No abstract

This study investigated the effects of drug and polymer molecular weight on release kinetics from poly (G-co-glycolic acid)-methoxypoly(ethyleneglycol) (PLGA-mPEG) microspheres. Bovine serum albumin (BSA, 66 kDa), lysozyme (LZ, 13.4 kDa), and vancomycin (VM, 1.45 kDa) were employed as the model drugs, and encapsulated in PLGA-mPEG microspheres of different molecular weight. Release of macromolecular BSA was mainly dependent on diffusion of drug at/ near the surface of the matrix initially and dependent on degradation of matrix at later stages, while, the small drug of vancomycin seemed to depend totally on diffusion for the duration of the release study. The release behavior of lysozyme was similar to bovine serum albumin, except a shorter lag period. PLGA-mPEG molecular weight also affected the release behavior of bovine serum albumin and lysozyme, but not obviously. PLGAmPEG microspheres in smaller molecular weight seemed to degrade more quickly to obtain a mass lose and matrix erosion, and thus, an accelerated release rate of bovine serum albumin and lysozyme. Vancomycin released much faster than bovine serum albumin and lysozyme, and exhibited no lag period, as it is thought to be diffusion-controlled. Besides, vancomycin showed no difference in release behavior as PLGA-mPEG molecular weight change.

A novel biodegradable temperature-responsive copolymer, 4-arm star-shaped poly(D,L-lactic-coglycolic acid)-b-methoxy poly(ethylene glycol) (4sPLGA-mPEG), was synthesized via the arm-first method. The copolymer solution of various concentrations was prepared to form vaginal gels at body temperature, in order to encapsulate different anti-HIV drugs, anti-inflammatory drugs or contraceptive drugs. The 4sPLGA-mPEG block copolymer solutions were liquid at room temperature and only the 4sPLGA-mPEG block copolymer solutions with a copolymer concentration from 20 to 40 wt% show a sol-gel transition as the temperature was increased. The viscosity change associated with the sol-gel phase transition depended on the copolymer concentration and DL-lactide/glycolide (LA/GA) mol ratio. The in vitro and in vivo biodegradation and biocompatibility of a thermogelling polymeric material were examined in this study. The degradation of the copolymer gel, proceeded by hydrolysis of ester bonds, was followed by the erosion of the gel in a simulated vaginal fluid solution at body temperature for nearly one month. Mass loss and reduction of the molecular weight were detected. The LA/GA mol ratio was found to significantly influence the degradation profiles. The rapid in vivo gel formation was confirmed after subcutaneous injection of the copolymer solution into Sprague-Dawley (SD) rats. The in vivo degradation was slightly accelerated compared to in vitro hydrolysis, and the persistence time of the injected hydrogels in vivo was found to be tuned by the LA/ GA mol ratio. MTT assay and histological observations were used to examine the copolymer solution. Both in vitro and in vivo results illustrate acceptable biocompatibility of our materials. Collectively, our results show that the 4sPLGA-mPEG block copolymer is a promising candidate as a novel vaginal gel.

A series of star-shaped poly(D,L-lactic-co-glycolic acid)-b-methoxy poly(ethylene glycol) (PLGA-mPEG) block copolymers with varying PLGA/mPEG block weight ratios, mPEG block length, and arm numbers were synthesized and phase transition behaviors were investigated. Phase transition characteristics, such as critical gel concentration (CGC) and critical gel temperature (CGT), were closely related to the molecular structure of the star-shaped block copolymers. The CGC was mainly determined by the balance of hydrophobic PLGA and hydrophilic mPEG block (PLGA/mPEG block ratio). The CGTs showed a stronger dependence on mPEG block length and arm number. Also, the CGTs can be adjusted by adding mPEG homopolymer additives. The weight fraction of mPEG had a stronger influence on the CGT values than molecular weight of mPEG. In addition, the MTT assay and histological observations confirmed the acceptable biocompatibility of the star-shaped block copolymer. Hence, the star-shaped PLGA-mPEG block copolymer was a promising candidate as a novel injectable gel.

A well-developed BCP scaffolds coated with multilayer of HA/PLLA nanocomposites with interconnectivity, high porosity, and moderate compressive strength as well as good biocompatibility were fabricated for bone tissue engineering. After being multiply coated with HA/PLLA nanocomposites, the scaffolds maintained the BCP framework structure, and the porous network structure of scaffolds remained unchanged; however, the compressive strength was increased with the increase of coating layer number of HA/PLLA nanocomposites. The prepared scaffolds showed lower variation of pH values in SBF solution, and an increase of coating layer number led to the decrease of the biodegradation rate at different days. Moreover, the multilayer coating scaffolds had good cytocompatibility, showing no negative effects on cells growth and proliferation. Furthermore, the bone-like apatite layer was built obviously in the interface of scaffold after 21 days after implantation in SD rat muscle. In conclusion, the BCP scaffold coated with multilayer of HA/PLLA nanocomposites could be a candidate as an excellent substitute for damaged or defect bone in bone tissue engineering.