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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.


In vitro release profiles. Release of a LA and b RAN from AAS-NLCs, AAS-SLNs, the mixture of AAS and unloaded NLCs, and the mixture of AAS and unloaded SLNs (n = 3).
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Fig5: In vitro release profiles. Release of a LA and b RAN from AAS-NLCs, AAS-SLNs, the mixture of AAS and unloaded NLCs, and the mixture of AAS and unloaded SLNs (n = 3).

Mentions: The cumulative release percentage profiles of LA and RAN from the AAS-NLCs, AAS-SLNs, and the mixture of AAS and blank NLCs are shown in Figure 5. The aqueous solubility of LA and RAN in the medium was 849.79 ± 36.95 and 582.06 ± 16.27 µg/mL, respectively, and the sink condition was maintained during the release study. Both SLN and NLC dispersions significantly enhanced the in vitro AAS release for 72 h. The results showed the LA and RAN dispersion from SLNs was 94.6 ± 5.2 and 71.8 ± 1.9%, respectively and from the NLCs was 98.5 ± 4.1 and 79.3 ± 2.7%, respectively. In comparison, their physical mixtures showed LA and RAN from SLNs at 58.8 ± 0.7 and 39.2 ± 1.7%, respectively and from NLCs was 58.8 ± 6.9 and 40.0 ± 2.8%, respectively, under the same experimental conditions. This disparity is most likely due to the disordered crystalline state of the drug that exhibited higher solubilization and was selected for nanoparticle formation [9]. In addition, the total drug released from the NLC formulations was slightly greater than that released from the SLN formulations, which was likely caused by the imperfections in NLCs resulting from the incorporation of liquid lipids into solid lipids [19]. Furthermore, AAS-NLCs exhibited an initial fast release of 12.2 ± 0.7 and 17.2 ± 1.4% for LA and RAN, respectively for 0.5 h, which was possibly due to the portion of AAS that was localized at the surface of the nanoparticles.Figure 5


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)

In vitro release profiles. Release of a LA and b RAN from AAS-NLCs, AAS-SLNs, the mixture of AAS and unloaded NLCs, and the mixture of AAS and unloaded SLNs (n = 3).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: In vitro release profiles. Release of a LA and b RAN from AAS-NLCs, AAS-SLNs, the mixture of AAS and unloaded NLCs, and the mixture of AAS and unloaded SLNs (n = 3).
Mentions: The cumulative release percentage profiles of LA and RAN from the AAS-NLCs, AAS-SLNs, and the mixture of AAS and blank NLCs are shown in Figure 5. The aqueous solubility of LA and RAN in the medium was 849.79 ± 36.95 and 582.06 ± 16.27 µg/mL, respectively, and the sink condition was maintained during the release study. Both SLN and NLC dispersions significantly enhanced the in vitro AAS release for 72 h. The results showed the LA and RAN dispersion from SLNs was 94.6 ± 5.2 and 71.8 ± 1.9%, respectively and from the NLCs was 98.5 ± 4.1 and 79.3 ± 2.7%, respectively. In comparison, their physical mixtures showed LA and RAN from SLNs at 58.8 ± 0.7 and 39.2 ± 1.7%, respectively and from NLCs was 58.8 ± 6.9 and 40.0 ± 2.8%, respectively, under the same experimental conditions. This disparity is most likely due to the disordered crystalline state of the drug that exhibited higher solubilization and was selected for nanoparticle formation [9]. In addition, the total drug released from the NLC formulations was slightly greater than that released from the SLN formulations, which was likely caused by the imperfections in NLCs resulting from the incorporation of liquid lipids into solid lipids [19]. Furthermore, AAS-NLCs exhibited an initial fast release of 12.2 ± 0.7 and 17.2 ± 1.4% for LA and RAN, respectively for 0.5 h, which was possibly due to the portion of AAS that was localized at the surface of the nanoparticles.Figure 5

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.