Tamarind/β-CD-g-poly (MAA) pH responsive hydrogels for controlled delivery of Capecitabine: fabrication, characterization, toxicological and pharmacokinetic evaluation
Abstract The present study was aimed for controlled delivery of capecitabine, an anticancer drug used to treat colorectal cancer. Smart pH responsive tamarind/-CD-g-poly (MAA) hydrogels were developed using the free radical polymerization process to overcome the constraints of capecitabine such as short plasma half-life, low bioavailability, and high dose frequency. The developed network system was evaluated for different characterizations including equilibrium swelling (%), drug loading efficiency (%), thermal behavior, elemental composition, morphology, complexation of components and release kinetics. Furthermore, safety profile of developed network was validated by acute oral toxicity studies and pharmacokinetic parameters were determined by carrying in-vivo studies in healthy rabbits. The grafted system proved to be thermally stable as confirmed by DSC and TGA analysis. While successful grafting, compatibility of hydrogel components and amorphous dispersion of drug within the network were shown by FTIR analysis and XRD studies. Significantly higher swelling and drug release were observed at pH 7.4 than at pH 1.2, evidencing pH responsive character of hydrogels. Maximum drug release of 94.3% was shown over period of 30 h demonstrating the controlled release profile of polymeric network. Toxicity evaluations revealed good safety profile and biocompatibility of hydrogels. Moreover, in-vivo studies showed sustained release profile of capecitabine as proved by significant increase in its half-life (13 h) and AUC (42.88 µg.h/ml) when administered as hydrogels. Hence, tamarind/β-CD-g-poly (MAA) hydrogels are strongly recommended to be employed as biocompatible pH responsive carrier system and can be utilized for controlled and targeted delivery of drugs..
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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Enthalten in: |
Journal of polymer research - 30(2022), 1 vom: 29. Dez. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Rehman, Umaira [VerfasserIn] |
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Links: |
Volltext [lizenzpflichtig] |
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Themen: |
Controlled delivery |
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Anmerkungen: |
© The Polymer Society, Taipei 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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doi: |
10.1007/s10965-022-03422-7 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
SPR048945064 |
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520 | |a Abstract The present study was aimed for controlled delivery of capecitabine, an anticancer drug used to treat colorectal cancer. Smart pH responsive tamarind/-CD-g-poly (MAA) hydrogels were developed using the free radical polymerization process to overcome the constraints of capecitabine such as short plasma half-life, low bioavailability, and high dose frequency. The developed network system was evaluated for different characterizations including equilibrium swelling (%), drug loading efficiency (%), thermal behavior, elemental composition, morphology, complexation of components and release kinetics. Furthermore, safety profile of developed network was validated by acute oral toxicity studies and pharmacokinetic parameters were determined by carrying in-vivo studies in healthy rabbits. The grafted system proved to be thermally stable as confirmed by DSC and TGA analysis. While successful grafting, compatibility of hydrogel components and amorphous dispersion of drug within the network were shown by FTIR analysis and XRD studies. Significantly higher swelling and drug release were observed at pH 7.4 than at pH 1.2, evidencing pH responsive character of hydrogels. Maximum drug release of 94.3% was shown over period of 30 h demonstrating the controlled release profile of polymeric network. Toxicity evaluations revealed good safety profile and biocompatibility of hydrogels. Moreover, in-vivo studies showed sustained release profile of capecitabine as proved by significant increase in its half-life (13 h) and AUC (42.88 µg.h/ml) when administered as hydrogels. Hence, tamarind/β-CD-g-poly (MAA) hydrogels are strongly recommended to be employed as biocompatible pH responsive carrier system and can be utilized for controlled and targeted delivery of drugs. | ||
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