Enhanced delivery of Dacarbazine using Nanosponge loaded Hydrogel for Targeted Melanoma Treatment: Formulation, Statistical Optimization and Pre-clinical Evaluation

Abstract

Purpose

Conventional cancer treatments often possess systemic side effects, limiting their efficacy. Nanosponges present a promising solution for targeted drug delivery, allowing precise release of encapsulated drugs and enhanced bioavailability.

Methods

Using a statistical design approach (Box- Behnken design), the nanosponges were optimized to achieve controlled particle size and drug % EE. The optimized formulation (DZ-NS 4) was incorporated into a hydrogel base using HPMC to enable controlled drug delivery. In-vitro, in-vivo, and ex-vivo characterisations were performed to assess drug release, skin permeation and biocompatibility.

Results

The optimized DZ nanosponges showed controlled particle size (338.6 nm) and high entrapment efficiency (92.2%). Subsequent in-vitro characterization of DZ nanosponge hydrogel demonstrated sustained drug release (82% over 12 h), and ex-vivo showed effective skin permeation (73% through sheep skin), and good in-vivo biocompatibility showing minimal signs of skin reactions. The optimized formulation exhibited substantial anti-proliferative activity, with an IC₅₀ value of 68.81 µg/mL, compared to the standard cisplatin, which had an IC₅₀ value of 6022.0 µg/mL, indicating superior inhibition of melanoma cell proliferation.

Conclusion-

Taken together, this study successfully designed a novel Dacarbazine nanosponges hydrogel with promising topical therapeutic option for Melanoma treatment, offering targeted delivery, sustained therapeutic effects, and minimal systemic side effects.

Graphical Abstract