Preparation and characterization of rifampicin-PLGA microspheres/sodium alginate in situ gel combination delivery system

Abstract

We prepared a complex drug delivery system consisted of rifampicin-poly(lactic-co-glycolic acid) (PLGA) microspheres in combination with sodium alginate in situ gel. The microspheres were obtained by using a solvent evaporation method, the mean diameter was 1.748μm and the span of particle distribution was 0.78. The combination delivery system was obtained by adding microspheres to sodium alginate solution followed by physically mixing. In an in vitro study of drug release monitored for 11 days, the release of rifampicin from combination delivery system was slower than microspheres. The cumulative release percent of rifampicin from combination delivery system was 91.83±1.26%, which was lower than 97.36±3.41% of rifampicin released from microspheres. An in vivo fluorescence imaging study suggests that the gel adhered to lungs within 24h, and microspheres stayed in lungs at least for 504h (21 days). In vivo drug release study indicates that the maximum local rifampicin concentration in lungs was 48.60±15.67μgmL−1 5h after administration. After 21 days, the local rifampicin concentration was 0.81±0.14μgmL−1, which was above the minimum inhibitory concentration of rifampicin. The combination delivery system significantly prolonged RFP release compared to microspheres, from which RFP released could only be detected for 10 days. This approach to control the release of rifampicin using PLGA microspheres/in situ gel combination delivery system in conjunction with interventional technology is useful for improving anti-tuberculosis treatment effectiveness for patients.