Precipitation casting of drug-loaded microporous PCL matrices: incorporation of progesterone by co-dissolution.
Microporous, poly(epsilon-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 degrees 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 microg/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 degrees 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.
Aston Pharmacy School, Aston University, Birmingham, B4 7ET, UK.
H-I
HI
Chang
M R
MR
Williamson
Y
Y
Perrie
A G A
AG
Coombes
D000818:Animals; D011232:Chemical Precipitation; D016503:Drug Delivery Systems; D051379:Mice; D011091:Polyesters / Q000008:administration & dosage*; D011374:Progesterone / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility
D011091:Polyesters; C016240:polycaprolactone; D011374:Progesterone