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.

journal_name

Pharm Dev Technol

authors

Brazeau GA,Sciame M,al-Suwayeh SA,Fattal E

doi

10.3109/10837459609022596

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

279-83

issue

3

eissn

1083-7450

issn

1097-9867

journal_volume

1

pub_type

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