Formulation and characterization of a mucoadhesive hydrogel loaded with nanoparticles for the vaginal administration of metronidazole

The development of drug delivery systems for the vaginal administration of antimicrobic and antiviral drugs is a rapidly expanding area in the pharmaceutical field . A drawback of this route is represented by the physiological removal mechanism [1], which can be avoided using mucoadhesive formulations able to prolong drug residence time into the vaginal cavity. Semi-solid dosage forms, e.g. hydrogels formulated with bioadhesive polymers, have been intensively investigated and proposed as promising vaginal delivery systems, mainly due to their mucoadhesive properties. . However, the hydrophobic nature and low solubility in water of the most common antimicrobic and antiviral drugs have surely limited the development of hydrogel formulations for vaginal infectious diseases. A possible approach is to use amphiphilic block-copolymers, in order to increase water solubility of hydrophobic drugs[2]. Such nanocarriers are then incorporated inside the bioadhesive polymeric network of the hydrogel. In this study, mPEG5kDa-P(L)LGA di-block copolymer was employed to prepare nanoparticles loaded with the antimicotic drug metronidazole, which were then incorporated into a 1.5% Carbopol ® 974 hydrogel. Different concentration of nanoparticles (5-40 mg/ml) were screened in order to obtain a system with rheological properties (elastic modulus G’) comparable to those of Zidoval ® , the marketed vaginal Carbopol ® 974 hydrogel containing metronidazole. Moreover, spectrophotometric analysis demonstrated that our polymeric nanoparticles enhanced metronidazole solubility in water. In fact, the formulated Carbopol ® hydrogel in presence of 10 mg/ml mPEG5kDa-P(L)LGA nanoparticles was able to include a larger amount of metronidazole if compared with the same hydrogel without nanoparticles. Furthermore, the performance of these hydrogels in term of metronidazole release was evaluated. Nanoparticles were found not to influence the release profile of metronidazole from Carbopol ® hydrogel, In fact, both formulated hydrogels showed a metronidazole release rate comparable to Zidoval ®