Chitosan Nanoparticles of Paclitaxel for the Treatment against MDA-MB-231 Breast Cancer Cells via Oral Nanomedicine: Fabrication and Preclinical Assessment

Background: Taxanes have demonstrated and established efficacy against various forms of cancer, with a particular emphasis on breast cancer. Unfortunately, the strong hydrophobicity and severe hemolytic toxicity of paclitaxel and docetaxel have always made it hard to administer them safely and effectively. Utilizing biodegradable materials in conjunction with the benefits of nanotechnology may be able to enhance the situation in order to accomplish more secure and effective delivery. The study aimed to assess how well chitosan nanoparticles loaded with crosslinked paclitaxel destroy breast cancer cells by identifying the changes to their surface and the shape of the particles. Method: Utilizing an elementary spray-drying method, paclitaxel-loaded chitosan nanoparticles were developed and refined in the current investigation. Moreover, employing the Box-Behnken design to examine the impact of different formulation variables on the nanoparticles that were prepared. Chitosan nanoparticles laden with paclitaxel were synthesized via ionic gelation and spray drying. Results: The batch PCT-CNPs5 had particles that were 189.35±2.54 nm in size and had a maximum loading capacity of 75.34±0.36% and an entrapment efficiency of 79.35±0.85%. An analysis of variance (ANOVA) was executed to examine the fit and significance of the model with respect to particle size, entrapment efficiency, and percent cumulative drug release. After 24 hours, the PCT-CNPs-5 batch exhibited drug release rates of 45.62% in phosphate buffer (pH 6.8) and 86.95% in 0.1N HCl. An additional dimension assessment of the nanoparticles was conducted using transmission electron microscopy. The MTT assay demonstrated an increase in in vitro anticancer activity when applied to MDA-MB-231 breast cancer cell lines that are triple negative. The IC50 values for PCT-CNPs-5 were 12.37±1.26 μM, which is about 1.284 times (p <0.05) less than the IC50 values of the pure drug. Comparatively, the hemolytic toxicity of PCT-CNPs-5 was nearly 3,841-fold lower (p ≥0.05) than that of the control drug, indicating that PCT-CNPs-5 were exceptionally safe and biocompatible. Using flow cytometry to measure apoptosis, the anticancer activity was further assessed. A study on cell apoptosis found that PCT-CNPs-5 treatment increased late cell apoptosis by almost two times compared to naïve paclitaxel. Conclusion: It was observed that the synthesized and optimized nanoparticles exhibited in vitro activity against cancer cells. As a consequence, not only did the developed formulation decrease the overall toxicity of paclitaxel, but it also enhanced its anticancer activity. Based on the developed, characterized, and evaluated Paclitaxel's nanoformulation, it may be inferred that it is persistent, robust, and relatively safe.