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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.


NanoSight image of test formulations. Representative images of a blank control, b C6-labeled NLCs and c C6-labeled SLNs diluted 1,000,000-fold, d a sample treated with C6-labeled NLCs, and e a sample treated with C6-labeled SLNs.
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Fig11: NanoSight image of test formulations. Representative images of a blank control, b C6-labeled NLCs and c C6-labeled SLNs diluted 1,000,000-fold, d a sample treated with C6-labeled NLCs, and e a sample treated with C6-labeled SLNs.

Mentions: No fluorescent nanoparticles were found in the blank control sample (Figure 11a), demonstrating that flaking skin particles did not influence the experimental outcome. The C6-labeled NLCs and SLNs were each diluted 1,000,000-fold and fluorescent nanoparticles were detected (Figure 11b, c). This ensured the sensitivity of the method for small quantities of nanoparticles such as those that might be transported across the skin. As shown in Figure 11d and e, fluorescent nanoparticles were not detected in the receptor fluid after permeation by C6-labeled NLCs or SLNs. It is also believed that rigid particles above 10 nm do not penetrate intact skin [30]. This finding is consistent with reports on lipid nanoparticles, which are not considered to penetrate the SC [14].Figure 11


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)

NanoSight image of test formulations. Representative images of a blank control, b C6-labeled NLCs and c C6-labeled SLNs diluted 1,000,000-fold, d a sample treated with C6-labeled NLCs, and e a sample treated with C6-labeled SLNs.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig11: NanoSight image of test formulations. Representative images of a blank control, b C6-labeled NLCs and c C6-labeled SLNs diluted 1,000,000-fold, d a sample treated with C6-labeled NLCs, and e a sample treated with C6-labeled SLNs.
Mentions: No fluorescent nanoparticles were found in the blank control sample (Figure 11a), demonstrating that flaking skin particles did not influence the experimental outcome. The C6-labeled NLCs and SLNs were each diluted 1,000,000-fold and fluorescent nanoparticles were detected (Figure 11b, c). This ensured the sensitivity of the method for small quantities of nanoparticles such as those that might be transported across the skin. As shown in Figure 11d and e, fluorescent nanoparticles were not detected in the receptor fluid after permeation by C6-labeled NLCs or SLNs. It is also believed that rigid particles above 10 nm do not penetrate intact skin [30]. This finding is consistent with reports on lipid nanoparticles, which are not considered to penetrate the SC [14].Figure 11

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.