Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems

Citation
H. Kranz et al., Myotoxicity studies of injectable biodegradable in-situ forming drug delivery systems, INT J PHARM, 212(1), 2001, pp. 11-18
Citations number
26
Categorie Soggetti
Pharmacology & Toxicology
Journal title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
ISSN journal
03785173 → ACNP
Volume
212
Issue
1
Year of publication
2001
Pages
11 - 18
Database
ISI
SICI code
0378-5173(20010105)212:1<11:MSOIBI>2.0.ZU;2-M
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 usin g the isolated rodent skeletal muscle model by measuring the cumulative cre atine kinase (CK) efflux. For the in-vivo study, following intramuscular in jection (i.m.) into male Sprague Dawley rats, the area under the plasma CK- curve was used to evaluate muscle damage. The formulations included ISM-sys tems la poly (lactide)-solvent phase dispersed into an external oil phase a nd poly (lactide) solutions (in-situ implant systems). Phenytoin and normal saline served as positive and negative controls, respectively. Poly (lacti de) in different solvents (in-situ implant systems) resulted in 14.4-24.3 t imes higher CK-values compared to normal saline, indicating a high myotoxic potential. With the ISM-system, the CK-release was significantly lower, de creased with a lower polymer phase: oil phase ratio, and approached the val ues of normal saline at a ratio of 1:4. Bupivacaine HCl- and Buserelin acet ate- containing ISM-systems resulted in significantly lower CK-levels when compared to the corresponding drug formulation in normal saline. The in-viv o studies confirmed the in-vitro data and showed good muscle compatibility of the ISM-systems. (C) 2001 Elsevier Science B.V. All rights reserved.