Title : Ligand-directed and pH-responsive liposomal systems for advanced pulmonary drug delivery
Abstract:
Pulmonary drug delivery has emerged as an attractive approach for achieving localized and systemic therapeutic effects while minimizing systemic exposure. The present study focuses on the development of a multifunctional liposomal delivery platform integrating ligand-mediated targeting and stimuli-responsive behavior to enhance intracellular delivery following pulmonary administration.
Multilamellar liposomal systems were engineered using biocompatible lipid components and designed to exhibit pH-responsive characteristics suitable for intracellular release in acidic environments. Surface functionalization was employed to facilitate preferential uptake by antigen-presenting cells, thereby improving cellular internalization and intracellular trafficking. The formulation strategy emphasized structural stability under physiological conditions while enabling triggered destabilization in response to acidic intracellular compartments.
The developed delivery systems were optimized and characterized for key physicochemical parameters including vesicle size, surface charge, morphology, encapsulation efficiency, and in vitro release behavior under physiologically relevant conditions. Stimuli responsiveness was evaluated using pH-dependent release studies, confirming minimal leakage at physiological pH and enhanced release under acidic conditions mimicking endosomal environments. Cellular uptake and intracellular localization were assessed using macrophage cell models, demonstrating improved internalization and intracellular distribution of the carrier system.
In vivo evaluation following pulmonary administration indicated enhanced biological responses compared with conventional non-responsive delivery approaches, highlighting the advantage of combining targeting and stimulus-triggered release within a single carrier platform.
Overall, the study demonstrates the potential of ligand-directed, pH-responsive liposomal systems as adaptable platforms for advanced pulmonary drug and vaccine delivery.

