Nanoemulsions for dermal controlled release of oleanolic and ursolic acids: In vitro, ex vivo and in vivo characterization

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2015-06, Vol.130, p.40-47
• Main Authors: Alvarado, H.L., Abrego, G., Souto, E.B., Garduño-Ramirez, M.L., Clares, B., García, M.L., Calpena, A.C.
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Anti-inflammatory activity; Biocompatibility; Biomedical materials; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Droplets; Drug Delivery Systems - methods; Drug Stability; Drugs; Emulsions; Humans; Kinetics; Mathematical models; Microscopy, Electron, Transmission; Nanoemulsion; Nanoemulsions; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nanostructure; Oleanolic acid; Oleanolic Acid - administration & dosage; Oleanolic Acid - chemistry; Oleanolic Acid - pharmacokinetics; Penetration; Permeation; Skin - metabolism; Skin Absorption; Solubility; Temperature; Topical administration; Triterpenes - administration & dosage; Triterpenes - chemistry; Triterpenes - pharmacokinetics; Ursolic Acid; Viscosity
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.03.062

•Natural or synthetic mixtures of pentacyclic triterpenes were formulated in nanoemulsions (NEs).•NEs followed Korsmeyer-Peppas kinetic model for triterpenes (oleanolic/ursolic acids) release.•Natural mixtures showed a greater anti-inflammatory effect than synthetic mixtures.•NEs demonstrated low viscosity and kept the small droplet size. The aim of the present study was to design and optimize a nanoemulsion for dermal administration of mixtures of natural or synthetic pentacyclic triterpenes with recognized anti-inflammatory activity. The composition of the developed nanoemulsions was obtained from pseudo-ternary phase diagrams, composed of castor oil as the oil phase, labrasol as the surfactant, transcutol-P as co-surfactant and propylene glycol as the aqueous phase. Different ratios of surfactant/co-surfactant mixture (Smix) (4:1, 3:1, 2:1, 1:1, 1:2 and 1:4) were produced, and Smix 4:1 was chosen based on the greater area of optimal nanoemulsion conditions. Two different nanoemulsions of mean droplet size below 600nm were produced, loading mixtures of natural or synthetic pentacyclic triterpenes, respectively. The viscosity of nanoemulsion containing natural pentacyclic triterpenes was 51.97±4.57mPas and that loaded with synthetic mixtures was 55.33±0.28mPas. The studies of release and skin permeation were performed using Franz diffusion cells, adjusting the release kinetics of both formulations to Korsmeyer-Peppas model. No significant differences in permeation parameters between the two nanoemulsions were observed. The amount of drug retained in the skin was higher than the amount of drug that has permeated, favoring a local action. The results of the in vivo tests demonstrated that the developed formulations were not toxic and not irritant to the skin. The formulation loading a mixture of natural triterpenes showed greater ability to inhibit inflammation than that loading the synthetic mixture. The findings clearly corroborate the added value of o/w nanoemulsions for dermal delivery of pentacyclic triterpenes.