Evaluation of new pasty-type implantable devices consisting of poly(epsilon-caprolactone/delta-valerolactone) and Estracyt or estramustine.
Biodegradable pasty-type copolyesters with a relatively low molecular weight of 4500 were synthesized by direct copolycondensation of epsilon-caprolactone (CL) and delta-valerolactone (VL) in the absence of catalysts to evaluate in vivo capabilities of the polymer for implantable controlled release devices in drug delivery systems. The devices in cylindrical shape were prepared by the melt-pressing technique using pasty-type copoly(CL/VL) with 53 mol% CL unit, in which Estracyt and estramustine were used as a water soluble and insoluble drug, respectively. The degradation and drug release in vivo of the devices were examined by subcutaneous implantation in the backs of male rats. The degradation of the device was remarkably accelerated by the presence of hydrophilic Estracyt, and was slightly suppressed by hydrohobic estramustine. The estramustine release profile roughly corresponded to the polymer degradation one. It was found that the degradation of the polymer in the device was affected by hydrophilicity of the drug. A reasonable release of estramustine from the device was kept for a period of more than 20 weeks. Furthermore, the release of the drugs in vivo was able to lead to an atrophy of accessory sex organs such as ventral prostates (VP) and right-side seminal vesicle (SV), resulting in pharmacological influence.
Imasaka
K
K
Department of Pharmaceutics, Hoshi University, Tokyo, Japan.
Yoshida
M
M
Fukuzaki
H
H
Asano
M
M
Kumakura
M
M
Mashimo
T
T
Yamanaka
H
H
Nagai
T
T
D000818:Animals; D004343:Drug Implants; D004961:Estramustine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005069:Evaluation Studies as Topic; D005079:Excipients / Q000008:administration & dosage*; D005837:Genitalia, Male / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011091:Polyesters / Q000008:administration & dosage*; D011753:Pyrones / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains
D004343:Drug Implants; D005079:Excipients; D011091:Polyesters; D011753:Pyrones; C073479:poly(epsilon-caprolactone-delta-valerolactone); D004961:Estramustine