Unveiling the potential of pulmonary surfactant-based nanocarriers for protein inhalation therapy

The study investigates the effect of pulmonary surfactant (PS) coating on the performance of lysozyme-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs). The NPs were fabricated using a double emulsification technique and optimized using the Box-Behnken experimental design (BBED). The NPs were assessed for size, polydispersity index (PDI), zeta potential, drug loading (DL%), and encapsulation efficiency (EE%). In addition, the optimized PLGA NPs were modified with either a neutral dipalmitoylphosphatidylcholine DPPC or an anionic dipalmitoyl phosphatidylglycerol (DPPG) with different molar ratios of PS to PLGA (PS: PLGA = 1:2, 1:1 and 2:1). These NPs were assessed for biological activity, drug release, mucus adhesion, mucus penetration, cellular uptake, toxicity, and in vivo destiny after intratracheal (IT) instillation to mice. Results showed a bi-phasic drug release, with no significant effect of PS on the release and biological activities of PLGA NPs. The PS@PLGA NPs improved mucus adhesion, decreased mucus penetration, and increased cellular internalization of PLGA NPs. In addition, ex vivo experiments demonstrated that DPPC@PLGA NPs and DPPG@PLGA NPs could adhere to mucus. These NPs created a thicker layer at the interface of the airway compared to unmodified PLGA NPs. Moreover, interaction of PS@PLGA NPs with BALF suggested improved mucoadhesive characteristics. Finally, the in vivo studies confirmed the precise distribution of all NPs in the lungs after IT administration. The study presents empirical evidence and scientific guidance for developing a lung surfactant-modified nanocarrier system for lung drug delivery.