gu, Ye Jiang, Kitki Law, Yanzuo Chen, Liangcen Chen, Xiao Wang, and Xiaoling Fang. “PEGylated poly (trimethylene carbonate) nanoparticles loaded with paclitaxel for the treatment of advanced glioma: in vitro and in vivo evaluation.” International journal of pharmaceutics 420, no. 2 (2011): 385-394. http://dx.doi.org/10.1016/j.ijpharm.2011.08.052

“Abstract:  The aim of this study was to investigate the antitumor effect of paclitaxel (PTX)-loaded poly(ethylene glycol)–poly(trimethylene carbonate) (MPEG–PTMC) nanoparticles (NP) against gioblastoma multiforme (GMB). PTX-loaded NP (NP/PTX) were prepared with synthesized MPEG–PTMC by the emulsion/solvent evaporation technique. In vitro physiochemical characterization of those NP/PTX showed satisfactory encapsulation efficiency and loading capacity and size distribution. Cytotoxicity assay revealed that encapsulation in nanoparticles did not compromise the antitumor efficacy of PTX against U87MG cells. Pharmacokinetic study in rats demonstrated that the polymer micellar nanoparticles significantly enhanced the bioavailability of PTX than Taxol. In intracranial xenograft tumor-bearing mice, the accumulation of nanoparticles in tumor tissues increased distinctly after 12 h post i.v. More importantly, in vivo anti-tumor effect exhibited the median survival time of NP/PTX treated mice (27 days) was significantly longer than those of mice treated with Taxol (24 days), physiological saline (21 days) and blank MPEG–PTMC NP (21 days). Therefore, our results suggested that PTX-loaded MPEG–PTMC nanoparticles significantly enhanced the anti-glioblastoma activity of PTX and may be a potential vehicle in the treatment of high-grade glioma.”Jiang 2011 PEG-PTMC

PLGA fibrous mats for wound sealing

PolySciTech (www.polyscitech.com) provides a wide array of PLGA polymers. Recently these polymers have been in the news as Peter Kofinas’s group has been researching their use for an acetone sprayed nanofiber mat to seal wounds.  Read the news story here: http://cen.acs.org/articles/92/i12/SprayPolymer-Mats-Seal-Surgical-Incisions.html original research article: Behrens, Adam M., Brendan J. Casey, Michael J. Sikorski, Kyle L. Wu, Wojtek Tutak, Anthony D. Sandler, and Peter Kofinas. “In Situ Deposition of PLGA Nanofibers via Solution Blow Spinning.” ACS Macro Letters 3 (2014): 249-254. http://pubs.acs.org/doi/abs/10.1021/mz500049x

“ABSTRACT: Nanofiber mats and scaffolds have been widely investigated for biomedical applications. Commonly fabricated using electrospinning, nanofibers are generated ex situ using an apparatus that requires high voltages and an electrically conductive target. We report the use of solution blow spinning to generate conformal nanofiber mats/meshes on any surface in situ, utilizing only a commercial airbrush and compressed CO2. Solution and deposition conditions of PLGA nanofibers were optimized and mechanical properties characterized with dynamic mechanical analysis. Nanofiber mat degradation was monitored for morphologic and molecular weight changes in vitro. Biocompatibility of the direct deposition of nanofibers onto two cell lines was demonstrated in vitro and interaction with blood was qualitatively assessed with scanning electron microscopy. A pilot animal study illustrated the wide potential of this technique across multiple surgical applications, including its use as a surgical sealant, hemostatic, and buttress for tissue repair.”

PLGA-PEG-PLGA for oral chemotherapeutic agents

PolySciTech (www.polyscitech.com) provides a variety of PLGA-PEG-PLGA triblock copolymers through its polyvivo line (e.g. cat# AK12, AK15). Recently these types of polymers have been utilized to create Salidroside loaded lipid emulsions for improved oral bioavailability of this chemotherapeutic agent.  Read more: Fang, Dai-Long, Yan Chen, Bei Xu, Ke Ren, Zhi-Yao He, Li-Li He, Yi Lei, Chun-Mei Fan, and Xiang-Rong Song. “Development of Lipid-Shell and Polymer Core Nanoparticles with Water-Soluble Salidroside for Anti-Cancer Therapy.” International journal of molecular sciences 15, no. 3 (2014): 3373-3388.  Full-text available at: http://www.mdpi.com/1422-0067/15/3/3373/pdf

