Nanostructured Lipid Carriers for Percutaneous Administration of Alkaloids Isolated from Aconitum Sinomontanum

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2015 Jul 10

PMID 26156035

Citations 13

Authors

Teng Guo

Yongtai Zhang

Jihui Zhao

Chunyun Zhu

Nianping Feng

Affiliations

Soon will be listed here.

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.

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References

BISSET N . Arrow poisons in China. Part II. Aconitum--botany, chemistry, and pharmacology. J Ethnopharmacol. 1981; 4(3):247-336. DOI: 10.1016/0378-8741(81)90001-5. View

Xie F, Wang H, SHU H, Li J, Jiang J, Chang J . Separation and characterization of the metabolic products of lappaconitine in rat urine by high-performance liquid chromatography. J Chromatogr. 1990; 526(1):109-18. DOI: 10.1016/s0378-4347(00)82488-3. View

Sit K, Bay B, Wong K . Effect of genistein, a tyrosine-specific protein kinase inhibitor, on cell rounding by pH upshifting. In Vitro Cell Dev Biol Anim. 1993; 29A(5):395-402. DOI: 10.1007/BF02633988. View

Wang L, Rothberg K, Anderson R . Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation. J Cell Biol. 1993; 123(5):1107-17. PMC: 2119875. DOI: 10.1083/jcb.123.5.1107. View

Kuntsche J, Westesen K, Drechsler M, Koch M, Bunjes H . Supercooled smectic nanoparticles: a potential novel carrier system for poorly water soluble drugs. Pharm Res. 2004; 21(10):1834-43. DOI: 10.1023/b:pham.0000045237.46019.6e. View

Manjunath K, Venkateswarlu V . Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration. J Control Release. 2005; 107(2):215-28. DOI: 10.1016/j.jconrel.2005.06.006. View

Boucrot E, Saffarian S, Massol R, Kirchhausen T, Ehrlich M . Role of lipids and actin in the formation of clathrin-coated pits. Exp Cell Res. 2006; 312(20):4036-48. PMC: 2785547. DOI: 10.1016/j.yexcr.2006.09.025. View

Bondi M, Craparo E, Giammona G, Cervello M, Azzolina A, Diana P . Nanostructured lipid carriers-containing anticancer compounds: preparation, characterization, and cytotoxicity studies. Drug Deliv. 2007; 14(2):61-7. DOI: 10.1080/10717540600739914. View

Schafer-Korting M, Mehnert W, Korting H . Lipid nanoparticles for improved topical application of drugs for skin diseases. Adv Drug Deliv Rev. 2007; 59(6):427-43. DOI: 10.1016/j.addr.2007.04.006. View

10.

Bunjes H, Unruh T . Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv Drug Deliv Rev. 2007; 59(6):379-402. DOI: 10.1016/j.addr.2007.04.013. View

11.

Fang J, Fang C, Liu C, Su Y . Lipid nanoparticles as vehicles for topical psoralen delivery: solid lipid nanoparticles (SLN) versus nanostructured lipid carriers (NLC). Eur J Pharm Biopharm. 2008; 70(2):633-40. DOI: 10.1016/j.ejpb.2008.05.008. View

12.

Hosoi R, Matsuyama Y, Hirose S, Koyama Y, Matsuda T, Gee A . Characterization of (14)C-acetate uptake in cultured rat astrocytes. Brain Res. 2008; 1253:69-73. DOI: 10.1016/j.brainres.2008.11.068. View

13.

Elnaggar Y, El-Massik M, Abdallah O . Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm. 2009; 380(1-2):133-41. DOI: 10.1016/j.ijpharm.2009.07.015. View

14.

Cevc G, Vierl U . Nanotechnology and the transdermal route: A state of the art review and critical appraisal. J Control Release. 2009; 141(3):277-99. DOI: 10.1016/j.jconrel.2009.10.016. View

15.

Zhuang C, Li N, Wang M, Zhang X, Pan W, Peng J . Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm. 2010; 394(1-2):179-85. DOI: 10.1016/j.ijpharm.2010.05.005. View

16.

Chiu Y, Ho Y, Chen Y, Peng S, Ke C, Chen K . The characteristics, cellular uptake and intracellular trafficking of nanoparticles made of hydrophobically-modified chitosan. J Control Release. 2010; 146(1):152-9. DOI: 10.1016/j.jconrel.2010.05.023. View

17.

Liu Y, Wang P, Sun C, Feng N, Zhou W, Yang Y . Wheat germ agglutinin-grafted lipid nanoparticles: preparation and in vitro evaluation of the association with Caco-2 monolayers. Int J Pharm. 2010; 397(1-2):155-63. DOI: 10.1016/j.ijpharm.2010.06.030. View

18.

Manconi M, Sinico C, Caddeo C, Vila A, Valenti D, Fadda A . Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin. Int J Pharm. 2011; 412(1-2):37-46. DOI: 10.1016/j.ijpharm.2011.03.068. View

19.

Seong K, Seo H, Ahn W, Yoo D, Cho S, Khang G . Enhanced cytosolic drug delivery using fully biodegradable poly(amino oxalate) particles. J Control Release. 2011; 152(2):257-63. DOI: 10.1016/j.jconrel.2011.02.025. View

20.

Tiwari R, Pathak K . Nanostructured lipid carrier versus solid lipid nanoparticles of simvastatin: comparative analysis of characteristics, pharmacokinetics and tissue uptake. Int J Pharm. 2011; 415(1-2):232-43. DOI: 10.1016/j.ijpharm.2011.05.044. View