title: The influence of modified pluronic F127 copolymers with higher phase transition temperature on arsenic trioxide-releasing properties and toxicity in a subcutaneous model of rats.
abstract: Pluronic F127 (PF-127) shows thermoreversible property, which is of the utmost interest in optimizing drug formulation and delivery. However, its hitherto unresolved drawback of a low phase transition temperature (T                         (tr)) has limited its application in injectable drug delivery systems. We have recently synthesized a new type of PF-127 copolymers with higher T                         (tr) using a simple oxidative method. Here, we have investigated the drug-releasing feature of oxidized PF-127 and oxidized PF-127-containing silver nanoparticles (SNPs), carrying arsenic trioxide (ATO), in a subcutaneous model of rats. Injectable hydrogels prepared with oxidized PF-127s were less viscous and easier to inject, at the same concentration, than their precursor. Addition of SNPs further elevated T                         (tr), resulting in even lower viscosity of the injectable hydrogel prepared from SNP-containing oxidized PF-127. The oxidized PF-127 copolymers did not differ significantly in ATO-releasing ability, compared with parental PF-127, but the addition of SNPs altered the ATO-releasing feature of oxidized PF-127 to some extent. ATO-carrying oxidized PF-127s had similar toxicity, but the addition of SNPs enhanced the hepatotoxicity of ATO, as evidenced by elevated serum levels of alanine aminotransferase and aspartate aminotransferase and histological alterations, compared to parental PF-127. The results presented herein warrant further investigation of the modified PF-127 copolymers to deliver ATO or other drugs in the form of injectable hydrogels.
authors.affiliation: The Hepatosplenic Surgery Center, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Chen
authors.forename: Hongchi
authors.initials: H
authors.lastname: Jiang
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Easteal
authors.forename: Xueying
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006321:Heart / Q000187:drug effects; D020100:Hydrogels; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053768:Metal Nanoparticles; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D010087:Oxides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D020442:Poloxamer / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D012834:Silver / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D015415:Biomarkers; D004337:Drug Carriers; D020100:Hydrogels; D010087:Oxides; D020442:Poloxamer; D012834:Silver; D000077237:Arsenic Trioxide