Synthesis of supramolecular nanoparticles for docetaxel using sulfobutyl ether cyclodextrin with improved therapeutic efficacy in breast cancer

Docetaxel (DTX) has limited therapeutic efficacy due to its poor water solubility and intestinal permeability. To improve DTX therapeutic effect, we aimed to design supramolecular nanoparticles (SNPs) of DTX and sulfobutylether-β-cyclodextrin (SBE 7 -β-CD). SNPs were finally synthesized by incorporation of DTX-SBE 7 -β-CD inclusion complexes in nanoparticulate structure of chitosan ionically crosslinked with sodium tri polyphosphate (STPP). Supramolecular nanoparticles (SNPs) showed particle size (372 ± 126.9 nm) with low polydispersity index and narrow size distribution possessing positive zeta potential (19.9 ± 6.66 mV). H 1 NMR revealed DTX is complexed with SBE 7 -β-CD with non-covalent bonding. DTX-SBE 7 -β-CD loaded nanoparticles gave maximum increase in drug loading and encapsulation efficiency (500 ± 0.01 µg/mg, 82.95 ± 0.15 %), respectively. Drug release followed fickian diffusion mechanism with negligible release at acidic pH and higher release at basic pH. Further, significant increase in AUC, C max , and T max was observed with SNPs than oral administered DTX. SNPs administered to healthy rabbits for toxicity evaluation in major organs showed reversible changes in kidney tissues along absence of severe toxicity in heart and liver tissues. SNPs significantly increased cytotoxic activity in MDA-MD-231 cancer cell lines. Hence, our work demonstrated SNPs are suitable for oral delivery of DTX with maximum therapeutic outcomes.