(13f) Hydrogel-Nanofiber Composite Systems for Drug Delivery

Poly(lactide-co-glycolide) (PLGA) is widely used in applications such as drug delivery because of its biodegradability and biocompatibility. The electrospinning technique was used to fabricate nanofibers from PLGA solution, and the resulting porous, fibrous mats were favorable for drug delivery. Model drugs, such as Myoglobin and Fluorescein Isothiocyanate (FITC)-Dextran, were incorporated in fibers during electrospinning and released as PLGA was eroded. Embedding the electrospun fibrous mats in a polyvinyl alcohol (PVA) hydrogel could provide mechanical strength for implantation and added diffusion barriers for drug release.

PLGA used in all studies had a lactide/glycolide molar ratio of 50:50 and a weight-average molecular weight of 76,500. Molecular weight of Myoglobin is 17,856 and that of FITC-Dextran is 250,000. All samples were incubated at 37°C in phosphate buffered saline (PBS) solution (pH = 7.4) for PLGA degradation and drug release studies. Dry weight loss, molecular weight change and morphology change of PLGA during incubation were used to evaluate the hydrolysis. Drug concentrations in incubating PBS solution were monitored to determine the release rate. Drug release was dependent on degradation of PLGA fibers and drug diffusion through PLGA and PVA. The influence of PVA and drugs on degradation rate was studied to provide additional information to correlate all components in the composite system. The obtained data will be used to predict and control the drug release rate.

In conclusion, we successfully incorporated about 1 wt% drugs into PLGA electrospun fibers. Fibers were found to swell and relax at the selected incubation condition and copolymer composition, which resulted in shrinkage of fibrous mats and decreasing of voids. Molecular weight of pure PLGA drops dramatically for the first two weeks of incubation, while weight loss increases significantly only after two weeks. Tiny pores were formed on pure PLGA fibers after two-week incubation, which proved that PLGA degradation was through bulk-erosion. Hydrolysis of pure PLGA was independent of fiber morphology. On the other hand, Myoglobin delayed the hydrolysis of PLGA for about one week, while PVA alleviated the extent of dry weight loss and raised the final molecular weight of incubated PLGA. Hydrogel could also significantly prevent fiber mats from shrinkage. Plots of dry weight loss of PLGA-Myoglobin fibrous mats and Myoglobin release from these fiber mats had similar shapes. After three weeks, significant weight loss and drug release began when the molecular weight of the incubated fiber mats stabilized. Initial burst was not significant for Myoglobin release from fiber mats, which indicated that Myoglobin did not gather at the surface of PLGA fibers. FITC-Dextran release from PLGA fiber mats showed initial burst. However, hydrogel-nanofiber composites eliminated the initial burst of FITC-Dextran release.