Functionalized multiwalled carbon nanotube-ethosomes for transdermal delivery of ketoprofen: Ex vivo and in vivo evaluation

Transdermal administration is a promising non-invasive and convenient method of drug delivery in clinic and avoid serious gastrointestinal adverse reactions. In this study, a hybrid nanocarrier was developed to facilitate transdermal delivery of drugs. The low water-soluble ketoprofen (KP) was ultrasonically loaded on functionalized multi-walled carbon nanotubes (f-MWCNTs), and the preparation process was optimized using Box-Behnken design. Then, KP-loaded f-MWCNTs composite ethosomes (f-MWCNTs-KP-ES) were prepared by a single-step injection technology. Over the study period, the preparation was verified by a series of characterizations, and ex vivo release characteristics, ex vivo permeation of rat skin and in vivo pharmacokinetics were studied. The characterization results consistently showed that f-MWCNTs-KP-ES were successfully prepared. The preparation can obviously improve the solubility of KP. Ex vivo permeation experiments showed that had a sustained release effect and the skin penetration rate of f-MWCNTs-KP-ES gel is the fastest, with a cumulative permeation amount of 602.35 +/- 41.06 mu g/cm(2). In addition, both ethosomes and f-MWCNTs could increase the retention of drugs and form drug reservoirs. Fluorescence microscope images of rat skin clearly illustrated the faster and deeper penetration of f-MWCNTs composite ethosomes formulation loaded with rhodamine B (RB) (f-MWCNT-RB-ES). In vivo pharmacokinetic experiments showed the area under the drug time curve (AUC(0-t)) and elimination halflife (T-1/2 beta) of f-MWCNTs-KP-ES gel group were significantly increased and prolonged compared with KP commercial gel group, respectively. The overall data indicate that the f-MWCNTs composite ethosomes formulation is a promising transdermal drug delivery system.