Improved bioavailability of raloxifene hydrochloride through nasal administration of poly (methyl vinyl ether-co-maleic acid) nanoparticles in ovariectomized rats

Objective(s): To improve the low bioavailability of Raloxifene hydrochloride (RH), which is just ۲% through oral administration, an in situ mucoadhesive thermoreversible gel loaded with RH nanoparticles was formulated using Pluronic F۱۲۷. Materials and Methods: Mucoadhesion of the gels was modulated using Carbopol ۹۳۴, Xanthan gum, and HPMC K۴M as mucoadhesive polymers. The formulations containing ۱۸% Pluronic and ۰.۲% Xanthan gum or ۰.۵% HPMC were considered as the optimized formulation based on their pH, gelation temperature, mucoadhesive strength, gel strength, viscosity, drug content, histopathological, and pharmacodynamic studies in ovariectomized rats. Results: The gelation temperatures were ۳۳.۶۳±۰.۳۸ °C for Xanthan gum (۰.۲%) and ۳۷.۱۸±۰.۷۱ °C for HPMC (۰.۵%). Also, the ۵۱۷۵۸.۶۷±۶۲.۱۷ dyn/cm۲ mucoadhesive strength was seen in HPMC ۰.۵% and ۱۴۸۶۷.۳۳±۱۹۲.۶۰ dyn/cm۲ in Xanthan gum ۰.۲%. The drug released from the gel containing HPMC (۰.۵%) and Xanthan gum (۰.۲%) at ۱۸۰ min was ۹۸.۲ ± ۰.۹% and ۹۲.۲ ± ۵.۶%, respectively. Serum calcium, phosphorus, and alkaline phosphatase significantly decreased in ovariectomized rats treated with oral estradiol valerate (as the standard treatment), and ovariectomized rats received nasal gels containing RH nanoparticles in comparison to the group with no treatment (P<۰.۰۵). Histopathological results indicated no adverse effects on the nasal mucosa following the administration of RH nanoparticle gels. Also, compared with the untreated drug, the nasal gel of RH nanoparticles showed an AUC۰-۲۴ that was ۵.۵-fold higher, indicating a significant improvement in RH relative bioavailability (P<۰.۰۵). Conclusion: These results suggest that the thermoreversible nasal gel formulation of RH can be used as a safe drug-delivery system.

کلیدواژه ها:

Nasal delivery ، Ovariectomized rats ، Pluronic ، Poly (Methyl vinyl ether-co-maleic acid) nanoparticles ، Raloxifene hydrochloride ، Thermoreversible gels