Development and pharmacokinetic evaluation of novasomes encapsulated roflumilast loaded nanoparticles of thiolated chitosan for transnasal delivery

Bioavailability of roflumilast (RFT) upon oral administration is decreased because of gastrointestinal adverse effects and hepatic first pass metabolism. Nasal administration might increase the bioavailability of RFT and its quick onset of action because phosphodiesterase-4 inhibitors are present in several lung areas. The current study’s objective was to formulate RFT-loaded nanoparticles of thiolated chitosan (TCS) and novasomes (NOV5) to enhance pharmacokinetics and mucoadhesion. The nanoparticles were prepared utilizing the ionic-gelation technique. RFT-loaded NOV5 were produced using an optimized formulation of TCS nanoparticles (TCSNP5). Thermal stability, mucoadhesion, drug dissolution, and toxicity were all assessed for nanoparticles. TCS was confirmed by ¹ H-NMR analysis and the Fourier transform infrared (FTIR) technique, which showed peaks at 3.5ppm and 1247 cm ^-1 , respectively. The nanoparticles’ zeta potential was -17.5 mV, and their diameter was 50.72nm. The best results for mucoadhesion, drug loading, entrapment efficiency, and RFT release were shown by optimized formulations (TCSNP5 and NOV5). The toxicity of nanoparticles and NOV5 was evaluated using the Caco-2 cell line. Comparing, trans-nasal delivery of NOV5 formulation with the reference Daliresp® tablets, a 3-fold increase in the bioavailability of RFT was observed along with3.3-fold improvement in mucoadhesion. Therefore, nasal administration of RFT-loaded NOV5 may represent an innovation in the treatment of chronic obstructive pulmonary disease (COPD).