title: Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.
abstract: Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Cho
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Department of Physiology, College of Medicine, Yeungnam University, 317-1 Daemyung-dong, Daegu, Republic of Korea.
authors.forename: Kyung-Oh
authors.initials: KO
authors.lastname: Doh
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Wilson
authors.affiliation: Biological Evaluation Shared Resource, Purdue University, 201 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Torregrosa-Allen
authors.affiliation: Biological Evaluation Shared Resource, Purdue University, 201 S. University Street, West Lafayette, IN 47907, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Bennett D
authors.initials: BD
authors.lastname: Elzey
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA. Electronic address: yyeo@purdue.edu.
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D005782:Gels / Q000737:chemistry*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D049449:Luminescence; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010984:Platinum / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D005782:Gels; D018960:Hyaluronan Receptors; D010984:Platinum; D006820:Hyaluronic Acid; D002945:Cisplatin
keywords: Drug delivery; Empty carriers; Hyaluronic acid; Intraperitoneal chemotherapy; Ovarian cancer; Platinum