Engineered\nPLGA Core–Lipid Shell Hybrid Nanocarriers\nImprove the Efficacy and Safety of Irinotecan to Combat Colon Cancer

Poly(lactide-<i>co</i>-glycolide) (PLGA) is\na biocompatible\nand biodegradable copolymer that has gained high acceptance in biomedical\napplications. In the present study, PLGA (<i>M</i><sub>w</sub> = 13,900) was synthesized by ring-opening polymerization in the\npresence of a biocompatible zinc–proline initiator through\na green route. Irinotecan (Ir) loaded with efficient PLGA core–lipid\nshell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine and 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-<i>N</i>-[amino\n(polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin,\nby a nanoprecipitation method, and the fabricated LPs were designated\nas P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were\nfurther validated for their physicochemical properties and biological\npotential for colon cancer application. The potential delivery of\na poorly water-soluble chemotherapeutic drug (Ir) was studied for\nthe treatment of colon cancer. LPs were successfully prepared, providing\ncontrolled size (80–120 nm) and surface charge (∼ −35\nmV), and the sustained release properties and cytotoxicity against\nCT-26 colon cancer cells were studied. The in vivo biodistribution\nand tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice\nshowed promising results for tumor uptake and retention for a prolonged\ntime period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant\ntumor growth delay as compared to untreated and blank formulation-treated\ngroups in CT-26 (subcutaneous tumor model) after 4 treatments of 10\nmg irinotecan/kg dose. The biocompatibility and safety of the LPs\nwere confirmed by an acute toxicity study of the optimized formulation.\nOverall, this proof-of-concept study demonstrates that the PLGA-based\nLPs improve the efficacy and bioavailability and decrease neutropenia\nof Ir to combat colon cancer.