Engineered PLGA Core–Lipid Shell Hybrid Nanocarriers Improve the Efficacy and Safety of Irinotecan to Combat Colon Cancer
Prabhanjan Giram, Ramakrishna Nimma, Anuradha Bulbule, Amit Singh Yadav, Mahadeo Gorain, Nalukurthi Naga Venkata Radharani, Gopal C. Kundu, Baijayantimala Garnaik
Abstract
Poly(lactide- co -glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA ( M w = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc–proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core–lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl- sn -glycero-3-phosphoethanolamine and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80–120 nm) and surface charge (∼ −35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.