title: Comparison of drug release from poly(lactide-co-glycolide) microspheres and novel fibre formulations.
abstract: Intraperitoneal cisplatin delivery has recently been shown to benefit ovarian cancer patients. Cisplatin-containing poly(lactide-co-glycolide) (PLGA) microspheres have been proposed for cisplatin delivery. The drug loading of cisplatin containing microspheres produced elsewhere is 3-10%w. Similar microspheres are reported here with a mean diameter of 38.8 µm, and a drug loading of 11.7%w, but using ethyl acetate as a safer solvent. In addition, novel formulations of cisplatin-containing solid and hollow PLGA 65:35 (lactide:glycolide) fibres were prepared and are reported here for the first time. PLGA hollow fibres were produced by phase inversion with a high drug loading of 27%w. Mechanistic mathematical models were applied to the cisplatin release profiles to allow quantitative comparison of microsphere, solid fibre and hollow fibre formulations. The diffusion coefficient of cisplatin eluting from a typical batch of PLGA microspheres was 4.8 × 10(-13) cm(2) s(-1); this low diffusivity of cisplatin in microspheres was caused by the low porosity of the polymer matrix. The diffusion coefficients of cisplatin eluting from a batch of PLGA solid fibres and hollow fibres were 6.1 × 10(-10) and 3.3 × 10(-10) cm(2) s(-1), respectively. These fibres allowed the controlled release of high doses of cisplatin over four days and may represent an improvement in slow release technology for treatment of ovarian cancer.
authors.affiliation: Department of Chemical Engineering, University of Bath, UK.
authors.forename: Christopher S J
authors.initials: CS
authors.lastname: Campbell
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, UK.
authors.forename: M Begoña
authors.initials: MB
authors.lastname: Delgado-Charro
authors.affiliation: Department of Chemical Engineering, University of Bath, UK.
authors.forename: Olivier
authors.initials: O
authors.lastname: Camus
authors.affiliation: Department of Chemical Engineering, University of Bath, UK S.P.Perera@bath.ac.uk.
authors.forename: Semali
authors.initials: S
authors.lastname: Perera
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D065546:Drug Liberation; D008863:Microspheres; D011098:Polyglactin 910 / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D011098:Polyglactin 910; D002945:Cisplatin
keywords: Cisplatin; fibres; intraperitoneal; mathematical model; ovarian cancer; poly(lactide-co-glycolide)