title: A study of the antiresorptive activity of salmon calcitonin microspheres using cultured osteoclastic cells.
abstract: The purpose of this study was to evaluate salmon calcitonin (sCT) microspheres in vitro for their antiresorptive activity using cultured osteoclastic cells. The antiresorptive activity of sCT-loaded microspheres, prepared from a low molecular weight hydrophilic poly (lactide-co-glycolide) polymer (PLGA), was studied using bone marrow culture cells harvested from juvenile rats and cultured on slices of devitalized bone for up to 4 weeks. The resorptive activity of osteoclastic cells was quantified in terms of number and type of resorption pits and total area of resorption. Microspheres containing 5.1% sCT released 70% peptide in 2 weeks and 88% in 4 weeks. All sCT treatments inhibited total resorptive activity. A dose-dependent decrease in resorption was observed with sCT microspheres at 2 weeks. The high dose (10 mg of microspheres) produced a 99.5% decrease in resorption at 3 weeks, while the low dose (1 mg) produced an 80% reduction. Exposure of cultures to soluble sCT and sCT-loaded microspheres caused a decrease in the number of large pits, which were the predominant type formed in control cultures. Thus, this system could serve as an in vitro method to evaluate the antiresorptive effect of PLGA-sCT microspheres.
authors.affiliation: Inhale Therapeutic Systems, San Carlos, CA 94070, USA.
authors.forename: Bhas A
authors.initials: BA
authors.lastname: Dani
authors.forename: Adrian T
authors.initials: AT
authors.lastname: Raiche
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002116:Calcitonin / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D019344:Lactic Acid / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008863:Microspheres; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C028815:salmon calcitonin; D002116:Calcitonin