Comparison of drug release from poly(lactide-co-glycolide) microspheres and novel fibre formulations

J Biomater Appl. 2016 Mar;30(8):1142-53. doi: 10.1177/0885328215617327. Epub 2015 Nov 29.

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.

Keywords: Cisplatin; fibres; intraperitoneal; mathematical model; ovarian cancer; poly(lactide-co-glycolide).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Cisplatin / administration & dosage*
  • Cisplatin / chemistry
  • Delayed-Action Preparations / chemistry*
  • Diffusion
  • Drug Liberation
  • Microspheres
  • Polyglactin 910 / chemistry*

Substances

  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Polyglactin 910
  • Cisplatin