Gels, Vol. 11, Pages 567: Gelatin-Based Microspheres of Ciprofloxacin for Enhanced Lung Delivery and Biofilm Eradication in Pseudomonas aeruginosa Pulmonary Infections

Gels doi: 10.3390/gels11080567

Authors:
Luis Monrreal-Ortega
Rocío Iturriaga-Gallardo
Andrea Vilicic-Rubio
Pedro Torres
Patricio Leyton
Javier O. Morales
Tania F. Bahamondez-Canas
Daniel Moraga-Espinoza

Chronic lung infection is the main predictor of morbidity and mortality in cystic fibrosis (CF), and current pharmacological alternatives are ineffective against Pseudomonas aeruginosa infections. We developed ciprofloxacin (CIP) for inhalation, aiming at improving its solubility through the formation of an amorphous solid dispersion (ASD) using gelatin (GA). CIP and GA were dissolved in varying ratios and then spray-dried, obtaining CIP-GA microspheres in a single step. The dissolution rate, size distribution, morphology, and aerodynamic properties of CIP-GA microspheres were studied, as well as their antimicrobial activity on P. aeruginosa biofilms. Microspheres formulated with a higher GA ratio increased the dissolution of CIP ten-fold at 6 h compared to gelatin-free CIP. Formulations with 75% GA or more could form ASDs and improve CIP’s dissolution rate. CIP-GA microspheres outperformed CIP in eradicating P. aeruginosa biofilm at 24 h. The spray-drying process produced CIP-GA microspheres with good aerodynamic properties, as indicated by a fine particle fraction (FPF) of 67%, a D50 of 3.52 μm, and encapsulation efficiencies above 70%. Overall, this study demonstrates the potential of gelatin to enhance the solubility of poorly soluble drugs by forming ASDs. As an FDA-approved excipient for lung delivery, these findings are valuable for particle engineering and facilitating the rapid translation of technologies to the market.

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Luis Monrreal-Ortega www.mdpi.com