“Abstract: Salidroside (Sal) is a potent antitumor drug with high water-solubility. The clinic application of Sal in cancer therapy has been significantly restricted by poor oral absorption and low tumor cell uptake. To solve this problem, lipid-shell and polymer-core nanoparticles (Sal-LPNPs) loaded with Sal were developed by a double emulsification method. The processing parameters including the polymer types, organic phase, PVA types and amount were systemically investigated. The obtained optimal Sal-LPNPs, composed of PLGA-PEG-PLGA triblock copolymers and lipids, had high entrapment efficiency (65%), submicron size (150 nm) and negatively charged surface (−23 mV). DSC analysis demonstrated the successful encapsulation of Sal into LPNPs. The core-shell structure of Sal-LPNPs was verified by TEM. Sal released slowly from the LPNPs without apparent burst release. MTT assay revealed that 4T1 and PANC-1 cancer cell lines were sensitive to Sal treatment. Sal-LPNPs had significantly higher antitumor activities than free Sal in 4T1 and PANC-1 cells. The data indicate that LPNPs are a promising Sal vehicle for anti-cancer therapy and worthy of further investigation. Keywords: salidroside; lipid-shell and polymer-core nanoparticles (LPNPs); PLGA; antitumor”

mPEG-PCL/curcumin for cancer therapy

PolySciTech (www.polyscitech.com) provides a variety of mPEG-PCL block copolymers such as AK01 and others.  Recently these types of polymers have shown promise for use as micelle delivery agents for poorly soluble curcumin as part of cancer therapy.  Read more here: Danafar, Hossein, Soodabeh Davaran, Kobra Rostamizadeh, Hadi Valizadeh, and Mehrdad Hamidi. “Biodegradable m-PEG/PCL Core-Shell Micelles: Preparation and Characterization as a Sustained Release Formulation for Curcumin.” (2014). Full-text available: http://apb.tbzmed.ac.ir/Portals/0/Archive/Vol4No4/9-Davaran.pdf

“Abstract: Purpose: Among the potent anticancer agents, curcumin is known as a very efficacious against many different types of cancer cells, but its clinical applications has been limited because of hydrophobicity, low gastrointestinal absorption, poor bioavailability and rapid metabolism. In this way, a novel micellar delivery system with mPEG–PCL was synthesized and the release profile of the curcumin from the drug-loaded micelles was evaluated. Methods: In this study, curcumin was encapsulated within monomethoxypoly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) micelles through a single-step nano-precipitation method, leading to creation of curcumin-loaded mPEG-PCL (Cur/mPEG-PCL) micelles. Di-block mPEG-PCL copolymers were synthesized and used to prepare micelles. mPEG-PCL copolymer was characterized in vitro by HNMR, FTIR, DSC and GPC techniques. Then, mPEG–PCL copolymers with curcumin were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). Results: The findings showed the successful formation of smooth and spherical curcumin-loaded micelles. The encapsulation efficiency of curcumin was 88 ± 3.32%. The results of AFM revealed that the micelles have spherical shapes with size of 73.8 nm. The release behavior of curcumin from micelles was compared in different media. In vitro release of curcumin from curcumin-entrapped micelles was followed remarkably sustained profile. The sustained release of drug was hypothetically due to the entrapment of curcumin in core of micelles. Conclusion: The results indicate the successful formulation of curcumin loaded m-PEG/PCL micelles. From the results, It can be concluded that curcumin m-PEG-PCL micelles may be considered as an effective treatment strategy for cancer in the future. Keywords: mPEG-PCL, Micelles, Curcumin, Drug delivery”

PLA-PEG-PLA for creating anti-fouling surfaces

PolySciTech (www.polyscitech.com) provides a wide array of PLA-PEG-PLA triblock copolymers under the PolyVivo brand-name including AK08 and others.  Recently these polymers have shown promise for generating anti-fouling surfaces when mixed with PLA. Read more here: Shen, Peng, Kai Tu, Chang Yu Yang, Jian Li, and Ru Xu Du. “Preparation of Anti-Fouling Poly (Lactic Acid)(PLA) Hollow Fiber Membranes via Non-Solvent Induced Phase Separation.” Advanced Materials Research 884 (2014): 112-116. http://www.scientific.net/AMR.884-885.112

“Abstract: Anti-fouling PLA hollow fibers were fabricated using synthesized PLA-PEG-PLA copolymer as an additive to improve the hydrophilicity. The tri-block copolymer was prepared by ring-opening polymerization and a hydrophilic copolymer processing good compatibility with PLA molecule was obtained and utilized to fabricate membrane with PLA by NIPS. Elemental analysis showed that PLA-PEG-PLA could stably exist in membranes and endow the membrane with persistent hydrophilic. Thus the contact angle decreased nearly 20o with 5% PLA-PEG-PLA content, resulting in higher water permeability and BSA rejection which indicated the anti-fouling property of PLA membrane was improved.”

