| In vitro-in vivo myotoxicity of intramuscular liposomal formulations. | |
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MedLine Citation:
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PMID: 8893279 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: The first objective was to study the in vitro myotoxicity of empty liposomes and to examine whether liposome size, charge and fluidity affect of liposomal myotoxicity. The second objective was to investigate the effect of liposomal encapsulation on the in vitro and in vivo myotoxicity of loxapine compared to the loxapine commercial preparation (Loxitane). METHODS: The in vitro myotoxicity of empty liposomes and loxapine liposomes was evaluated by the cumulative efflux of the cytosolic enzyme creatine kinase (CK) from the isolated rat extensor digitorum longus (EDL) muscle over a 2 hour period. In the in vivo studies, the area under plasma CK curve over 12 hours was used to evaluate muscle damage. RESULTS: The in vitro myotoxicity for all empty liposomal formulations was not statistically different from negative controls (untreated control muscles and normal saline injected muscles). However, these empty liposomal formulations were significantly less myotoxic than the positive controls (muscles injected with phenytoin and muscle sliced in half). In vitro-in-vivo studies showed that the liposomal encapsulation of loxapine resulted in significant (P < 0.05) reduction in myotoxicity (80% in vitro and 60% in vivo) compared to the commercially available formulation which contains propylene glycol (70% V/V) and polysorbate 80 (5% W/V) prepared at equal concentration. CONCLUSIONS: Results indicate that empty liposomes do not induce myotoxicity. Furthermore, liposomal size, charge and fluidity do not affect myotoxicity. In addition, in vitro and in vivo studies have demonstrated that liposomal encapsulation of loxapine can reduce myotoxicity compared to a formulation containing organic cosolvents. |
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Authors:
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S A al-Suwayeh; I R Tebbett; D Wielbo; G A Brazeau |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pharmaceutical research Volume: 13 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1996 Sep |
Date Detail:
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Created Date: 1997-02-19 Completed Date: 1997-02-19 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1384-8 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutics, University of Florida, College of Pharmacy, J. Hillis Miller Health Center Gainesville 32610, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Creatine Kinase / blood Dopamine Antagonists / toxicity* Drug Carriers / toxicity Injections, Intramuscular Liposomes / toxicity Loxapine / administration & dosage, toxicity* Male Muscle, Skeletal / drug effects*, enzymology Phenytoin / administration & dosage, toxicity Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Dopamine Antagonists; 0/Drug Carriers; 0/Liposomes; 1977-10-2/Loxapine; 57-41-0/Phenytoin; EC 2.7.3.2/Creatine Kinase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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