Mixed backbone antisense glucosylceramide synthase oligonucleotide (MBO-asGCS) loaded solid lipid nanoparticles: in vitro characterization and reversal of multidrug resistance in NCI/ADR-RES cells.

Abstract:

: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 RPMI 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.

journal_name

Int J Pharm

authors

Siddiqui A,Patwardhan GA,Liu YY,Nazzal S

doi

10.1016/j.ijpharm.2010.08.044

subject

Has Abstract

pub_date

2010-11-15 00:00:00

pages

251-9

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(10)00674-5

journal_volume

400

pub_type

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