PLGA for bone scaffold use

PolySciTech (www.polyscitech.com) provides a wide variety of PLGA’s and related derivatives. Curious about learning more about PLGA. There is an excellent review article available in full-text version at the below link.  This article describes PLGA with an emphasis on bone tissue enginerring including such techniques as utilizing PLGA-NH2 endcap for anchoring bioactive molecules onto a scaffold. Read more here: Gentile, Piergiorgio, Valeria Chiono, Irene Carmagnola, and Paul V. Hatton. “An Overview of Poly (lactic-co-glycolic) Acid (PLGA)-Based Biomaterials for Bone Tissue Engineering.” International journal of molecular sciences 15, no. 3 (2014): 3640-3659. http://www.mdpi.com/1422-0067/15/3/3640/pdf

“Abstract: Poly(lactic-co-glycolic) acid (PLGA) has attracted considerable interest as a base material for biomedical applications due to its: (i) biocompatibility; (ii) tailored biodegradation rate (depending on the molecular weight and copolymer ratio); (iii) approval for clinical use in humans by the U.S. Food and Drug Administration (FDA); (iv) potential to modify surface properties to provide better interaction with biological materials; and (v) suitability for export to countries and cultures where implantation of animal-derived products is unpopular. This paper critically reviews the scientific challenge of manufacturing PLGA-based materials with suitable properties and shapes for specific biomedical applications, with special emphasis on bone tissue engineering. The analysis of the state of the art in the field reveals the presence of current innovative techniques for scaffolds and material manufacturing that are currently opening the way to prepare biomimetic PLGA substrates able to modulate cell interaction for improved substitution, restoration, or enhancement of bone tissue function. Keywords: bone; composite; PLGA; scaffolds; tissue engineering.”

PLGA airbrushed in operating rooms

Researchers are using a hardware-store airbrush to place polymer nanofibers on tissues in the operating room, as described in “Airbrushed Plymers Could Seal Surgical Incisisions,” an article published  in Chemical & Engineering News. They are using acetone as the solvent and carbon dioxide as the propellant in animal studies for now, and checking for better substances to use.

Polymer scaffolds/gels for delivery of bioactive agents

PolySciTech (www.polyscitech.com) provides a wide array of biodegradable polymers including PEG, PLGA’s, polyvalerolactones, poly(TMC)’s, PCL’s, and a variety of speciality copolymers. A great deal of these polymers can be utilized as component for, amongst other things, delivery of bioactive agents.  Recently an excellent review paper has been published which lays out the various strategies and techniques for applications of these delivery systems towards medicine. Read more: Nguyen, Minh Khanh, and Eben Alsberg. “Bioactive factor delivery strategies from engineered polymer hydrogels for therapeutic medicine.” Progress in Polymer Science (2014). http://dx.doi.org/10.1016/j.progpolymsci.2013.12.001

“Abstract: Polymer hydrogels have been widely explored as therapeutic delivery matrices because of their ability to present sustained, localized and controlled release of bioactive factors. Bioactive factor delivery from injectable biopolymer hydrogels provides a versatile approach to treat a wide variety of diseases, to direct cell function and to enhance tissue regeneration. The innovative development and modification of both natural- (e.g., alginate (ALG), chitosan, hyaluronic acid (HA), gelatin, heparin (HEP), etc.) and synthetic- (e.g., polyesters, polyethyleneimine (PEI), etc.) based polymers has resulted in a variety of approaches to design drug delivery hydrogel systems from which loaded therapeutics are released. This review presents the state-of-the-art in a wide range of hydrogels that are formed though self-assembly of polymers and peptides, chemical crosslinking, ionic crosslinking and biomolecule recognition. Hydrogel design for bioactive factor delivery is the focus of the first section. The second section then thoroughly discusses release strategies of payloads from hydrogels for therapeutic medicine, such as physical incorporation, covalent tethering, affinity interactions, on demand release and/or use of hybrid polymer scaffolds, with an emphasis on the last 5 years.

