title: Mucoadhesive hybrid gel improves intraperitoneal platinum delivery.
abstract: A leading cause of death and suffering in patients with abdominal or pelvic malignancies is progression of peritoneal surface disease. Changes in the use of chemotherapy have shown significant survival benefits for intraperitoneal or combined intraperitoneal and intravenous treatment following optimal surgical cytoreduction. However, broader clinical use of intraperitoneal therapy has not reached its full potential due to limited efficacy, accessibility and nonspecific toxicity. To overcome these problems, we developed a mucoadhesive hybrid gel (HG) for a local, intraperitoneal drug delivery. In vivo studies confirmed reliable adherence and residence of the gel to the peritoneal sidewall for at least 72 h exhibiting no signs of tissue toxicity. Functionally active CDDP was released from HG within 2h and was equal to free CDDP in vitro. Moreover, intraperitoneal application of HG-CDDP significantly enhanced CDDP accumulation in the genomic DNA of peritoneal tissues compared to the same CDDP dose administered intravenously. These findings indicate the potential application of this hybrid gel as a mucoadhesive drug carrier amendable to use for intraperitoneal drug delivery and possible expansion for use on other mucosal surfaces of the female reproductive tract.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah, Salt Lake City, UT 84132, USA.
authors.forename: Sungpil
authors.initials: S
authors.lastname: Cho
authors.forename: Yongen
authors.initials: Y
authors.lastname: Sun
authors.forename: Elke A
authors.initials: EA
authors.lastname: Jarboe
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Soisson
authors.forename: Mark K
authors.initials: MK
authors.lastname: Dodson
authors.forename: David K
authors.initials: DK
authors.lastname: Gaffney
authors.forename: C Matthew
authors.initials: CM
authors.lastname: Peterson
authors.forename: Margit M
authors.initials: MM
authors.lastname: Janát-Amsbury
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006367:HeLa Cells; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007274:Injections, Intraperitoneal / Q000379:methods*; D051379:Mice; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry; D010537:Peritoneum / Q000378:metabolism*
chemical_list: D000464:Alginates; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D009944:Organoplatinum Compounds; D020723:Glucuronic Acid; D004247:DNA; D002945:Cisplatin
keywords: Chitosan; Hybrid gel; Intraperitoneal delivery; Mucoadhesion; cis-Diaminedichloroplatinum (II) (CDDP)