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

Guo T, Zhang Y, Zhao J, Zhu C, Feng N - J Nanobiotechnology (2015)

Bottom Line: Microstructure and in vitro/in vivo transdermal delivery characteristics of AAS-loaded NLCs and solid lipid nanoparticles (SLNs) were compared.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People's Republic of China. guoteng1@hotmail.com.

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 AAS 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 AAS. AAS-NLCs showed higher percutaneous permeation than the other preparations. These findings suggest that NLCs could be promising transdermal delivery vehicles for AAS.

No MeSH data available.


Cytotoxicity of alkaloids isolated from AAS solution, AAS-SLNs, AAS-NLCs, unloaded SLNs and unloaded NLCs. a HaCaT cells and b CCC-ESF cells (n = 3).
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Fig6: Cytotoxicity of alkaloids isolated from AAS solution, AAS-SLNs, AAS-NLCs, unloaded SLNs and unloaded NLCs. a HaCaT cells and b CCC-ESF cells (n = 3).

Mentions: Most lipid nanoparticles formed from glycerides or their derivatives are safe and well tolerated by organisms [20]. The in vitro cytotoxicity of AAS, AAS-SLNs, AAS-NLCs, and the empty vehicles (without AAS, defined as blank NLCs and blank SLNs) was evaluated in HaCaT and CCC-ESF cells. As shown in Figure 6, blank NLCs and SLNs showed no serious cytotoxicity at the tested concentrations (cell survival rates were higher than 80%). The viability of HaCaT and CCC-ESF cells treated with various concentrations of the formulations containing AAS was reduced dose-dependently, and both AAS-SLN and AAS-NLC formulations were significantly (p < 0.05) less cytotoxic than the AAS aqueous suspension (1,000 µg/mL) was. These results may be due to the fact that the free drug in the AAS suspension was released and immediately permeated the cells by passive diffusion while the nanoparticles had to be internalized via endocytosis or phagocytosis and released through the drug release process. AAS loaded in the tested nanoparticles achieved a biocompatibility with skin cells that was superior to that of the AAS aqueous suspension.Figure 6


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

Guo T, Zhang Y, Zhao J, Zhu C, Feng N - J Nanobiotechnology (2015)

Cytotoxicity of alkaloids isolated from AAS solution, AAS-SLNs, AAS-NLCs, unloaded SLNs and unloaded NLCs. a HaCaT cells and b CCC-ESF cells (n = 3).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4496826&req=5

Fig6: Cytotoxicity of alkaloids isolated from AAS solution, AAS-SLNs, AAS-NLCs, unloaded SLNs and unloaded NLCs. a HaCaT cells and b CCC-ESF cells (n = 3).
Mentions: Most lipid nanoparticles formed from glycerides or their derivatives are safe and well tolerated by organisms [20]. The in vitro cytotoxicity of AAS, AAS-SLNs, AAS-NLCs, and the empty vehicles (without AAS, defined as blank NLCs and blank SLNs) was evaluated in HaCaT and CCC-ESF cells. As shown in Figure 6, blank NLCs and SLNs showed no serious cytotoxicity at the tested concentrations (cell survival rates were higher than 80%). The viability of HaCaT and CCC-ESF cells treated with various concentrations of the formulations containing AAS was reduced dose-dependently, and both AAS-SLN and AAS-NLC formulations were significantly (p < 0.05) less cytotoxic than the AAS aqueous suspension (1,000 µg/mL) was. These results may be due to the fact that the free drug in the AAS suspension was released and immediately permeated the cells by passive diffusion while the nanoparticles had to be internalized via endocytosis or phagocytosis and released through the drug release process. AAS loaded in the tested nanoparticles achieved a biocompatibility with skin cells that was superior to that of the AAS aqueous suspension.Figure 6

Bottom Line: Microstructure and in vitro/in vivo transdermal delivery characteristics of AAS-loaded NLCs and solid lipid nanoparticles (SLNs) were compared.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People's Republic of China. guoteng1@hotmail.com.

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 AAS 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 AAS. AAS-NLCs showed higher percutaneous permeation than the other preparations. These findings suggest that NLCs could be promising transdermal delivery vehicles for AAS.

No MeSH data available.