Abbreviations: GFs, growth factors; ALG, alginate; HA, hyaluronic acid; HEP, heparin; PEI, polyethyleneimine; PHEMA, poly(2-hydroxyethyl methacrylate); PEG, poly(ethylene glycol); PEO, poly(ethylene oxide); DEX, dextran; PPO, poly(propylene oxide); PPG, poly(propylene glycol); (PNIPAm), poly(N-isopropylacrylamide); PEO-PPO-PEO, poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide); Pluronic®, same as PEO-PPO-PEO; HDI, hexamethylene diisocyanate; PCL, poly(ɛ-caprolactone); PLA, poly(lactic acid); ROP, ring opening polymerization Sn(oct)2 stannous octoate; DEGDVE, di-(ethylene glycol) divinylether; p-TSA, p-toluenesulfonic anhydride; PGA, poly(glycolic acid); PHB, poly[(R)-3-hydroxybutyrate]; PLGA, poly(d,l-lactide-co-glycolide); MPEG, monomethoxy poly(ethylene glycol); DLLA, D,l-lactide; GA, glycolide; PVL, poly(δ-valerolactone); HB, (R)-3-hydroxybutyrate; EG, ethylene glycol; ATRP, atom transfer radical polymerization; MPC, poly(2-methacryloyloxyethyl phosphorylcholine); DEDBA, diethyl-meso-2,5-dibromoadipate; Cu(I)Br, copper(I) bromide; Me4Cyclam, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclo-tetradecane; RAFT, reversible addition-fragmentation chain transfer; PNIPAm-PMMA, poly(NIPAm-b-methyl methacrylate); macro-CTA, macromer containing chain transfer agent; AIBN, 2,2′-azobis(2-methylpropionitrile); MCPDB, S-methoxycarbonylphenylmethyl dithiobenzoate; AlCl3, aluminum chloride; IleOEt, l-isoleucine ethyl ester; LeuOEt, d,l-leucine ethyl ester; ValOEt, l-valine ethyl ester; PPF, poly(propylene fumarate); ZnCl2, zinc chloride; PLLA, poly(l-lactide); PDLA, poly(d-lactide); NaBH3CN, cyanoborohydride; PAA, poly(amidoamine); TMDP, 4,4-trimethylene dipiperidine; P(DEGMMA-co-MAA), poly(methoxydi(ethylene glycol) methacrylate-co-methacrylic acid); PAUU, poly(amino urea urethane); OSM, oligomer sulfamethazine; DMAP, 4-(dimethylamino)pyridine; DCC, N,N′-dicyclohexylcarbodiimide; PAE, poly(β-aminoester); BDA, 1,4-butandiol diacrylate; PAEU, poly(amino ester urethane); PANHS, palmitic acid N-hydroxysuccinimide; CD, cyclodextrins; HPMA, poly(N-(2-hydroxypropyl)methacrylamide); APMA, N-(3-aminopropyl)methacrylamide; PA, polyalanine; NCA, carboxy anhydrides; PLX, PPG-PEG-PPG bis(2-aminopropyl ether); AC, acryloyl chloride; Irgacure 651, 2,2-dimethoxy-2-phenylacetophenone; PEGDA, poly(ethylene glycol) diacrylate; PEGLADA, poly(ethylene glycol)-lactic acid-diacrylate; PHPMAlac, poly(N-(2-hydroxypropyl)methacrylamide lactate); Irgacure 2959, 4-(2-hydroxyethoxy)phenyl-(2-hydroxy-2-propyl)ketone; ALG-MA, methacrylated alginate; EDC, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride; NHS, N-hydroxysuccinimide; AEMA, 2-aminoethyl methacrylate; CMC, carboxymethylcellulose; PEGDM, poly(ethylene glycol) dimethacrylate; NORB, 5-norbornene-2-carboxylic acid; NASI, N-acryloxysuccinimide; DTP, dithiobis(propanoicdihydrazide); DTT, dithiothreitol; DEX-SH, thiolated-dextran; DEX-VS, dextran-vinyl sulfone; MMP, matrix metalloproteinase; NaIO4(NH4)2S2O8, sodium periodate ammonium persulfate; NaOCl, sodium hypochlorite; NaBH4, sodium borohydride; DTB, dithiobis(butyric dihydrazide); SPDP, N-succinimidyl 3-(2-pyridyldithio)propionate; DEX-CHO, aldehyde-modified dextran; AAD, adipic acid dihydrazide; Na2B4O7, sodium tetraborate; CMC-CHO, oxidized carboxymethylcellulose; CMDX-ADH, hydrazide-modified carboxymethyldextran; HA-CHO, oxidized hyaluronic acid; S-chitosan, N-succinyl-chitosan; HRP, horseradish peroxidase; TGase, transglutaminase; PVA, poly(vinyl alcohol); CDI, N,N′-carbonyldiimidazole; APS, ammonium persulfate; TEMED, N,N,N′,N′-tetramethylethylene diamine; P(PF-co-EG), poly(propylene fumarate-co-ethylene glycol); o-NBE, ortho-nitrobenzylether; BGP, β-glycerophosphate disodium salt; G, α-guluronic acid; CaSO4, calcium sulfate; CaCl2, calcium chloride; CaCO3, calcium carbonate; semi-IPN, semi-interpenetrating network; GAR IgG, goat anti-rabbit immunoglobulin G; AAm, acrylamide; MBA, N,N′-methylene bisacrylamide; AAc, acrylic acid; AFP, anti-AFP anti-α-fetoprotein antibody; PPxY, proline-rich peptide; DDD, docking and dimerization domain; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; AD, anchoring domain; AKAP, A-kinase anchoring protein; DMT, dexamethasone; SD, Sprague Dawley; 5-FU, 5-fluorouracyl; Ig, bovine γ-globulin; BSA, bovine serum albumin; siRNA, short interfering ribonucleic acid; GLP-1, glucagon-like peptide-1; DOX, doxorubicin; PAC, paclitaxel; AmB, amphotericin B; VEGF, vascular endothelial growth factor; GAG, glycosaminoglycan; β-NGF, β-nerve growth factor; PDGF-BB, platelet derived growth factor-BB; GDNF, glial-derived neurotrophic factor; bFGF, basic fibroblast growth factor; TGF-β1, transforming growth factor-β1; BMP-2, bone morphogenetic protein-2; SPR, surface plasmon resonance; SELEX, systematic evolution of ligands by exponential enrichment; PCR, polymerase chain reaction; ICG, indocyanine green; GOD, glucose oxidase; Con A, concanavalin A; PBA, phenylboronic acid; PNIPMAAm, poly(N-isopropylmethacrylamide); CaM, calmodulin; TFP, trifluoperazine; LCST, lower critical solution temperature; AMF, alternating magnetic field; XG, xanthan gum; UCNP, upconverting nanoparticle

