| Formulation and pharmacokinetics of lipid nanoparticles of a chemically sensitive nitrogen mustard derivative: Chlorambucil. | |
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MedLine Citation:
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PMID: 18930127 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipid nanoparticles of the cancer drug Chlorambucil (CLB) were prepared by ultrasonication, using stearic acid as the core lipid. Four types of lipid nanoparticle formulations were studied: (i) stearic acid solid lipid nanoparticles (SLN); (ii) sterically stabilized SLN with pegylated phospholipids as stabilizer; (iii) nanostructured lipid complexes with oleic acid as adjunct lipid; (iv) lipid nanocomplexes with dimethyl dioctadecyl ammonium bromide (DDAB) as surface modifier (LN). Lipid nanoparticles were characterized for particle size, assay and encapsulation efficiency, particle morphology and physico-chemical stability over 90 days. All of the formulations were physically stable, with an average particle size of 147 (+/-10)nm. The drug encapsulation efficiency (DEE) of all the formulations except LN decreased significantly over time (p<0.05), probably due to the expulsion of CLB upon crystallization. This indicated that the presence of DDAB in stearic acid nanoparticles increases DEE, preventing CLB degradation in the aqueous disperse phase. Pharmacokinetic studies of the intravenous LN formulation revealed plasma clearance kinetics were comparable to that of CLB solution (p>0.01), indicating electrostatic charge mediated clearance, as reported earlier. In tissue and tumor distribution studies, lower AUC values of CLB were observed for LN compared to CLB solution in liver, kidneys, heart and lungs. However, higher AUC values of LN formulation as compared to CLB solution (p<0.01) in tumors suggested that the presence of DDAB on the lipid nanoparticles resulted in greater accumulation of the drug in tumors. |
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Authors:
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Puneet Sharma; Srinivas Ganta; William A Denny; Sanjay Garg |
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Publication Detail:
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Type: Journal Article Date: 2008-09-26 |
Journal Detail:
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Title: International journal of pharmaceutics Volume: 367 ISSN: 1873-3476 ISO Abbreviation: Int J Pharm Publication Date: 2009 Feb |
Date Detail:
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Created Date: 2009-01-26 Completed Date: 2009-08-11 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804127 Medline TA: Int J Pharm Country: Netherlands |
Other Details:
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Languages: eng Pagination: 187-94 Citation Subset: IM |
Affiliation:
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School of Pharmacy, The University of Auckland, Private Bag 92019, Auckland, New Zealand. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chlorambucil / administration & dosage, chemistry, pharmacokinetics* Chromatography, High Pressure Liquid Drug Compounding Drug Stability Hydrogen-Ion Concentration Injections, Intravenous Lipids / administration & dosage, chemistry* Male Mice Mice, Inbred C57BL Molecular Structure Nanoparticles / administration & dosage, chemistry* Nitrogen Mustard Compounds / administration & dosage, chemistry, pharmacokinetics Osmolar Concentration Particle Size Solubility Surface Properties Tissue Distribution Ultrafiltration |
| Chemical | |
Reg. No./Substance:
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0/Lipids; 0/Nitrogen Mustard Compounds; 305-03-3/Chlorambucil |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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