Rapidly evolving drug delivery systems employ therapeutic agents (liposomes, polymers, and nanospheres) to achieve optimum therapeutic and targeted effects with declined side effects to cure chronic diseases like cancer. Nano-formulation of a natural product i.e., Caralluma tuberculata (Ct) extract, has been used as an effective combinational therapy with enhanced biocompatibility owing to its strong anti-oxidant, anti-inflammatory, anti-bacterial, and anti-tumor potential. Ct extract was prepared using three solvents (EtOH, MeOH, and CHCl3) amongst which methanolic Ct extract exhibited the highest percentage yield (9.6%). Qualitative phytochemical screening, thin layer chromatography (TLC), and antioxidant assays (DPPH assay and H2O2 assay) were performed. The percentage free radical scavenging values were found to be 86.25% (IC50=140.1μg/ml) and 88% (IC50=14.22μg/ml) at 1000 μg/ml concentration for both assays respectively. Methanolic Ct extract was then encapsulated in chitosan-tripolyphosphate (CS-TPP) nanoparticles using ionic gelation method with an encapsulation efficiency of 87%. Characterization showed uniform size distribution of 140nm particle size using DLS and encapsulation of Ct extract inside CS-TPP nanoparticles was confirmed by UV spectrophotometry and FTIR. Ct loaded CS-TPP nanoparticles showed less than or equal to 5% hemolytic activity at concentrations of 15.62μg/ml, 31.25μg/ml, 62.5μg/ml, and 125μg/ml, suggesting its safer usage at lower concentration. Rhodamine conjugated Ct loaded CS-TPP nanoparticles showed significant uptake efficiency in breast cancer cells compared to control. Ct extract and the nanoformulation were treated against triple negative breast cancer cell lines (Cal-51) for the evaluation of cytotoxicity exhibiting 30-40% (IC50=122.3μg/ml) and up to 75% (IC50=14.39μg/ml) cytotoxicity respectively. The study paves way for the encapsulation of medicinal plants in polymeric nanoparticles to achieve safer and highly efficient drug delivery systems
