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Besides their clinical application, chronic misuse of opioids has often been associated to drug addiction due to their addictive properties, underlying neuroadaptations of AMPA glutamate-receptor-dependent synaptic plasticity. Topiramate (TPM), an AMPAR antagonist, has been used to treat psychostimulants addiction, despite its harmful effects on memory. This study aimed to evaluate the effects of a novel topiramate nanosystem on molecular changes related to morphine reinstatement. Rats were previously exposed to morphine in conditioned place preference (CPP) paradigm and treated with topiramate-chitosan nanoparticles (TPM-CS-NP) or non-encapsulated topiramate in solution (S-TPM) during CPP extinction; following memory performance evaluation, they were re-exposed to morphine reinstatement. While morphine-CPP extinction was comparable among all experimental groups, TPM-CS-NP treatment prevented morphine reinstatement, preserving memory performance, which was impaired by both morphine-conditioning and S-TPM treatment. In the NAc, morphine increased D1R, D2R, D3R, DAT, GluA1 and MOR immunoreactivity. It also increased D1R, DAT, GluA1 and MOR in the dorsal hippocampus. TPM-CS-NP treatment decreased D1R, D3R and GluA1 and increased DAT in the NAc, decreasing GluA1 and increasing D2 and DAT in the dorsal hippocampus. Taken together, we may infer that TPM-CS-NP treatment was able to prevent the morphine reinstatement without memory impairment. Therefore, TPM-CS-NP may be considered an innovative therapeutic tool due to its property to prevent opioid reinstatement because it acts modifying both dopaminergic and glutamatergic neurotransmission, which are commonly related to morphine addiction.

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This study aimed to develop gel-creams from the lyophilised product of betamethasone dipropionate-loaded lipid-core nanocapsule suspensions and evaluated its efficacy in a model of contact dermatitis. The gel-creams were prepared and characterized followed by a study of in vitro drug penetration/permeation and its in vivo efficacy. The suspensions and lyophilised products showed nanometric size; the betamethasone content was 0.25 ± 0.01 mg/mL and the encapsulation efficiency was approximately 100%. The nanocapsules and redispersed powders presented control of the drug release. The gel-creams presented pH between 6.0-6.5 and exhibited non-Newtonian flow behavior, following the Herschel-Bulkley model. The skin penetration/permeation study indicated that betamethasone dipropionate can reach different skin layers. For in vivo efficacy, the contact dermatitis model was capable of causing tissue damage with changes in enzyme activities of the purinergic system in lymphocytes. The gel-creams showed the best dermatological and immunological efficacy and reduced oxidative damage in the evaluated tissues.

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In this work, hydrogels containing clotrimazole-loaded nanocapsules were developed through the innovative association of two mucoadhesive polymers: Pemulen® TR1 and Pullulan. Furthermore, the hydrogels macroscopic characteristics, pH and spreadability were evaluated. The formulations showed homogeneous appearance and pH compatible with vaginal application (around 5.0). Similar spreadability profiles were found in hydrogels containing clotrimazole-loaded nanocapsules and in the free drug as well. Hydrogels were evaluated considering their mucoadhesive potential by the falling liquid film method and the permeation/penetration capacity through cow vaginal mucosa in Franz cell. The results showed that the concentration of 3% Pullulan was important to increase the adhesive strength on the layer used (mucin gel or animal mucosa). The results of the permeation/penetration study showed that the hydrogel containing clotrimazole-loaded nanocapsules remained on the vaginal mucosa surface, what is ideal for the treatment of superficial vaginal infections. This way, the Pemulen/Pullulan blended hydrogel is a promising alternative for the treatment of vulvovaginal candidiasis.

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The association of vegetable products to nanostructured systems has attracted the attention of researchers due to several advantages, such as drug photoprotection, as well as the improvement of the pharmacological and therapeutic activities because of synergistic action, which can provide their topical application. In this work, lipid-core nanocapsules containing borage oil as oil core and betamethasone dipropionate were developed, and nanocapsules without the drug were prepared for comparison. The suspensions were characterized in relation to mean particle size, zeta potential, pH, drug content, and encapsulation efficiency. A photodegradation study was carried out and the in vitro release profile as well as the irritation potential of the drug after nanoencapsulation were also evaluated. In addition, the antiproliferative activity of the free borage oil as well as loaded in nanocapsules was studied. Lipid-core nanocapsules showed nanometric mean size (185-210 nm); polydispersity index below 0.10; negative zeta potential and pH slightly acid (6.0-6.2). Moreover, the drug content was close to theoretical concentration (0.50 +/- 0.03 mg/ml of betamethasone), and the encapsulation efficiency was approximately 100%. The study of the antiproliferative activity of borage oil showed ability to reduce cell growth of Allium cepa. The nanoencapsulation of betamethasone dipropionate provided greater protection against UVC light and decreased the irritation potential of the drug. The release profile of betamethasone dipropionate from nanocapsules followed monoexponential model.

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Onychomycosis are fungal infections affecting finger and toenails mainly caused by dermatophyte fungi and some Candida species. Low cure rates and frequent recurrence, development of a fungal resistance front to various antimicrobial agents topical and systemic, and an ineffective topical treatment make onychomycosis difficult to treat. Essential oils are excellent candidates for the topical treatment for onychomycosis because the development of resistance by fungi is rare, and the presence of side effects is low. They are composed of a complex variety of compounds, mainly terpenes, with low molecular weight, which may easily penetrate into the nail plate, finding the fungi elements. The complex mixture confers a broad antifungal spectrum of action, through interaction with biological membranes, interference in radical and enzymatic reaction of fungi cells. Essential oils may become the source of new therapeutic molecules, and the use of an essential oil incorporated into a topical formulation is an interesting, safe, and effective alternative for the treatment for onychomycosis. However, studies are needed to evaluate the efficacy of essential oils in the treatment for onychomycosis in vivo. This mini-review aims to present the potential use of essential oils for the treatment for onychomycosis, focusing on the last decade.

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In previous works, we developed nanocapsules and nanoemulsions containing the tea tree oil. The aim of this work was to prepare and characterize hydrogels containing these nanocarriers, and to evaluate their in vivo efficacy in protecting skin damage induced by UVB and cutaneous wound healing. Hydrogels were prepared using Carbopol Ultrez and their physicochemical characteristics were evaluated: macroscopic analysis, pH, spreadability and rheological properties. The in vivo antiedematogenic effect was evaluated by ear thickness measurement after UVB-irradiation. In order to evaluate healing action of hydrogels, we investigated the regression of the cutaneous lesion in rats. Hydrogels showed homogeneous aspect and pH values between 5.6-5.8 and a non-Newtonian behavior. The presence of nanocapsules and nanoemulsions in hydrogels did not change their spreadability profile. The inclusion of tea tree oil in the nanocapsules and nanoemulsions allowed reducing the edema induced by UVB exposure. Hydrogel containing nanocapsules presented a higher reduction of the wound area compared to the hydrogel containing nanoemulsions and hydrogel containing allantoin. This study shows the feasibility of obtained dermatological formulations containing the tea tree oil associated in nanostructured systems. These formulations represent a promising approach to topical treatment of inflammatory disorders and wound healing.

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