Prabhanjan S. Giram, Ramakrishna Nimma, Anuradha Bulbule, Amit Singh Yadav, Mahadeo Gorain, Nalukurthi Naga Venkata Radharani, Gopal C. Kundu, Baijayantimala Garnaik
{"title":"工程化聚乳酸(PLGA)核脂壳混合纳米载体提高了伊立替康治疗结肠癌的疗效和安全性","authors":"Prabhanjan S. Giram, Ramakrishna Nimma, Anuradha Bulbule, Amit Singh Yadav, Mahadeo Gorain, Nalukurthi Naga Venkata Radharani, Gopal C. Kundu, Baijayantimala Garnaik","doi":"10.1021/acsbiomaterials.4c01260","DOIUrl":null,"url":null,"abstract":"Poly(lactide-<i>co</i>-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (<i>M</i><sub>w</sub> = 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-<i>sn</i>-glycero-3-phosphoethanolamine and 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-<i>N</i>-[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.","PeriodicalId":8,"journal":{"name":"ACS Biomaterials Science & Engineering","volume":null,"pages":null},"PeriodicalIF":5.4000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Engineered PLGA Core–Lipid Shell Hybrid Nanocarriers Improve the Efficacy and Safety of Irinotecan to Combat Colon Cancer\",\"authors\":\"Prabhanjan S. Giram, Ramakrishna Nimma, Anuradha Bulbule, Amit Singh Yadav, Mahadeo Gorain, Nalukurthi Naga Venkata Radharani, Gopal C. Kundu, Baijayantimala Garnaik\",\"doi\":\"10.1021/acsbiomaterials.4c01260\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Poly(lactide-<i>co</i>-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (<i>M</i><sub>w</sub> = 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-<i>sn</i>-glycero-3-phosphoethanolamine and 1,2-distearoyl-<i>sn</i>-glycero-3-phosphoethanolamine-<i>N</i>-[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. 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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 (Mw = 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.
期刊介绍:
ACS Biomaterials Science & Engineering is the leading journal in the field of biomaterials, serving as an international forum for publishing cutting-edge research and innovative ideas on a broad range of topics:
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Characterization, Synthesis, and Modification – new biomaterials, bioinspired and biomimetic approaches to biomaterials, exploiting structural hierarchy and architectural control, combinatorial strategies for biomaterials discovery, genetic biomaterials design, synthetic biology, new composite systems, bionics, polymer synthesis
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