In this study, transdermal
etodolac-loaded cubosomes were developed in order to relieve patient
pain and joints stiffness by providing stable
etodolac concentration at the targeting sites through controlled
drug delivery via the noninvasive skin route with more sustaining and less frequent dosing. Different ratios and percentages of
poloxamer 407 and
monoolein were used to formulate the cubosomes using emulsification and homogenization processes. The
etodolac-loaded cubosomes showed particle size values ranging from 135.95 to 288.35 nm and zeta potential values ranging from -18.40 to -36.10 mV. All the cubosomes offered an encapsulation efficiency value of about 100% and showed
drug loading capacity ranging from 1.28 to 6.09%. The in vitro drug release studies revealed a controlled drug release profile with a drug release rate up to 15.08%/h. Increasing
poloxamer concentration in
etodolac-loaded cubosomes resulted in nanoparticles with less particle size and faster drug release. The particles exhibited cubic and hexagonal shapes. The DSC and X-ray analysis demonstrated that the
drug was encapsulated in the cubosomes bicontinuous structures in amorphous form. In addition, investigated cubosomes exhibited fast
drug penetration through excited mice skin followed by slower
drug penetration for up to 24 h. The pharmacokinetic study in human volunteers showed that the selected
etodolac-loaded cubosomes enhanced the bioavailability of
etodolac as compared to the oral capsules (266.11%) with evidence of longer half-life and higher MRT that reached 18.86 and 29.55 h, respectively. The
etodolac-loaded cubosomes propose a promising system for treatment of
arthritis simply through skin application.