Solid Lipid Nanoparticles Formulated for Transdermal Aconitine Administration and Evaluated In Vitro and In Vivo.
In this study, solid lipid nanoparticles were formulated for transdermal delivery of aconitine to improve its safety and permeability. Aconitine-loaded solid lipid nanoparticles were formulated as an oil-in-water microemulsion. Drug encapsulation efficiencies for these formulations were higher than 85%, and correlated positively with levels of surfactant and oil matrix. The size of the solid lipid nanoparticles was increased with an increase of the oil matrix, and reduction of the surfactant levels. Compared with an ethanol tincture, all the tested solid lipid nanoparticle formulations achieved improved transdermal fluxes and drug deposition in skin in vitro. Real-time monitoring of drug distribution in rat dermis using in vivo microdialysis showed that aconitine concentration was markedly higher following application of solid lipid nanoparticles, compared to tincture, throughout the experimental period. A regional comparison of rat skin found that application of solid lipid nanoparticles to the scapular region resulted in higher AUC(0-t) and C(max), compared to those achieved with application to the abdomen or chest (p < 0.05). In contrast, the application to the chest resulted in the lowest AUC(0-t) and C(max). Together with findings of a structural study of the skin, these results indicated that the drug accumulated more readily in thicker skin regions, and to a lesser extent in well-perfused skin, because of drug transfer to capillaries. The superior transdermal permeability of aconitine-loaded solid lipid nanoparticles contributed to stronger anti-inflammatory and analgesic effects on mouse in vivo models of pain than the tincture (p < 0.05). In vitro and in vivo studies indicated that smaller particle sizes of solid lipid nanoparticles enhanced the transdermal permeability of aconitine, which can promote drug efficacy, reduce administration time, and improve medication safety.
Yong-Tai
YT
Zhang
Meng-Qing
MQ
Han
Li-Na
LN
Shen
Ji-Hui
JH
Zhao
Nian-Ping
NP
Feng
D000157:Aconitine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000700:Analgesics / Q000008:administration & dosage; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D008055:Lipids / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008055:Lipids; D000157:Aconitine