Abstract
Purpose: Direct delivery of aminoglycosides to the lungs was under extensive evaluations during the last decades. Because of large particle size, low density and porous structure, large porous particles (LPPs) are versatile carriers for this purpose. In this study, poly (lactic-co-glycolic acid) (PLGA) LPPs encapsulating gentamicin sulfate were prepared and in vitro characteristics of their freeze-dried powder as a dry powder inhaler (DPI) were evaluated. Methods: To prepare PLGA LPPs, a double emulsification-solvent evaporation method was optimized and gentamicin sulfate was post-loaded in the LPPs. in vitro characteristics including morphological features, thermal behavior, aerodynamic profile and cumulative drug release were evaluated by the scanning electron microscope (SEM), differential scanning calorimetry (DSC), next-generation cascade impactor (NGI) and Franz diffusion cell respectively. Results: The obtained results revealed that the preparation method was capable to produce spherical large homogenous highly porous particles. 94% of gentamicin sulfate released from LPPs up to 30 minutes. Mass median aerodynamic diameter (MMAD) and fine particle fraction (FPF) were 4.9 µm and 39% respectively. Conclusion: In this study, dry powder formulation composed of PLGA LPPs encapsulating gentamicin sulfate showed a promising in vitro behavior as a pulmonary delivery carrier. Improvements on the aerodynamic behavior and in vivo evaluations recommended for further developments.
Highlights
Local delivery of antibiotics directly to the pulmonary infections extensively studied during the last decades
Gentamicin sulfate is a member of this antibiotic family and as it is effective against the Pseudomonas aeruginosa, it has been applied in the pulmonary infections including cystic fibrosis, bronchiectasis, etc
In a study conducted by Garcia-Contreras et al, Capreomycin PLGA large porous particles (LPPs) which were produced by spray drying were effective to reduce the microbial load of the TB infected lung of the animals in comparison with the other treatment groups.[19]
Summary
Local delivery of antibiotics directly to the pulmonary infections extensively studied during the last decades. Because of the broad antibiotic spectrum, aminoglycosides were under the most evaluations for this purpose. Their high polarity has reduced their penetration ability through epithelia; high parenteral doses are needed to provide the therapeutic concentrations in the alveoli. These high doses may lead to some severe systemic side effects including renal impairment, neuromuscular toxicity and arising new bacterial resistance. Gentamicin sulfate is a member of this antibiotic family and as it is effective against the Pseudomonas aeruginosa, it has been applied in the pulmonary infections including cystic fibrosis, bronchiectasis, etc. Because of the hygroscopic nature of its raw material, its formulation and delivery process encountered several challenges.[3,4]
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