title: In situ gelling polyvalerolactone-based thermosensitive hydrogel for sustained drug delivery.
abstract: Biodegradable poly(ethyleneglycol)-poly(valerolactone)-poly(ethyleneglycol) [PEG-PVL-PEG] copolymers were synthesized through ring opening polymerization of δ-valerolactone (VL) followed by the coupling of monomethoxy poly(ethyleneglycol-poly(valerolactone) (mPEG-PVL) with hexamethylene diisocyanate (HDI). The copolymers were characterized by (1)H NMR, FT-IR, and GPC. Block copolymers of PEG and PVL with different VL/PEG molar ratios were successfully synthesized. One of the copolymers (Copolymer 2, PEG550-PVL6768-PEG550) displayed a sol-gel transition at a physiological temperature based on the test tube inverting method and rheological studies. The thermogelling copolymer demonstrated a characteristic crystalline peak for PVL block as determined by DSC and XRD analysis. In vitro release from the copolymer hydrogel matrix indicated that dexamethasone (DEX), a hydrophobic model drug, released comparatively slower than 5-fluoruracil (5-FU), a hydrophilic model drug, due to the potential partitioning of DEX into the PVL core. 5-FU in vitro release from copolymer 2 was 86% in 22 h, whereas only 14% of DEX was released in 24h. Cell viability studies confirmed that hydrogels composed of block copolymers are biocompatible. Copolymer 2 showed more than 80% relative cell viability at all concentrations, including concentrations greater than 200 fold CMC. In vivo gel formation studies indicate that gel integrity was maintained for 7 days upon subcutaneous injection into mice. These results indicate that PEG-PVL-PEG copolymers are suitable for drug delivery applications.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Gyan P
authors.initials: GP
authors.lastname: Mishra
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Reid
authors.initials: R
authors.lastname: Kinser
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA.
authors.forename: Igor H
authors.initials: IH
authors.lastname: Wierzbicki
authors.affiliation: School of Pharmacy and Chemistry, Drug Discovery, Delivery and Patient Care (DDDPC) Theme, Kingston University-London, United Kingdom; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR, USA. Electronic address: Adam.Alani@oregonstate.edu.
authors.forename: Adam W G
authors.initials: AW
authors.lastname: Alani
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage*; D004337:Drug Carriers; D020100:Hydrogels; D007783:Lactones / Q000737:chemistry*; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007783:Lactones; D011108:Polymers; D011092:Polyethylene Glycols; D003907:Dexamethasone
keywords: Biodegradable; In situ gelling; In vitro drug release; Polyester; Thermosensitive hydrogel; δ-Valerolactone