Hyaluronic acid functionalized liposomes embedded in biodegradable beads for duo drugs delivery to oxaliplatin-resistant colon cancer

Oxaliplatin (OHP) resistance is a major hurdle in the chemotherapeutic treatment of colorectal cancer (CRC). The present study aimed to formulate Eudragit S-100 (ES-100) coated alginate beads bearing drugs loaded targeted liposomes for simultaneous delivery of OHP and curcumin (CUR) to exert a synergistic therapeutic effect on OHP- resistant HT-29 cell line. The liposomes were prepared by the thin-film hydration method and optimized for various formulation parameters using a Box-Behnken design (BBD) with the aid of Design-Expert® software. Hyaluronic acid (HA) was conjugated on the liposomal surface using carbodiimide chemistry to target CD44 receptors, which are overexpressed on the CRC cells. HA coupled drugs bearing liposomes (OC-L-HA) were then characterized for various attributes, viz. shape, surface-morphology, size, zeta potential, PDI, entrapment efficiency, and drug loading, as well as in-vitro cell-based studies. OC-L-HA were entrapped in the alginate beads and examined for their in vitro potential and in vivo performances. MTT assay demonstrated that OC-L-HA exhibited 2.76 and 2.58 fold higher cytotoxicity than targeted CUR liposomes and targeted OHP liposomes, respectively. The in vivo X-ray images affirmed the good targeting ability of the targeted beads to the colon. The outcomes of the studies revealed that these surface-modified liposomes entrapped in Eudragit S-100 coated beads could be an effective strategy for the treatment of CRC. [Display omitted]