Friday, March 14, 2014

Polymer scaffolds/gels for delivery of bioactive agents

PolySciTech ( 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).

“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”
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