Evaluation of Chitosan-Methotrexate Nanoparticles Loaded in Alginate Beads for Controlled Drug Delivery Against Breast Cancer

To achieve desired local or systemic effects, controlled drug delivery systems release therapeutic agents at a predetermined rate. For controlled drug delivery, chitosan-based methotrexate (MTX) nanoparticles encapsulated within alginate beads were developed and evaluated. Although methotrexate is widely used in breast cancer chemotherapy, its clinical utility is limited by its severe side effects. In this study, Methotrexate was loaded into chitosan nanoparticles (CS-MTX-NPs) via ionic-gelation technique, using tripolyphosphate (TPP) as cross-linker. The optimized nanoparticle was embedded into alginate beads. A variety of physicochemical properties of the nanoparticles and beads were evaluated, including particle size, shape, surface morphology, zeta potential, entrapment efficiency, drug content, swelling index, in vitro release, pharmacokinetic profile and percentage cell toxicity. According to the ATR-FTIR spectroscopy study, pure methotrexate (MTX), formulation excipients, and polymers were compatible with each other. The prepared nanoparticles have sizes ranging from 265 to 370 nm, zeta potentials of 32 to 44 mV, maximum drug content of 85.05%, and entrapment efficiency of 81.06%. Formulation NP4 having 1% chitosan shows favorable results. 90% of drug was released in vitro after 24 h from CS-MTX-NPs. The prepared CS-MTX-NPs loaded alginate beads have an acceptable bead size of 1.34 mm, drug content of 71.61%, entrapment efficiency of 94.22%, and swelling index of 66–81% at pH 1.2, 264–279% at pH 6.8, and 292–307% at pH 7.4. The effects of pH 1.2, 6.8, and 7.4 on the release profile of the drug from CS-MTX-NPs loaded beads were investigated in vitro. Approximately 90% of MTX was released within 24 h. Formulation BD4 showed controlled release behavior compared to other formulations due to higher % of alginate. As evidenced by the results of the cell viability test against the MCF-7 (ATCC HTB-22TM) human breast cancer cell line, optimized NP4 demonstrated enhanced tumor inhibition capability. Based on comparisons with MTX and CS-MTX-NPs, the chitosan nanoparticle embedded beads displayed a higher Cmax and AUC. It was concluded that CS-MTX-NPs loaded alginate beads may be potentially promising oral controlled release carriers for MTX against breast cancer, representing a novel approach by combining chitosan nanoparticles with alginate beads for enhanced efficacy and controlled release.