title: Cervical cancer treatment with a locally insertable controlled release delivery system.
abstract: Local delivery of cancer chemotherapeutics enables sustained drug levels at the site of action thereby reducing systemic side effects. A novel insertable polymeric drug delivery system for cervical cancer treatment is presented. Cisplatin, the first line of therapy employed for cervical cancers, was incorporated in a poly(ethylene-co-vinyl acetate) (EVAc) device that is similar to those currently used for vaginal contraceptive delivery. Cisplatin crystals were uniformly dispersed in the polymeric system without undergoing significant dissolution in the polymer matrix. Cisplatin dissolution from the devices was biphasic, consistent with a matrix-type controlled-release system with an initial rapid release phase followed by a slower, near linear release phase. Depending on the drug loading in the polymeric devices, the near-linear release phase varied in rate according to both empirical, linear curve-fitting (0.38+/-0.15 microg/day to 46.9+/-10.0 microg/day) and mechanistic, diffusion analysis based upon diffusion through a porous structure (D(app) from 1.3+/-0.5 x 10(-9) cm2/s to 5.8+/-0.3 x 10(-12) cm2/s). The devices were tested for in vitro activity and found to be effective against both HPV positive and HPV negative cervical cancer cell lines. Preliminary studies indicate that this delivery system would be a good candidate for investigation as a choice of treatment in cervical cancers.
authors.affiliation: The University of Illinois, Department of Biopharmaceutical Sciences, Chicago, IL 60612, USA.
authors.forename: Vandana
authors.initials: V
authors.lastname: Keskar
authors.forename: Prem S
authors.initials: PS
authors.lastname: Mohanty
authors.forename: Ernest J
authors.initials: EJ
authors.lastname: Gemeinhart
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gemeinhart
mesh_terms: D000282:Administration, Intravaginal; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D004343:Drug Implants; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D002945:Cisplatin