Poly(ethylene carbonate)-containing polylactic acid microparticles with rifampicin improve drug delivery to macrophages

The Journal of Pharmacy and Pharmacology
Petra A PriemelHanne Mørck Nielsen

Abstract

Pulmonary delivery of antibiotics will decrease the required dose for efficient treatment of lung infections and reduce systemic side effects of the drug. The objective was to evaluate the applicability of poly(ethylene carbonate) (PEC) for the preparation of inhalable, antibiotic-containing particles. Rifampicin (RF)-loaded microparticles were prepared by electrospraying a carrier matrix of polylactic acid (PLA) with 0%, 5% and 10% PEC. Prepared particles had an aerodynamic diameter between 4 and 5 μm. Within 60 min, PEC-containing particles released 35-45% of RF, whereas PLA particles released only 15% of RF. Irrespective of particle composition, uptake of RF by macrophages was improved to 40-60% when formulated in microparticles compared to 0.4% for RF in solution, and intracellular localisation of particles was confirmed using confocal microscopy. Effect on macrophage and alveolar cell viability was similar for all particles whereas the minimal inhibitory concentrations against Pseudomonas aeruginosa and Escherichia coli for RF-containing PEC particles were twofold lower than for PLA particles, explained by the faster release of RF from PEC-containing particles. The inclusion of PEC in PLA microparticles increased the relea...Continue Reading

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