Shikha Dhiman, Amardeep Kaur, G L Gupta, Manu Sharma
{"title":"生物素功能化富勒烯用于伊立替康结肠肿瘤递送的开发与评价。","authors":"Shikha Dhiman, Amardeep Kaur, G L Gupta, Manu Sharma","doi":"10.2174/1567201819666220516153010","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy.</p><p><strong>Objective: </strong>The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex.</p><p><strong>Methods: </strong>Fullerene (C<sub>60</sub>) has been observed as a potential drug delivery agent and the aminefunctionalized C<sub>60</sub>-NH<sub>2</sub> was synthesized by functionalizing ethylenediamine on the surface of C<sub>60</sub>. The PEI functionalized C<sub>60</sub> was further synthesized by polymerization of aziridine on the surface of C<sub>60</sub>- NH2. Biotin was attached by an amide linkage to C<sub>60</sub>-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C<sub>60</sub>-PEI-Biotin/IRI). The C<sub>60</sub>-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan.</p><p><strong>Results: </strong>The results showed that C<sub>60</sub>-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan.</p><p><strong>Conclusion: </strong>It is hypothesized that the conjugate (C<sub>60</sub>-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":"20 7","pages":"978-991"},"PeriodicalIF":2.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development and Evaluation of Biotin Functionalized Fullerenes for the Delivery of Irinotecan to Colon Tumors.\",\"authors\":\"Shikha Dhiman, Amardeep Kaur, G L Gupta, Manu Sharma\",\"doi\":\"10.2174/1567201819666220516153010\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy.</p><p><strong>Objective: </strong>The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex.</p><p><strong>Methods: </strong>Fullerene (C<sub>60</sub>) has been observed as a potential drug delivery agent and the aminefunctionalized C<sub>60</sub>-NH<sub>2</sub> was synthesized by functionalizing ethylenediamine on the surface of C<sub>60</sub>. The PEI functionalized C<sub>60</sub> was further synthesized by polymerization of aziridine on the surface of C<sub>60</sub>- NH2. Biotin was attached by an amide linkage to C<sub>60</sub>-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C<sub>60</sub>-PEI-Biotin/IRI). The C<sub>60</sub>-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan.</p><p><strong>Results: </strong>The results showed that C<sub>60</sub>-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. 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Development and Evaluation of Biotin Functionalized Fullerenes for the Delivery of Irinotecan to Colon Tumors.
Background: Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy.
Objective: The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex.
Methods: Fullerene (C60) has been observed as a potential drug delivery agent and the aminefunctionalized C60-NH2 was synthesized by functionalizing ethylenediamine on the surface of C60. The PEI functionalized C60 was further synthesized by polymerization of aziridine on the surface of C60- NH2. Biotin was attached by an amide linkage to C60-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C60-PEI-Biotin/IRI). The C60-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan.
Results: The results showed that C60-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan.
Conclusion: It is hypothesized that the conjugate (C60-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.
期刊介绍：
Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves.
The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.
The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.
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