Curcumin nanoemulsion for transdermal application: formulation and evaluation.

The aim of this work is to develop a curcumin nanoemulsion for transdermal delivery. The incorporation of curcumin inside a nanoglobul should improve curcumin stability and permeability. A nanoemulsion was prepared by the self-nanoemulsification method, using an oil phase of glyceryl monooleate, Cremophor RH40 and polyethylene glycol 400. Evaluation of the nanoemulsion included analysis of particle size, polydispersity index, zeta potential, physical stability, Raman spectrum and morphology. In addition, the physical performance of the nanoemulsion in Viscolam AT 100P gel was studied. A modified vertical diffusion cell and shed snake skin of Python reticulatus were used to study the in vitro permeation of curcumin. A spontaneously formed stable nanoemulsion has a loading capacity of 350 mg curcumin/10 g of oil phase. The mean droplet diameter, polydispersity index and zeta potential of optimized nanoemulsion were 85.0 ± 1.5 nm, 0.18 ± 0.0 and -5.9 ± 0.3 mV, respectively. Curcumin in a nanoemulsion was more stable than unencapsulated curcumin. Furthermore, nanoemulsification significantly improved the permeation flux of curcumin from the hydrophilic matrix gel; the release kinetic of curcumin changed from zero order to a Higuchi release profile. Overall, the developed nanoemulsion system not only improved curcumin permeability but also protected the curcumin from chemical degradation.

SDS-coated atovaquone nanosuspensions show improved therapeutic efficacy against experimental acquired and reactivated toxoplasmosis by improving passage of gastrointestinal and blood-brain barriers.

Toxoplasmic encephalitis (TE) is the most common clinical manifestation of reactivated infection with Toxoplasma gondii in immunocompromised patients that is lethal if untreated. The combination of pyrimethamine plus sulfadiazine or clindamycin is the standard therapy for the treatment of TE, but these combinations are associated with hematologic toxicity and/or life-threatening allergic reactions. Therefore, alternative treatment options are needed. Atovaquone is safe and highly effective against T. gondii in vitro, but the oral micronized solution shows poor bioavailability. We synthesized atovaquone nanosuspensions (ANSs) coated with poloxamer 188 (P188) and sodium dodecyl sulfate (SDS) to improve oral bioavailability and passage through the blood-brain barrier (BBB). Coating of ANSs with SDS resulted in enhanced oral bioavailability and enhanced brain uptake of atovaquone compared to Wellvone(®) in murine models of acute and reactivated toxoplasmosis as measured by high performance liquid chromatography (HPLC). Parasite loads and inflammatory changes in brains of mice treated with SDS-coated ANS were significantly reduced compared to untreated controls and to Wellvone(®)-treated mice. In conclusion, nanosuspensions coated with SDS may ultimately lead to improvements in the treatment of TE and other cerebral diseases.

The role of apolipoprotein E in uptake of atovaquone into the brain in murine acute and reactivated toxoplasmosis.

We investigated whether coating of atovaquone nanosuspensions (ANSs) with apolipoprotein E (apoE) peptides improves the uptake of atovaquone into the brain. The passage across the blood-brain barrier (BBB) of ANSs stabilized by polysorbate 80 (Tween 80), poloxamer 184 (P184), or poloxamer 338 (P338) and the same formulations coated with apoE peptides were analyzed in vitro and in vivo. Passage through a rat coculture model of the BBB did not differ between individual atovaquone formulations, and the addition of apoE peptides did not enhance the transport. Following the induction of toxoplasmic encephalitis (TE) in mice, treatment with all atovaquone formulations reduced the number of parasites and inflammatory foci compared with untreated mice. Uptake of atovaquone into the brain did not depend on coating with apoE. Finally, incubation of apoE peptide-coated ANSs with brain endothelial cells for 30 min did result in the accumulation of nanoparticles on the cell surface but not in their uptake into the cells. In conclusion, ANSs coated with Tween 80 or poloxamers showed therapeutic efficacy in murine toxoplasmosis. ApoE- and apoE-derived peptides do not induce the uptake of ANSs into the brain. Alternative mechanisms seem to be in operation, thereby mediating the passage of atovaquone across the BBB.