Biodegradation and biocompatibility of contraceptive-steroid-loaded poly (DL-lactide-co-glycolide) injectable microspheres: in vitro and in vivo study.
OBJECTIVE
A controlled-release drug delivery of contraceptive steroids levonorgestrel (LNG) and ethinyl estradiol (EE) has been developed by successful encapsulation of LNG and EE in poly (lactide-co-glycolide) (PLG) microspheres.


METHODS
Smooth, spherical, steroid-loaded PLG microspheres with a mean size of 10-25 microm were prepared by using the water/oil/water double-emulsion solvent evaporation method.


RESULTS
In vitro release profiles showed an increased burst release of LNG/EE on Week 1; thereafter, the release was sustained. At the end of Week 7, the release of LNG/EE from 1:5 and 1:10 PLG microspheres was 75.64% and 62.55%. respectively. In vitro degradation studies showed that the PLG microspheres maintained surface integrity up to Week 8 and then eroded completely by Week 20. In an in vivo study, the serum concentration of LNG/EE in rats showed a triphasic release response, with an initial burst release of 8 ng/mL LNG and 14 pg/mL EE on Day 1; thereafter, a controlled release of the drugs to the systemic circulation was maintained until Week 15, maintaining constant drug levels of 2 ng/mL LNG and 3-4 pg/mL EE in the blood. Histological examination of steroid-loaded PLG microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that contraceptive-steroid-loaded microspheres were biocompatible.


CONCLUSIONS
This controlled-release and biocompatible nature of the PLG microspheres may have potential application in contraceptive therapy.
Dhanaraju
Magharla Dasaratha
MD
Department of Pharmaceutics, GIET School of Pharmacy, NH-5, Rajahmundry 533 294, India. mddhanaraju@yahoo.com
Rajkannan
Rajagopalan
R
Selvaraj
Devarajan
D
Jayakumar
Rajadas
R
Vamsadhara
Chandrasekar
C
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D002851:Chromatography, High Pressure Liquid; D003271:Contraceptive Agents, Female / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004355:Drug Stability; D004997:Ethinyl Estradiol / Q000008:administration & dosage; D005260:Female; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D019344:Lactic Acid; D016912:Levonorgestrel / Q000008:administration & dosage; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D051381:Rats; D017208:Rats, Wistar
D001672:Biocompatible Materials; D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004997:Ethinyl Estradiol; D016912:Levonorgestrel