MUCOADHESIVE AMINOPHYLLINE-LOADED NANOPARTICLES FOR PULMONARY DELIVERY: CHARACTERIZATION, MUCIN INTERACTION AND IN VITRO SAFETY EVALUATION
Polymeric nanoparticles, pulmonary drug delivery, mucoadhesion, controlled release.
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Polymeric nanoparticles, pulmonary drug delivery, mucoadhesion, controlled release. |
Aminophylline is a methylxanthine bronchodilator with anti-inflammatory properties. However, its clinical use is limited by a narrow therapeutic index and concentration-dependent adverse effects. In this context, pulmonary nanocarriers have emerged as a promising strategy to improve local drug retention while minimizing systemic exposure and dose-related toxicity. Therefore, this study developed aminophylline-loaded poly(ε-caprolactone) nanoparticles, with and without chitosan surface functionalization, and investigated their physicochemical characteristics, mucus interaction, in vitro release profile and cytocompatibility as a potential pulmonary drug delivery platform. Aminophylline nanoparticles (AM-PCL) and chitosan coated aminophylline nanoparticles (AM-PCL-CHI) exhibited mean hydrodynamic diameters of 194 ± 10 nm and 223 ± 4.9 nm, respectively, with low polydispersity indices, and remained colloidally stable for 30 days. Chitosan coating changed the zeta potential from −19.2 ± 3.34 to +25.0 ± 2.10 mV, while significantly increasing encapsulation efficiency from 16.25 ± 5.70% to 34.60 ± 1.75% and drug loading from 7.30 ± 2.20% to 12.30 ± 0.60%. Enhanced nanoparticle-mucin interactions, consistent with a mucoadhesive surface, were demonstrated by electrostatic interaction with mucin and turbidimetric analysis. The NPs provided modified aminophylline release for up to 12 h, with the Higuchi model showing the best fit (R² = 0.9835), suggesting diffusion-controlled release from the polymeric matrix. Cytocompatibility was concentration-dependent, with reduced cell viability mainly observed at nanoparticle concentrations above 25 µg/mL. Overall, chitosan functionalization improved the pharmaceutical performance of aminophylline-loaded PCL nanoparticles by increasing drug retention, enhancing nanoparticle–mucin interactions, and modified drug delivery Therefore, these findings support the further development of this mucoadhesive nanosystem as a promising platform for pulmonary drug delivery.