Polymeric complex nanocarriers of Mangifera indicagum & chitosan for methotrexate delivery: Formulation, characterization, and in vitro toxicological assessment

Methotrexate (MTX), a widely used chemotherapeutic drug, exhibits significant potential in the treatment of various solid tumors and hematologic malignancies. However, its therapeutic efficacy is often hampered by suboptimal pharmacokinetic profiles, causing drug resistance and a shortened plasma half-life. In recent years, in light of these challenges, a demand has arisen for novel strategies to augment the therapeutic potential of methotrexate. The present study presents an innovative approach in the development and evaluation of non-toxic nanocarriers designed for methotrexate delivery, using a biopolymer matrix comprised of Mangifera Indicagum (MIG) and chitosan (CS), employing the coacervation technique. The optimization process, guided by central composite design, was utilized to attain an optimal formulation containing 0.02% w/v% MIG and 0.01% w/v% CS. The characterization of optimized formulation revealed smooth, spherical nanoparticles (229.7 nm diameter, PDI 0.296) with 69.5 ± 2.0% entrapment efficiency. Additionally, a pH-dependent sustained release of the MTX for up to 24 h was found using in-vitro drug release analysis. Furthermore, the optimized formulation displayed significant cytotoxic effects in an MTT assay, highlighting its potential as an effective carrier for the delivery MTX to cancer cells. These findings offer valuable insights into pH-responsive drug delivery to tumor cells and underscore the promising therapeutic efficacy of MIG/CS nanoparticles, positioning them as a compelling option for novel pharmaceutical formulations.