Chitosan based copolymer-drug conjugate and its protein targeted polyelectrolyte complex nanoparticles to enhance the efficiency and specificity of low potency anticancer agent

Abstract The effective delivery of low potency anticancer drug is a major challenge. The present study introduces the novel chitosan-polylactic acid (CS-PLA)-drug conjugate and its transferrin receptor targeted polyelectrolyte complex nanoparticles (PEC Nps), encapsulating free drug to increase its potency and specificity. The model drug curcumin (CR) was used and incorporated in this system in both conjugated and encapsulated form. The synthesis of CS-PLA-CR copolymer was confirmed by 1 H NMR, FTIR, UV–visible spectrum, DSC thermogram and zeta potential. Further, the nanoparticles engulfing free CR, with average 340 nm particle sizes, were prepared through simple ionic gelation technique utilizing positive charges on copolymer by polyanion sodium alginate (CS-PLA-CR/SA PEC Nps). The prepared Nps showed the high CR content of over 92% with extended period of CR release (60% and 85% at pH 7.4 and 5 respectively even after 8 days). The results were compared with the unmodified CS (without PLA) as a control to understand the effect of PLA side chain. Transferrin (Tf) conjugation on PEC Nps displayed superior cytotoxicity and cellular uptake compared to non-targeted Nps on MCF-7 cell line. Thus, CR loaded Tf-CS-PLA-CR/SA PEC Nps may provide an efficient and targeted delivery for cancer treatment.