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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.


DSC curves. Representative DSC curves of A bulk drug, B Precirol ATO5, C cryoprotectant, D physical mixture, E AAS-NLCs, and F AAS-SLNs.
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Fig3: DSC curves. Representative DSC curves of A bulk drug, B Precirol ATO5, C cryoprotectant, D physical mixture, E AAS-NLCs, and F AAS-SLNs.

Mentions: Differential scanning calorimetry (DSC) was performed to investigate the melting and crystallization behavior of the lipid molecules and drugs in the nanoparticle preparations [17]. As shown in Figure 3, the bulk drug had endothermic peaks at 208.6 and 269.0°C, the Precirol ATO 5 displayed a melting point of 61.1°C, and the cryoprotectant (mannitol) exhibited an endothermic peak at 159.3°C. The physical mixture heating curves exhibited three endothermic peaks that corresponded to the melting points of the three components. These included the reduced endothermic peak of the bulk drug at 269.0°C and the moving endothermic peak of Precirol ATO 5 at 51.5°C. The results indicated that the enhanced dissolution of the partial bulk drug in the solid lipids as the temperature rose led to changes in crystalline structure. All the endothermic peaks of AAS disappeared and the peak of Precirol ATO 5 was significantly shifted to the right in the AAS-NLC and AAS-SLN heating curves, indicating an increase in lattice defects in the AAS-NLC and AAS-SLN preparations. The results suggest that the drug was homogeneously dispersed in the nanoparticles in a disordered crystalline state.Figure 3


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)

DSC curves. Representative DSC curves of A bulk drug, B Precirol ATO5, C cryoprotectant, D physical mixture, E AAS-NLCs, and F AAS-SLNs.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: DSC curves. Representative DSC curves of A bulk drug, B Precirol ATO5, C cryoprotectant, D physical mixture, E AAS-NLCs, and F AAS-SLNs.
Mentions: Differential scanning calorimetry (DSC) was performed to investigate the melting and crystallization behavior of the lipid molecules and drugs in the nanoparticle preparations [17]. As shown in Figure 3, the bulk drug had endothermic peaks at 208.6 and 269.0°C, the Precirol ATO 5 displayed a melting point of 61.1°C, and the cryoprotectant (mannitol) exhibited an endothermic peak at 159.3°C. The physical mixture heating curves exhibited three endothermic peaks that corresponded to the melting points of the three components. These included the reduced endothermic peak of the bulk drug at 269.0°C and the moving endothermic peak of Precirol ATO 5 at 51.5°C. The results indicated that the enhanced dissolution of the partial bulk drug in the solid lipids as the temperature rose led to changes in crystalline structure. All the endothermic peaks of AAS disappeared and the peak of Precirol ATO 5 was significantly shifted to the right in the AAS-NLC and AAS-SLN heating curves, indicating an increase in lattice defects in the AAS-NLC and AAS-SLN preparations. The results suggest that the drug was homogeneously dispersed in the nanoparticles in a disordered crystalline state.Figure 3

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.