Development of Cervix-Targeted Hydrogel Carrier for Carboplatin-Loaded Nanosponges: In-Vitro and Ex-Vivo Evaluation

The present work was aimed to design a novel hydrogel carrier containing carboplatin-loaded nanosponges as mucosal application for treatment of cervical cancer. Ethylcellulose-based carboplatin-loaded nanosponges, developed by double emulsion solvent evaporation were incorporated into bioadhesive gels (NF1-NF5) using Carbopol 940 and studied for the standard in-vitro and ex-vivo characteristics and cytotoxicity potential. The best hydrogel, demonstrated smooth and uniform appearance, pH 6.9 +/- 0.18, content 87.32 +/- 2.72%, spreadability 4.6 +/- 0.19 cm, an equilibrium swelling of 0.745 and pseudo-plastic and thixotropic behavior. The hydrogel sustained the carboplatin release in phosphate buffer saline, pH 7.4 up to 24 h, relative to a fast release of the pure carboplatin solution. The bioadhesion, of hydrogel, measured in weight was 4.75 +/- 0.60 kg. Ex-vivo permeation at 8 h in the receptor media was limited to 3.50 +/- 1.23 mu g/cm2 through goat vaginal mucosal membrane. The in-vitro cytotoxic potential of carboplatin, reflected by IC50 after incubation for 24 h (21.43 +/- 1.30 mu g/ml), was improved compared to the carboplatin nanosponges (35.56 +/- 2.42 mu g/ml) and pure carbo-platin solution (40.53 +/- 2.82 mu g/ml). Thus, the nanosponge in hydrogel, a dual approach for carboplatin held the rationale for achieving sustained release and localized delivery. Hence, the developed system could be proposed as an innovative approach for carboplatin delivery to the cervical cancer by intravaginal administration.