Precipitation casting of drug-loaded microporous PCL matrices: incorporation of progesterone by co-dissolution

H.-I. Chang, M.R. Williamson, Yvonne Perrie, Allan G.A. Coombes

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Abstract

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37 °C over 10 days could be described effectively by a diffusional release model although the Korsmeyer–Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 μg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%–95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37 °C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.
Original languageEnglish
Pages (from-to)263-272
Number of pages10
JournalJournal of Controlled Release
Volume106
Issue number3
DOIs
Publication statusPublished - 1 Sep 2005

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Keywords

  • poly(ε-caprolactone)
  • microporous
  • matrix
  • progesterone
  • MCF-7 cells

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