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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.


Effect of optimization of the process parameters of high-pressure homogenization method. On a particle size and b polydispersity index.
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Fig1: Effect of optimization of the process parameters of high-pressure homogenization method. On a particle size and b polydispersity index.

Mentions: The stirring rate (rpm), stirring time (min), homogenization pressure (bar), homogenization cycle, and cooling temperature were evaluated to optimize the preparation of the AAS-NLCs. As shown in Figure 1, the particle size and polydispersity index (PDI) were reduced as the stirring rate was slowed or the stirring time was lengthened. As the homogenization pressure increased, the particle size and PDI were reduced but subsequently increased if the pressure continued to increase. Moreover, particle size decreased as the number of homogenization cycles decreased. In addition, a small particle size and low PDI were produced by cooling the formulation to room temperature in an ice bath. It was previously reported that the instability of the preparation system is caused by an increase in the kinetic energy of droplets due to the increase in homogenization pressure and number of homogenization cycles [15]. Therefore, the production parameters were set as follows: stirring rate, 5,000 rpm; stirring time, 10 min; homogenization pressure, 800 bar; cooling temperature, 0°C; and five homogenization cycles were performed.Figure 1


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)

Effect of optimization of the process parameters of high-pressure homogenization method. On a particle size and b polydispersity index.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Effect of optimization of the process parameters of high-pressure homogenization method. On a particle size and b polydispersity index.
Mentions: The stirring rate (rpm), stirring time (min), homogenization pressure (bar), homogenization cycle, and cooling temperature were evaluated to optimize the preparation of the AAS-NLCs. As shown in Figure 1, the particle size and polydispersity index (PDI) were reduced as the stirring rate was slowed or the stirring time was lengthened. As the homogenization pressure increased, the particle size and PDI were reduced but subsequently increased if the pressure continued to increase. Moreover, particle size decreased as the number of homogenization cycles decreased. In addition, a small particle size and low PDI were produced by cooling the formulation to room temperature in an ice bath. It was previously reported that the instability of the preparation system is caused by an increase in the kinetic energy of droplets due to the increase in homogenization pressure and number of homogenization cycles [15]. Therefore, the production parameters were set as follows: stirring rate, 5,000 rpm; stirring time, 10 min; homogenization pressure, 800 bar; cooling temperature, 0°C; and five homogenization cycles were performed.Figure 1

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.