Purpose: To produce low releasing composite microparticles (MP) encapsulating second-line antitubercular drugs, namely capreomycin sulfate (C) and ofloxacin (Ofx), for pulmonary delivery. Methods: Composite MP were prepared by spray-drying a S/O dispersion of lecithin-chitosan particles containing C and Ofx in poly(lactide-co-glycolide) (PLGA) solution. C and Ofx were entrapped in lecithin-chitosan particles by a W/O/W double emulsion/solvent evaporation method. The drugs were dissolved in water and 0.5M acetic acid solutions, respectively, and emulsified into a 2% lecithin dichloromethane-acetone solution, then transferred into a chitosan solution. After solvent evaporation, the particles were centrifuged, washed and freeze-dried. Different batches were then reconstituted into a PLGA solution and spray-dried. The obtained composite MP preparations were characterized for size by SPOS and dynamic light scattering, morphology by SEM and drug content by HPLC and UV-vis methods. In vitro drug release was evaluated in phophate buffer solution pH 7.4, 37°C, comparing the composite MP with conventional MP obtained by direct spray-drying of drug-polymer solutions and emulsions. Results: C and Ofx were successfully entrapped into lecithin-chitosan particles yielding about 30 and 50% w/w drug content, respectively. Such particles possessed a mean diameter of 0.5-2 μm and irregular shape. The composite PLGA MP were larger with volume mean diameters around 8-10 μm with a good morphology with around 10% drug content (w/w). The in vitro release was more sustained for the composite PLGA MP compared to conventional PLGA MP. Conclusion: These results suggest that the developed composite PLGA MP, although requiring some improvements, possess potential as pulmonary delivery systems of second-line antitubercular drugs and potentiality to target alveolar macrophages as a result of a reduced initial release, which may warrant high intracellular payloads.
Novel ofloxacin and capreomycin sulfate loaded spray-dried composite particles for tuberculosis inhalation therapy
GIOVAGNOLI, Stefano;BLASI, PAOLO;SCHOUBBEN, Aurelie Marie Madeleine;ROSSI, Carlo;RICCI, Maurizio
2010
Abstract
Purpose: To produce low releasing composite microparticles (MP) encapsulating second-line antitubercular drugs, namely capreomycin sulfate (C) and ofloxacin (Ofx), for pulmonary delivery. Methods: Composite MP were prepared by spray-drying a S/O dispersion of lecithin-chitosan particles containing C and Ofx in poly(lactide-co-glycolide) (PLGA) solution. C and Ofx were entrapped in lecithin-chitosan particles by a W/O/W double emulsion/solvent evaporation method. The drugs were dissolved in water and 0.5M acetic acid solutions, respectively, and emulsified into a 2% lecithin dichloromethane-acetone solution, then transferred into a chitosan solution. After solvent evaporation, the particles were centrifuged, washed and freeze-dried. Different batches were then reconstituted into a PLGA solution and spray-dried. The obtained composite MP preparations were characterized for size by SPOS and dynamic light scattering, morphology by SEM and drug content by HPLC and UV-vis methods. In vitro drug release was evaluated in phophate buffer solution pH 7.4, 37°C, comparing the composite MP with conventional MP obtained by direct spray-drying of drug-polymer solutions and emulsions. Results: C and Ofx were successfully entrapped into lecithin-chitosan particles yielding about 30 and 50% w/w drug content, respectively. Such particles possessed a mean diameter of 0.5-2 μm and irregular shape. The composite PLGA MP were larger with volume mean diameters around 8-10 μm with a good morphology with around 10% drug content (w/w). The in vitro release was more sustained for the composite PLGA MP compared to conventional PLGA MP. Conclusion: These results suggest that the developed composite PLGA MP, although requiring some improvements, possess potential as pulmonary delivery systems of second-line antitubercular drugs and potentiality to target alveolar macrophages as a result of a reduced initial release, which may warrant high intracellular payloads.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
