Design and characterization of nasal release system using ritonavir-imprinted pHEMA nanoparticles

The exceptional ability of molecularly imprinted polymers (MIPs) to recognize specific molecular structures has recently facilitated their use in biomedical applications, including drug release. Controlled nasal drug release techniques effectively target specific tissues with optimal doses, timing, and location for therapeutic effects. This approach is advantageous due to the slightly acidic pH and low enzymatic activity in this region. MIPs are employed in these areas to enhance specificity and efficacy in drug release systems. This study aims to design an effective controlled nasal drug release system by imprinting the antiretroviral drug Ritonavir (RTV) onto pHEMA-based molecularly imprinted nanoparticles. Attenuated total reflection Fourier-transform infrared spectroscopy (FTIR-ATR), zeta-size analysis, and scanning electron microscopy (SEM) were used to characterize the nanoparticles, verifying their spherical shape, content and consistent size distribution. Zeta-size analysis revealed that RTV-imprinted p(HEMA-MATrp) nanoparticles had an average size of 88.46 nm with a polydispersity index of 0.279. The MIP nanoparticles possessed a specific surface area of 628.34 m²/g. In vitro release studies showed controlled release behavior of RTV-loaded nanoparticles, fitting the Korsmeyer-Peppas model. At 2.0 mg/mL, 71% cumulative release was observed after 10 h. The cumulative release of the was lowest at pH 4.0 (26%) and highest at pH 7.4 (32%) for 1.0 mg/mL loaded p(HEMA-MATrp) nanoparticles. MTT cytotoxicity tests on L929 cells indicated reduced cytotoxicity and good biocompatibility. These results suggest RTV-imprinted p(HEMA-MATrp) nanoparticles as an effective drug release system for antiretroviral therapies.