Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 400, Issue 1-2, Pages 251-259Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2010.08.044
Keywords
Solid lipid nanoparticle; Antisense oligonucleotide; Stability; Cancer therapy; Drug delivery
Categories
Funding
- United State Public Health Service/NIH [P20 RR16456]
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In this study, solid lipid nanoparticles (SLN) loaded with MBO-asGCS oligonucleotide were prepared, characterized and evaluated for cytotoxicity against NCI/ADR-RES human ovary cancer cells. Two types of cetyltrimethyl ammonium bromide (CTAB) stabilized SLN, with or without ceramide VI, were prepared by mixed homogenization/ultrasonication technique. Complexes were characterized for size, zeta-potential, and stability in biorelevant media and against DNaseI activity. Binding and release studies were further confirmed by gel electrophoresis. Cytotoxicity of the SLN against NCI/ADR-RES cells was evaluated by quantizing ATP. SLN with ceramide VI had lower particle size (74.6 nm) with improved stability in RPM! media when compared to reference SLN without ceramide VI (167.16 nm). Both SLN however had similar cytotoxicity profile with an optimum binding at CTAB to MBO-asGCS ratio of 6:1. Blank SLN, and free MBO-asGCS in the presence and absence of free doxorubicin had insignificant effect on the viability of NCI/ADR-RES cells. However, when cells were concurrently treated with MBO-asGCS loaded SLN and free doxorubicin, cell viability significantly decreased to approximately 12%. These results suggested that SLN enhanced internalization and uptake of MBO-asGCS oligonucleotide, which led to the downregulation of GCS and subsequently reversing the resistance of the cells to doxorubicin. (C) 2010 Elsevier B.V. All rights reserved.
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