Novel, bioerodible, thermosensitive poly(NIPAAm-co-dimethyl-γ-butyrolactone), with hydrolysisdependent thermosensitivity, were synthesized by radical polymerization with varying dimethyl-γ-butyrolactone content and the properties of the copolymers were characterized using Differential Scanning Calorimetry (DSC), High Performance Liquid Chromatography (HPLC) in conjunction with Static Light Scattering, Fourier Transformed Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR) and acid titration. The lower critical solution temperature (LCST) of the copolymers decreased with increasing dimethyl-γ-butyrolactone content, but then increased after ring-opening hydrolysis of the dimethyl-γ-butyrolactone side group. FTIR and NMR spectra showed the copolymerization of these two monomers and the hydrolysis-dependent ring-opening of the dimethyl-γ-butyrolactone side group. It was also found that there are no low-molecular-weight byproducts but rather dissolution of the polymer chains at 37°C during the time frame of application. Models of the kinetics suggest that the hydrolysis reaction is self-catalytic due to an increase in hydrophilicity, and thus accessible water concentration, caused by ring-opening of the dimethyl-γ-butyrolactone.

No abstract

A thermosensitive, injectable and bioresorbable polymer hydrogel, Poly(N-isopropylacrylamide-co-dimethyl-γ-butyrolactone acrylate-co-acrylic acid) (poly(NDBA)), was synthesized by radical copolymerization with 7.00 mol.% dimethyl-γ-butyrolactone acrylate in tetrahydrofuran (THF). The chemical composition was determined by acid titration in conjunction with 1H NMR quantification. The molecular weight and polydispersity were determined by gel permeation chromatography (GPC) in conjunction with static light scattering. The degradation properties of the polymer hydrogel were characterized using differential scanning calorimetry (DSC), percentage mass loss, cloud point test and swelling ratio over time. It was found that the initial LCST of the polymer is between room temperature and body temperature and that it takes about 2 weeks for the LCST to surpasses body temperature under physiological conditions. An indirect cytotoxicity test indicated that this copolymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells. The in vivo-gelation and degradation study showed good agreement with in vitro-degradation findings and no detrimental effects to adjacent tissues were observed after the complete dissolution of the polymer.

The focus of this study was to examine the biocompatibility, time-dependent LCST, and bioerodable properties of a copolymer system composed of NIPAAm, Dimethyl-γ-Butyrolactone (DMBL), and Acrylic Acid (AAc). Sprague Dawley rats were subcutaneously injected with 25 wt% solutions of Poly(NIPAAm-co-DMBL-co-AAc). At predetermined times, animals were sacrificed and polymer implants were recovered for characterization via 1H-NMR. In addition, polymer-contacting tissue sections were harvested and processed for histology. The biocompatibility of the implants was assessed by counting the number of fibroblasts and leukocytes present at the tissue-implant interface. The LCST data obtained from the in vivo implants was shown to agree with that of in vitro findings. Implant mass was shown to decrease after 4 days, indicating accelerated diffusion rates with increased implant swelling, hydrolytic degradation was confirmed with 1H-NMR measurements. The cellular presence at the copolymer implant-tissue interface was shown to return to that of normal tissue 30 days post-implantation, which suggests a normal wound healing response.

A thermosensitive, bioresorbable and in situ gelling co-polymer, poly(N-isopropylacrylamide-co-dimethyl-gamma-butyrolactone acrylate-co-acrylic acid), was synthesized by radical co-polymerization with varying dimethyl-gamma-butyrolactone acrylate (DBA) content. The materials properties were characterized using differential scanning calorimetry, gel-permeation chromatography in conjunction with static light scattering, Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) and acid titration. The initial lower critical solution temperature (LCST) of the synthesized co-polymer is between room temperature and body temperature. With the increase of DBA content, the LCST decreases, but then increases after the ring-opening hydrolysis of the DBA side-group. The FT-IR and NMR spectra show the co-polymerization of three monomers, as well as the hydrolysis-dependent ring-opening of the DBA side-group. The addition of acrylic acid increases the initial LCST and accelerates the degradation rate of the co-polymer. An indirect cytotoxicity test indicated that this co-polymer has relatively low cytotoxicity as seen with 3T3 fibroblast cells.