Improved Biosafety and Transdermal Delivery of Aconitine via Diethylene Glycol Monoethyl Ether-Mediated Microemulsion Assisted with Microneedles

Abstract

In the current study, diethylene glycol monoethyl ether-mediated microemulsions were combined with microneedles for enhanced transdermal aconitine delivery. The oil-in-water microemulsion increasedaconitine solubility and enhanced transdermal drug delivery and assistance with metal microneedles enhanced permeation of the aconitine-loaded microemulsion. Carried by the microemulsion, the in vitro permeability of aconitine was significantly enhanced, and further improved using microneedles. In vivo microdialysis revealed that the subcutaneous local drug concentration reached a high level within 30 min and remained relatively consistent to the end of the experimental period. AUC0-t of the microemulsion group was significantly higher than that of the aqueous solution group, and the microemulsion combined with microneedles group achieved the highest AUC0-t among the tested groups. The microemulsion and microdialysis probe also showed good biocompatibility with skin tissue. The microemulsion could be internalized by HaCaT and CCC-ESF-1 cells via lysosomes. The in vitro cytotoxicity of aconitine toward skin cells was reduced via encapsulation by microemulsion, and the prepared microemulsion developed no skin irritation. Hence, transdermal aconitine delivery and drug biosafety were effectively improved by loading into the microemulsion and assisting with microneedles, and in vivo microdialysis technique is suitable for realtime monitoring of transdermal drug delivery with microemulsion-based drug vehicles.

Emerging era of microneedle array for pharmaceutical and biomedical applications: recent advances and toxicological perspectives

“…safety of MN-based drug, protein, and peptide drug delivery via the original route such as a transdermal route [12]. there are claims for MN toxicity depending on the kind of materials utilized [21], the drug delivery approach [77], and the shape or dimensions of MNs [142]. Besides, the insertion of MNs through the skin can produce inflammation because of the breakdown of cells and produces free radicals that cause skin damage [65,129].…”

“…Because of the microemulsion, the aconitine constant subcutaneous distribution obtained, which resulted in the diminishing the toxicity [142] 4. 5-Fu loaded monomethoxypoly(ethylene glycol)-polycaprolactone NPs integrated HA dissolvable MNs was evaluated for in vitro cytotoxicity by human epidermoid cancer cell line-A431 and the human melanoma cell line-A375 through MTT assay.…”

Ionic Liquid-In-Oil Microemulsions Prepared with Biocompatible Choline Carboxylic Acids for Improving the Transdermal Delivery of a Sparingly Soluble Drug

“…However, the widespread use of this system is restricted to a few drugs only, because of the impermeable nature of the stratum corneum (SC), the outermost layer of the skin [3,4]. To overcome these limitations, many micro-structured fluid systems, including microemulsions, nanoparticles, and permeation enhancers containing other vesicles have been investigated to improve drug delivery efficiency via disrupting and modifying the regular arrangement of the corneocytes of the SC [5,6]. Among these fluid systems, attention has been focused on microemulsions (MEs), usually consisting of water, oil, and surfactant, which are useful colloidal nano-carriers for a TDDS, owing to their thermodynamic stability, high drug-loading capacity, and very low surface tension [7,8].…”

Recent Advances of Microneedles and Their Application in Disease Treatment

“…In addition to meloxicam used for OA, some other drugs have also been combined with MNs technology for the treatment of rheumatoid arthritis, such as methotrexate [ 101 , 102 , 103 ], artemether [ 104 , 105 ], alkaloids [ 106 , 107 ], capsaicin [ 108 ], neurotoxin [ 109 ], triptolide [ 110 ], paeoniflorin [ 111 ], sinomenine [ 112 ] and Etanercept (EN) [ 113 ]. MN transdermal delivery thus offers a promising route of administration for arthritis.…”