title: Evaluation of PLGA microsphere size effect on myotoxicity using the isolated rodent skeletal muscle model.
abstract: The present work investigated the magnitude of microsphere-induced acute myotoxicity and determined whether this myotoxicity is related to microsphere size and/or reconstitution solvent. Using a high molecular weight poly(dl-lactide-co-glycolide) copolymer, the myotoxicity of two different size microsphere formulations (3.6 microns and 19 microns) in normal saline or distilled water was quantified using a previously validated isolated rat muscle system. Overall, microspheres were found to be relatively nontoxic compared to known myotoxic agents (e.g., phenytoin) and control muscles. The smaller microspheres were found to be significantly more myotoxic than larger microspheres. Furthermore, the myotoxicity was lower in large microspheres reconstituted with normal saline or normal saline with 0.5% (w/v) carboxymethylcellulose (to prevent aggregation) compared to those reconstituted with distilled water. Smaller microspheres were found to be extremely difficult to inject, due to aggregation, which could not be prevented by the addition of carboxymethylcellulose. This study suggests that larger microspheres are less myotoxic than smaller microspheres.
authors.affiliation: Department of Pharmaceutics, University of Florida, College of Pharmacy, J. Hillis Miller Health Center, Gainesville 32610, USA.
authors.forename: G A
authors.initials: GA
authors.lastname: Brazeau
authors.forename: M
authors.initials: M
authors.lastname: Sciame
authors.forename: S A
authors.initials: SA
authors.lastname: al-Suwayeh
authors.forename: E
authors.initials: E
authors.lastname: Fattal
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000633:toxicity*; D003402:Creatine Kinase / Q000378:metabolism; D019344:Lactic Acid / Q000633:toxicity*; D008297:Male; D008863:Microspheres; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology*; D009135:Muscular Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003402:Creatine Kinase