ABSTRACT
Background: Inflammatory bone resorption in periodontitis can lead to tooth loss. Systemic administration of bisphosphonates such as risedronate for preventing bone resorption can cause adverse effects. Alginate hydrogel (ALG) and poly (lactic acid-co-glycolic acid) (PLGA) microparticles have been studied as drug delivery systems for sustained release of drugs. Therefore, the release pattern of risedronate from PLGA microparticles embedded with ALG was studied as a drug delivery system for sustained release of the drug, which can be used in local administrations. Methods: Risedronate-containing PLGA microparticles were fabricated using double emulsion solvent evaporation technique. Ionic cross-linking method was used to fabricate risedronate-loaded ALG. Risedronate-containing PLGA microparticles were then coated with ALG. The calibration curve of risedronate was traced to measure encapsulation efficiency (EE) and study the release pattern. Scanning electron microscope (SEM) imaging was carried out, and cell toxicity was examined using MTT assay. Statistical analysis of data was carried out using SPSS ver. 20 software, via one-way ANOVA and Tukey's tests. Results: SEM imaging showed open porosities on ALGs. The mean EE of PLGA microparticles for risedronate was 57.14 ± 3.70%. Risedronate released completely after 72 h from ALG, and the cumulative release was significantly higher (p = 0.000) compared to PLGA microspheres coated with ALG, which demonstrated sustained released of risedronate until day 28. Risedronate-loaded ALG showed a significant decrease in gingival fibroblasts cell viability (p < 0.05). Conclusion: Alginate-coated PLGA microspheres could release risedronate in a sustained and controlled way and also did not show cell toxicity. Therefore, they seem to be an appropriate system for risedronate delivery in local applications.
Subject(s)
Alginates/chemistry , Bone Diseases/drug therapy , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Risedronic Acid/metabolism , Cell Line , Delayed-Action Preparations/metabolism , Hydrogels/chemistry , MicrospheresABSTRACT
CONTEXT: Osteoporosis (OP) is the most common metabolic bone disease predominantly found in elderly people. It is associated with reduced bone mineral density, results in a higher probability of fractures, especially of the hip, vertebrae, and distal radius. Worldwide prevalence of OP is considered a serious public health concern. OBJECTIVE: The purpose of the present work was to develop and evaluate polymeric nanoparticles (NPs) of risedronate sodium (RIS) for the treatment of OP using intranasal (IN) route in order to reduce peripheral toxic effects. MATERIALS AND METHODS: Polymeric NPs of RIS were prepared by nanoprecipitation methods. Formulations were developed and evaluated in context to in vitro drug release, ex vivo permeation, in vivo study, and biochemical studies. RESULTS AND DISCUSSIONS: The particles size, entrapment efficiency (EE) (%), and loading capacity (LC) (%) of optimized formulations were found to be 127.84 ± 6.33 nm, 52.65 ± 5.21, and 10.57 ± 1.48, respectively. Release kinetics showed diffusion-controlled, Fickian release pattern. Ex vivo permeation study showed RIS from PLGA-NPs permeated significantly (p < 0.05) through nasal mucosa. In vivo study showed a marked difference in micro-structure (trabeculae) in bone internal environment. Biochemical estimation of treated group and RIS PLGA indicated a significant recovery (p < 0.01) as compared with the toxic group. CONCLUSION: Polymeric NPs of RIS were prepared successfully using biodegradable polymer (PLGA). Intranasal delivery showed a good result in in vivo study. Thus PLGA-NPs have great potential for delivering the RIS for the treatment and prevention of OP after clinical evaluation in near future.
