Tailoring bromelain-loaded lipid–polymer hybrid nanoparticles for asthma management: fabrication and preclinical evaluation†

Poor response and associated side effects of available drugs in clinics have limited successful asthma management. Traditionally, bromelain has been found effective in asthma management; however, its use is limited by the need for high oral doses and poor bioavailability. Therefore, the present investigation was tailored to prepare bromelain-loaded lipid–polymer hybrid nanoparticles (Br-LPHNs) to enhance the oral bioavailability and therapeutic efficacy of bromelain in the management of allergic asthma. Br-LPHNs, consisting of a lipid core encapsulated in a biomimetic polymethylmethacrylate coating, were prepared utilizing the double emulsion solvent evaporation method. The drug release behavior, mucolytic potential and stability of the optimized formulation were evaluated. Pharmacokinetic and pharmacodynamic studies were executed in an allergen-induced asthma model. The optimized Br-LPHNs exhibited a nanosize (190.91 ± 29.48 nm) and high entrapment efficiency (89.94 ± 3.98%), along with gastro-resistant and sustained drug release behavior for up to 24 h. Using LPHNs as a carrier improved shelf life (∼6.99-fold) and bioavailability (6.89-fold) compared to pure bromelain. The optimized formulation significantly suppressed bronchial hyperresponsiveness, delayed the onset of bronchospasm and reduced its severity. Moreover, oxidative and immunological markers were significantly (p < 0.05) reduced, accompanied by the restoration of antioxidant enzyme levels to normal. Histopathological investigations also confirmed reduced tissue injury. Thus, the development of Br-LPHNs not only ensured in vitro and in vivo stability of bromelain but also offered a promising approach for asthma management.