Tailoring of bromelain loaded lipid polymer hybrid nanoparticles for asthma management: Fabrication and preclinical evaluation

Abstract

Poor response along with associated side effects of available drugs in clinics has limited the successful asthma management. Traditionally, bromelain has been found effective in asthma management. However, high oral dose and poor bioavailability limits its use. Therefore, present investigation was tailored to prepare bromelain loaded lipid polymer hybrid nanoparticles (Br-LPHNs) to enhance oral bioavailability and therapeutic efficacy of bromelain in allergic asthma management. Br-LPHNs having a lipid core encapsulated in biomimetic polymethylmethacrylate coat were prepared utilizing double emulsion solvent evaporation method. Drug release behavior, mucolytic potential and stability of optimized formulation were evaluated. Pharmacokinetic and pharmacodynamic studies were executed in allergen-induced asthma model. Optimized Br-LPHNs manifested nanosize (190.91±29.48 nm) and high entrapment efficiency (89.94±3.98%) with gastro-resistant and sustained drug release behavior upto 24h. LPHNs as carrier improved shelf life (~6.99-fold) and bioavailability (6.89-fold) relative to neat bromelain. Optimized formulation significantly suppressed bronchial hyperresponsiveness, delayed bronchospasm induction and reduced spasm severity. Moreover, oxidative and immunological markers were significantly (p<0.05) diminished along with restoration of antioxidant enzyme to normal level. Histopathological investigations also assured reduced tissue injury. Thus, Br-LPHNs development not only ensured in-vitro and in-vivo bromelain stability but also offered a promising option for managing asthma.