Enhanced transdermal permeability and drug deposition of rheumatoid arthritis via sinomenine hydrochloride-loaded antioxidant surface transethosome

Abstract

Hui Song,1,2 Jin Wen,3 He Li,1,2 Ya Meng,1,2 Yujia Zhang,1,2 Nan Zhang,1,2 Wensheng Zheng1,21State Key Laboratory of Bioactive Substance and Function of Natural Medicines; 2Beijing City Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, People’s Republic of China; 3Academic Department, Chinese Pharmaceutical Association, Beijing, 100022, People’s Republic of ChinaBackground: Transdermal drug delivery system (TDDS) curing rheumatoid arthritis (RA) for long-term treatment can improve patients’ compliance and reduce the accumulation of drug side effects. However, TDDS is constrained by the tight junction of the stratum corneum and low permeation efficiency. It is necessary to adopt proper permeation methods to ensure the therapeutic effect. The transethosome (TE), which is derived from transfersome and ethosome (E), containing a high content of ethanol along with an edge activator or permeation enhancer, has superior deformability and higher permeation efficiency.Methods and Results: In this study, sinomenine hydrochloride-loaded TE was decorated with ascorbic acid to form antioxidant surface transethosome (AS-TE). It was revealed that TE and AS-TE containing sodium deoxycholate can effectively increase the entrapment efficiency of hydrophilic drug, and has superior deformability and higher permeation efficiency than E group. The plasma pharmacokinetics of rabbits showed that TE group and AS-TE group had similar blood concentration and bioavailability; however, micro-dialysis on synovial fluid demonstrated that AS-TE group had higher drug concentration. In RA rat models, the alleviation of the joint swell of AS-TE group was more obvious in the course of 3 weeks of treatment. The inflammatory cytokines and erythrocyte sedimentation rate were significantly lower than those in the negative control group and TE1 group.Conclusion: AS-TE, which can enhance transdermal permeability and drug deposition for the oxidant stress of RA, had further research potential to serve as a TDDS of RA.Keywords: transdermal drug delivery system, antioxidant surface, transethosome, oxidant stress, micro-dialysis

Keywords

• transdermal drug delivery system
• antioxidant surface
• transethosome
• oxidant stress
• micro-dialysis