Mucoadhesive hydrogel loaded with nanoparticles for the vaginal release of saquinavir mesylate

Nowadays HIV/AIDS is recognized as one of the most significant health concerns of our society. Although HIV infections have slowed in recent years, the continued presence on global level of a large number of untreated HIV-infected patients means that the infected population is likely to grow [1]. In absence of vaccines, current research has been focused on the developing of new strategies that can prevent/reduce the heterosexual transmission of the virus. The aim of this project was to formulate and characterize an intravaginal delivery system for saquinavir mesylate (the first protease inhibitor approved by the FDA and widely used in the antiHIV therapy). The drug was encapsulated in polymeric nanoparticles and then formulated into a vaginal hydrogel to enhance the retention time within the vaginal cavity and to provide an easy selfadministration [2]. The physiological removal mechanism, that is a limiting factor in the vaginal administration, can in fact be avoided using a mucoadhesive formulation, able to prolong the drug residence time into the vaginal cavity. In this study, mPEG-PLGA di-block copolymers were employed to prepare nanoparticles loaded with saquinavir mesylate, which were then incorporated into a 1.5% Carbopol ® 974 hydrogel.Various mPEG-PLGA di-block copolymers (with different mPEG/PLGA ratio) were screened for their ability to form stable nanoparticles. Different concentrations of nanoparticles were then tested to evaluate their influence on the gel strength in order to obtain a system with the desired rheological properties. The presence of nanoparticles was found to cause a decrease in the strength of the hydrogel. Nevertheless, Carbopol ®974 gives a hydrogel (from a rheological point of view) at any tested concentration of nanoparticles. Encapsulation efficiency of saquinavir mesylate loaded nanoparticles was finally determined by HPLC analysis resulting in 55%.