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Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation

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Margalla College of Pharmacy, Margalla Institute of Health Sciences, Rawalpindi 46000, Punjab, Pakistan
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College of Pharmacy, University of Sargodha, Sargodha 40100, Punjab, Pakistan
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Department of Pharmacy, University of Malakand, Chakdara 18800, Khyber Pakhtunkhwa, Pakistan
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Discipline of Pharmaceutical Sciences, School of Health Sciences, UKZN, Durban 4041, South Africa
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Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
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Division of Molecular Pharmaceutics and Drug Delivery, Department of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA
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Authors to whom correspondence should be addressed.
Academic Editor: Franco Dosio
Pharmaceutics 2022, 14(5), 1050; https://doi.org/10.3390/pharmaceutics14051050
Received: 14 February 2022 / Revised: 23 March 2022 / Accepted: 25 March 2022 / Published: 13 May 2022
This study was aimed to develop novel in situ forming gels based on N-vinylcaprolactam, sodium alginate, and N,N-methylenebisacrylamide. The in situ Poly (NVRCL-g-NaAlg) gels were developed using the cold and free radical polymerization method. The structure formation, thermal stability, and porous nature of gels was confirmed by FTIR, NMR, DSC, TGA, and SEM. The tunable gelation temperature was evaluated by tube titling and rheological analysis. Optical transmittance showed that all formulations demonstrated phase transition around 33 °C. The swelling and release profile showed that gels offered maximum swelling and controlled 5-FU release at 25 °C and pH (7.4), owing to a relaxed state. Porosity and mesh size showed an effect on swelling and drug release. The in vitro degradation profile demonstrated a controlled degradation rate. An MTT assay confirmed that formulations are safe tested against Vero cells. In vitro cytotoxicity showed that 5-FU loaded gels have controlled cytotoxic potential against HeLa and MCF-7 cells (IC50 = 39.91 µg/mL and 46.82 µg/mL) compared to free 5-FU (IC50 = 50.52 µg/mL and 53.58 µg/mL). Histopathological study demonstrated no harmful effects of gels on major organs. The in vivo bioavailability in rabbits showed a controlled release in gel form (Cmax, 1433.59 ± 45.09 ng/mL) compared to a free drug (Cmax, 2263.31 ± 13.36 ng/mL) after the subcutaneous injection. View Full-Text
Keywords: chemical grafting; N-(vinylcaprolactam); hydrogels; sodium alginate; 5-FU in situ depot; rheology; MTT assay; pharmacokinetics; anticancer drugs chemical grafting; N-(vinylcaprolactam); hydrogels; sodium alginate; 5-FU in situ depot; rheology; MTT assay; pharmacokinetics; anticancer drugs
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MDPI and ACS Style

Khan, S.; Minhas, M.U.; Aqeel, M.T.; Shah, I.; Khan, S.; Kazi, M.; Warnken, Z.N. Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation. Pharmaceutics 2022, 14, 1050. https://doi.org/10.3390/pharmaceutics14051050

AMA Style

Khan S, Minhas MU, Aqeel MT, Shah I, Khan S, Kazi M, Warnken ZN. Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation. Pharmaceutics. 2022; 14(5):1050. https://doi.org/10.3390/pharmaceutics14051050

Chicago/Turabian Style

Khan, Samiullah, Muhammad U. Minhas, Muhammad T. Aqeel, Ihsan Shah, Shahzeb Khan, Mohsin Kazi, and Zachary N. Warnken. 2022. "Poly (N-Vinylcaprolactam-Grafted-Sodium Alginate) Based Injectable pH/Thermo Responsive In Situ Forming Depot Hydrogels for Prolonged Controlled Anticancer Drug Delivery; In Vitro, In Vivo Characterization and Toxicity Evaluation" Pharmaceutics 14, no. 5: 1050. https://doi.org/10.3390/pharmaceutics14051050

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