Nanostructured lipid carriers for percutaneous administration of alkaloids isolated from Aconitum sinomontanum

Journal Reference

J Nanobiotechnology. 2015 Jul 10;13:47.

Guo T¹, Zhang Y², Zhao J³, Zhu C⁴, Feng N⁵.

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Abstract

BACKGROUND:

Lipid-based nanosystems have great potential for transdermal drug delivery. In this study, nanostructured lipid carriers (NLCs) for short-acting alkaloids lappacontine (LA) and ranaconitine (RAN) isolated from Aconitum sinomontanum (AAS) at 69.47 and 9.16% (w/w) yields, respectively, were prepared to enhance percutaneous permeation. Optimized NLC formulations were evaluated using uniform design experiments. Microstructure and in vitro/in vivo transdermal delivery characteristics of AAS-loaded NLCs and solid lipid nanoparticles (SLNs) were compared. Cellular uptake of fluorescence-labeled nanoparticles was probed using laser scanning confocal microscopy and fluorescence-activated cell sorting. Nanoparticle integrity during transdermal delivery and effects on the skin surface were also investigated.

RESULTS:

NLC formulations were less cytotoxic than the Aconitum sinomontanum solution in HaCaT and CCC-ESF cells. Moreover, coumarin-6-labeled NLCs showed biocompatibility with HaCaT and CCC-ESF cells, and their cellular uptake was strongly affected by cholesterol and lipid rafts. Significantly greater cumulative amounts of NLC-associated LA and RAN than SLN-associated alkaloids penetrated the rat skin in vitro. In vivo microdialysis showed higher area under the concentration-time curve (AUC)0-t for AAS-NLC-associated LA and RAN than for AAS-SLN-associated alkaloids.

CONCLUSIONS:

NLC formulations could be good transdermal systems for increasing biocompatibility and decreasing cytotoxicity of Aconitum sinomontanum. AAS-NLCs showed higher percutaneous permeation than the other preparations. These findings suggest that NLCs could be promising transdermal delivery vehicles for Aconitum sinomontanum.

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