Engineered PLGA Core–Lipid Shell Hybrid Nanocarriers Improve the Efficacy and Safety of Irinotecan to Combat Colon Cancer

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 g...

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Veröffentlicht in:ACS biomaterials science & engineering 2024-10, Vol.10 (10), p.6661-6676
Hauptverfasser: Giram, Prabhanjan S., Nimma, Ramakrishna, Bulbule, Anuradha, Yadav, Amit Singh, Gorain, Mahadeo, Venkata Radharani, Nalukurthi Naga, Kundu, Gopal C., Garnaik, Baijayantimala
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Sprache:eng
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Zusammenfassung: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.
ISSN:2373-9878
2373-9878
DOI:10.1021/acsbiomaterials.4c01260