title: In vivo pharmacokinetics, biodistribution and the anti-tumor effect of cyclic RGD-modified doxorubicin-loaded polymers in tumor-bearing mice.
abstract: In our previous study, we successfully produced and characterized a multifunctional drug delivery system with doxorubicin (RC/GO/DOX), which was based on graphene oxide (GO) and cyclic RGD-modified chitosan (RC). Its characteristics include: pH-responsiveness, active targeting of hepatocarcinoma cells, and efficient loading with controlled drug release. Here, we report the pharmacokinetics, biodistribution, and anti-tumor efficacy of RC/GO/DOX polymers in tumor-bearing nude mice. The objective of this study is to assess its targeting potential for tumors. Pharmacokinetic and biodistribution profiles demonstrated that tumor accumulation of RC/GO/DOX polymers was almost three times higher than the others, highlighting the efficacy of the active targeting strategy. Furthermore, the tumor inhibition rate of RC/GO/DOX polymers was 56.64%, 2.09 and 2.93 times higher than that of CS/GO/DOX polymers (without modification) and the DOX solution, respectively. Anti-tumor efficacy results indicated that the tumor growth was better controlled by RC/GO/DOX polymers than the others. Hematoxylin and eosin (H&E) staining showed remarkable changes in tumor histology. Compared with the saline group, the tumor section from the RC/GO/DOX group revealed a marked increase in the quantity of apoptotic and necrotic cells, and a reduction in the quantity of the blood vessels. Together, these studies show that this new system could be regarded as a suitable form of DOX-based treatment of the hepatocellular carcinoma.
authors.affiliation: School of Pharmacy, Xiamen Medical College, Xiamen 361008, PR China. Electronic address: Fjxmstorm@163.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Xiamen Medical College, Xiamen 361008, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Xiamen Xianyue Hospital, 361012, PR China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010456:Peptides, Cyclic / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D010456:Peptides, Cyclic; D011108:Polymers; C507169:cyclic arginine-glycine-aspartic acid peptide; D004317:Doxorubicin
keywords: Anti-tumor effect; Biodistribution; Cyclic RGD; Graphene oxide; Pharmacokinetics