Continuous release of
dexamethasone from PLGA
microsphere/PVA
hydrogel composites has been shown to suppress the inflammatory tissue reaction in response to subcutaneously implanted foreign material for a period of one month. The scope of the present work is to investigate whether suppressing the initial acute inflammatory phase with fast releasing
dexamethasone-PLGA
microsphere/PVA composites (that release the
drug over a period of one week) would prevent the development of a
foreign body reaction in response to implantation in the subcutaneous tissue using a rat model.
METHODS:
Dexamethasone loaded PLGA
microspheres were prepared using the
solvent evaporation method. In vitro release from
microspheres was analyzed using USP apparatus 4 in
phosphate buffered saline (PBS) at 37 degrees C. Composites were fabricated in 18G needles by freeze-thaw cycling the PVA/
microsphere dispersion. The composites were implanted in the subcutaneous tissue of anesthetized rats. The pharmacodynamic effect was evaluated by histological examination of the tissue surrounding the composites at pre-determined time points.
RESULTS: In vitro release studies showed that most of the
drug entrapped in the
microspheres was released within one week. At days 3 and 8, these fast releasing
dexamethasone containing composites suppressed the acute phase of
inflammation but did not prevent the development of an inflammatory reaction after
dexamethasone was completely released from the composites. By day 30, chronic
inflammation and
fibrosis were observed in the tissue surrounding the
drug-containing composites. On days 3 and 8, the number of inflammatory cells in the vicinity of the
dexamethasone containing composites was similar to that in normal tissue. However, the number of inflammatory cells was higher in
drug-containing composites as compared to
drug-free composites by day 30. This was due to the
inflammation being in a more advanced stage in
drug-free composites where a granulomatous reaction had already developed.
CONCLUSION: