title: Tunable Biodegradable Nanocomposite Hydrogel for Improved Cisplatin Efficacy on HCT-116 Colorectal Cancer Cells and Decreased Toxicity in Rats.
abstract: This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.
authors.affiliation: Department of Pharmaceutics, National Organization of Drug Control and Research , 6 Abou Hazem Street, P.O. Box 29, Pyramids, Egypt.
authors.forename: Hend Mohamed
authors.initials: HM
authors.lastname: Abdel-Bar
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University , Cairo, Egypt.
authors.forename: Rihab
authors.initials: R
authors.lastname: Osman
authors.affiliation: Department of Pharmaceutics, National Organization of Drug Control and Research , 6 Abou Hazem Street, P.O. Box 29, Pyramids, Egypt.
authors.forename: Amal Youssef
authors.initials: AY
authors.lastname: Abdel-Reheem
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University , Cairo, Egypt.
authors.forename: Nahed
authors.initials: N
authors.lastname: Mortada
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University , Cairo, Egypt.
authors.forename: Gehanne A S
authors.initials: GA
authors.lastname: Awad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity; D015179:Colorectal Neoplasms; D004337:Drug Carriers / Q000008:administration & dosage* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D053761:Nanocomposites / Q000008:administration & dosage* / Q000633:toxicity; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D020100:Hydrogels; D002945:Cisplatin