Affiliations: Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyama‐Kitamachi 4‐19‐1, Higashi‐Nada, Kobe 658‐8558, Japan | Faculty of Pharmaceutical Sciences, Science University of Tokyo, Shinjuku‐ku Tokyo 162‐0826, Japan
Note: [] Corresponding author: Associate Prof. Makoto Otsuka, Ph.D., Department of Pharmaceutical Technology, Kobe Pharmaceutical University, Motoyama‐Kitamachi 4‐19‐1, Higashi‐Nada, Kobe 658‐8558, Japan. E‐mail: m‐otsuka@kobepharma‐u.ac.jp.
Abstract: Poly (lactide‐co‐glycolide or PLGA) microspheres containing 0.3% (w/w) of estradiol were prepared by a solvent evaporation method. These PLGA microspheres had a wide particle distribution between 0.5 and more than 100 μm. The average size was 76 μm. Physicochemical properties of the microspheres were characterized by X‐ray diffraction patterns, FT‐IR spectra and DSC. In vitro estradiol release was maintained at a constant rate from these PLGA microspheres for 1 month. The loaded drug was totally recovered in the collection buffer within this time period. In vivo experiments were performed on Wistar rats that had received ovariectomy. These rats were fed with a vitamin D‐deficient and Ca‐deficient diet. The combination of ovariectomy and diet induced osteoporosis. PLGA microspheres containing either 50, 100, or 200 μg estradiol were injected into these rats. The plasma estradiol in each rat was monitored for 50 days. These in vivo drug release patterns were found to be different from the one obtained from in vitro release. The Ca‐AUC was not significant different among various dosages administered. However, bone mineral density for rats after the injection of estradiol loaded microspheres was higher than that obtained for the control. This suggested that all estradiol microspheres administration induced bone generation in osteoporosis rats.
Keywords: Poly (lactide‐co‐glycolide) microsphere, drug delivery system, estradiol, osteoporosis rats, in vitro release, plasma calcium level
