Development and Optimization of PNIPAAm Based Ensifentrine Loaded In-situ Nasal Gel for Improved Bioavailability

Objectives : The primary goal of this research was to develop and optimise PNIPAAm-based in-situ nasal gels for ensifentrine delivery, aiming to enhance drug bioavailability, retention time, and therapeutic outcomes for the treatment of COPD and asthma. Methods : The formulation was optimized using a 3² full factorial design, with the independent variables being the concentrations of PNIPAAm (1%, 3%, 5% w/v) and HPMC K4M (0.2%, 0.4%, 0.6% w/v). The dependent variables included gelation temperature, mucoadhesive strength, and drug release. Various characterization techniques including solubility studies, DSC, FTIR, viscosity, and ex-vivo permeation were employed to assess the performance of the nasal gel. Results : Research showed that ensifentrine achieved its maximum solubility value in phosphate buffer solution at pH 6.4 (3.02 ± 0.05 mg/mL). Between 27.1°C and 34.2°C stood as the gelation temperature range and the mucoadhesive strength extended from 0.98 N/cm² to 2.72 N/cm². Family MF7 demonstrated the highest drug permeation rate achieving 91.7 ± 3.1% of cumulative drug delivery throughout an 8-hour ex-vivo permeation experiment. The formulation stability test showed no considerable modifications during three months of accelerated storage. Conclusion : The PNIPAAm-based nasal gel formulation shows outstanding potential for maintaining drug release duration together with increased ensifentrine bioavailability. The favorable mucoadhesive and gelation properties of formulation MF7 provide evidence that it can serve as a potential alternative for improving drug systemic absorption through nasal administration for future clinical applications in chronic respiratory disease treatment.