Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems.
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| Abstract |
The objective of the study was to investigate the potential in-vitro and in-vivo myotoxicity of different in-situ forming biodegradable drug delivery systems, namely in-situ Microparticle (ISM) systems and polymer solutions (in-situ implant systems). The acute myotoxicity was evaluated in-vitro using the isolated rodent skeletal muscle model by measuring the cumulative creatine kinase (CK) efflux. For the in-vivo study, following intramuscular injection (i.m.) into male Sprague Dawley rats, the area under the plasma CK-curve was used to evaluate muscle damage. The formulations included ISM-systems [a poly (lactide)-solvent phase dispersed into an external oil phase] and poly (lactide) solutions (in-situ implant systems). Phenytoin and normal saline served as positive and negative controls, respectively. Poly (lactide) in different solvents (in-situ implant systems) resulted in 14.4-24.3 times higher CK-values compared to normal saline, indicating a high myotoxic potential. With the ISM-system, the CK-release was significantly lower, decreased with a lower polymer phase: oil phase ratio, and approached the values of normal saline at a ratio of 1:4. Bupivacaine HCl- and Buserelin acetate- containing ISM-systems resulted in significantly lower CK-levels when compared to the corresponding drug formulation in normal saline. The in-vivo studies confirmed the in-vitro data and showed good muscle compatibility of the ISM-systems.
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| Authors | H Kranz, G A Brazeau, J Napaporn, R L Martin, W Millard, R Bodmeier |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 212 Issue 1 Pg. 11-8 (Jan 05 2001) ISSN: 0378-5173 [Print] Netherlands |
| PMID | 11165816 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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