Development of inhalable multi-drug polymer carriers for combination therapies

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Summary

Cystic fibrosis (CF) is a complex respiratory condition, which has chronic infection and inflammation as hallmarks. The development of systems to deliver complementary therapies in one administration are therefore attractive. In this study, polymeric core-shell particles ( ) were developed using silk fibroin encapsulating the antibiotic ciprofloxacin as the shell layer, and the poly(L-lactic acid) (PLLA) carrying ibuprofen as the core. The particles were produced by oil-in-water emulsion (o/w) followed by spray-drying, resulting in a mixture of smooth and corrugated particles with a suitable size for inhalation. The high-resolution 2D chemical maps of individual particles obtained using synchrotron macro Attenuated Total Reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) spectroscopy, revealed the co-localization of the different drugs and polymers and thus the hierarchical structure. Furthermore, the release profiles of the drugs corroborated this type of structure, with a fast release of the shell antibiotic within the first 4 h, followed by a sustained release of the anti-inflammatory drug from the core. The polymeric particles did not show toxic effects on lung epithelial cells in vitro indicating the potential of these particles to be used for inhalation therapies.

Key Message

This study reports the development of inhalable core-shell microparticles to deliver a dual drug therapy with different release kinetics. The drugs were dispersed in individual polymer layers, preventing chemical interaction. The spatial drug distribution was assessed by chemical mapping using synchrotron macro ATR-FTIR technique, which corroborates the core-shell structure. This system has potential to address complex diseases as a multidrug carrier.