Formulation and In Vitro Evaluation of Bisphosphonate Loaded Microspheres for Implantation in Osteolysis

Abstract

Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with alendronate sodium (AS) were prepared for orthopedic as well as dental applications. In orthopedics the aim was to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, while in dentistry it was aimed to treat the alveolar bone resorption caused by periodontitis and also to make the dental treatment using implants easier by reducing the bone loss in patients with osteoporosis. Solvent evaporation method was used to prepare AS loaded PLGA microspheres and emulsion polimerization method was used to prepare AS loaded chitosan microspheres. Particle size, loading efficacy, surface characteristics, and in vitro release characteristics were examined on prepared formulations. After the examination of the scanning electron microscopy photographs of microspheres, chitosan microspheres were observed to have spherical structure and smooth surface characteristics while PLGA microspheres were observed to have spherical porous surface structure. Loading efficacy was found to be 3.30% for chitosan microspheres and 7.70% for PLGA microspheres. It was observed that 85% of AS had been released at the end of the third day from chitosan microspheres whereas 58% was released at the end of the fifth day from PLGA microspheres. It was found that chitosan microspheres gave first order release while PLGA microspheres gave zero order release.

Emulsion cross-linked chitosan/nanohydroxyapatite microspheres for controlled release of alendronate

“…4d), which might be due to the rapid diffusion of AL absorbed on the surface of the microspheres [33,49]. Sibel et al [50] reported that 85 % of AL had been released from the CH/AL microspheres at the end of the third day, which was consistent with this study. Importantly, our studies showed a significantly longer drug release profile displayed in CH/nHA-AL microspheres compared to CH/AL microspheres.…”

Microencapsulation of sodium alendronate reduces drug mucosal damage in rats

“…Some studies were carried out to develop formulations for implantation or injection of the drug for the treatment of bone diseases (Patashnik et al, 1997;Perugini et al, 2001;Weidenauer et al, 2003;2004;Czuryszkiewicz et al, 2005;Samdancioglu et al, 2006;Nafea et al, 2007;Huang et al, 2009;Shi et al, 2009a;. To the best of our knowledge, there is no report in the literature concerning the microencapsulation of sodium alendronate aiming the improvement of its gastrointestinal tolerance following oral administration.…”

Biodegradable polymers for dental tissue engineering and regeneration

“…Hong et al found that the intracellular delivery of estrogen using cationic PLGA microparticles significantly upregulates osteogenic differentiation of human bone marrow mesenchymal stromal cells [157] while PLGA microspheres containing simvastatin [158], endothelial growth factors [159], or dexamethasone [160] significantly enhance bone formation. Other applications of PLGA relate to better osteointegration of titanium implants through PLGA microparticles loaded with growth factors [161,162] and the treatment of alveolar bone resorption with bisphosphonate PLGA microspheres [163]. In particular, injectable PLGA microspheres containing fluvastatin enhanced osteogenesis around titanium implants in the rat tibia [164] and PLGA microparticles loaded with insulin improved biomechanical retention of implants on type I diabetic rats [165].…”