Keywords: Polymerization; Polymeric biomaterial; Bioactive molecules; Controlled release; Release mechanism”

PolyVivo AK24 used for photosensitive hydrogel

Polyscitech (www.polyscitech.com) provides a variety of polymers through our distribution with Sigma-Aldrich. Recently a publication came out using PLGA-PEG-PLGA triblock (PolyVivo AK24, Aldrich # 764817) for generating a photosensitive hydrogel network. Read more at: Ninh, Chi, Madeline Cramer, and Christopher J. Bettinger. “Photoresponsive hydrogel networks using melanin nanoparticle photothermal sensitizers.” Biomaterials Science (2014). http://pubs.rsc.org/en/content/articlelanding/2014/bm/c3bm60321k/unauth#!divAbstract

“ABSTRACT: Photoreconfigurable and photodegradable polymeric networks have broad utility as functional biomaterials for many applications in medicine and biotechnology. The vast majority of these functional polymers are synthesized using chemical moieties that may be cytotoxic in vivo. Materials synthesized from these substituents also pose unknown risk upon implantation and thus will encounter significant regulatory challenges prior to use in vivo. This work describes a strategy to prepare photodegradable hydrogel networks that are composed of well-characterized synthetic polymers and natural melanin pigments found within the human body. Self-assembled networks of poly(L-lactide-co-glycolide)-poly(ethylene glycol) ABA triblock copolymers are doped with melanin nanoparticles to produce reconfigurable networks based on photothermal phase transitions. Self-assembled hydrogel networks with melanin nanoparticles exhibit a storage modulus ranging from 1.5 ± 0.6 kPa to 8.0 ± 7.5 kPa as measured by rheology. The rate of UV-induced photothermal heating was non-monotonic and varied as a function of melanin nanoparticle loading. A maximum steady state temperature increase of 20.5 ± 0.30 °C was measured. Experimental heating rates were in close agreement with predictions based on attenuation of light in melanins via photothermal absorption and Mie scattering. The implications of melanin nanoparticles on hydrogel network formation and light-induced disintegration were also characterized by rheology and dynamic light scattering. Taken together, this class of photoreconfigurable hydrogels represents a potential strategy for photodegradable polymers with increased likelihood for clinical translation.”