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In Situ Gelling Polyvalerolactone-Based Thermosensitive Hydrogel for Sustained Drug Delivery

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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 ¹H 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 hr, whereas only 14% of DEX was released in 24 hr. 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.
  • Keywords: Biodegradable, In situ gelling, Thermosensitive hydrogel, Polyester, In vitro drug release, δ–valerolactone
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  • Mishra, G. P., Kinser, R., Wierzbicki, I. H., Alany, R. G., & Alani, A. W. G. (2014). In situ gelling polyvalerolactone-based thermosensitive hydrogel for sustained drug delivery. European Journal of Pharmaceutics and Biopharmaceutics, 88(2), 397-405. doi:10.1016/j.ejpb.2014.06.004
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  • 88
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  • 2
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  • This study was supported by the grant from AACP New Pharmacy Faculty Research Award Program, Medical Research Foundation of Oregon New Investigator Grant, and Oregon State University-Startup fund.
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