title: Intraperitoneal chemotherapy of ovarian cancer by hydrogel depot of paclitaxel nanocrystals.
abstract: Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of ovarian cancer, but the full potential is yet to be realized. To facilitate IP chemotherapy of ovarian cancer, we developed an in-situ crosslinkable hydrogel depot containing paclitaxel (PTX) nanocrystals (PNC). PNC suppressed SKOV3 cell proliferation more efficiently than microparticulate PTX precipitates (PPT), and the gel containing PNC (PNC-gel) showed a lower maximum tolerated dose than PPT-containing gel (PPT-gel) in mice, indicating greater dissolution and cellular uptake of PNC than PPT. A single IP administration of PNC-gel extended the survival of tumor-bearing mice significantly better than Taxol, but PPT-gel did not. These results support the advantage of PNC over PPT and demonstrate the promise of a gel depot as an IP drug delivery system.
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 Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Maie S
authors.initials: MS
authors.lastname: Taha
authors.affiliation: Biological Evaluation Shared Resource, Purdue University Center for Cancer Research, 201 S. University Street, West Lafayette, IN 47907, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ramsey
authors.affiliation: Biological Evaluation Shared Resource, Purdue University Center for Cancer Research, 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 Center for Cancer Research, 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; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D007274:Injections, Intraperitoneal; D020714:Maximum Tolerated Dose; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D020100:Hydrogels; D017239:Paclitaxel
keywords: Drug delivery; Hydrogel depot; Intraperitoneal chemotherapy; Nanocrystals; Ovarian cancer