Sclareol (SC) is arousing great interest due to its cytostatic and cytotoxic activities in several cancer cell lines. However, its hydrophobicity is a limiting factor for its in vivo administration. One way to solve this problem is through nanoencapsulation. Therefore, solid lipid nanoparticles (SLN-SC) and nanostructured lipid carriers (NLC-SC) loaded with SC were produced and compared regarding their physicochemical properties. NLC-SC showed better SC encapsulation than SLN-SC and was chosen to be compared with free SC in human cancer cell lines (MDA-MB-231 and HCT-116). Free SC had slightly higher cytotoxicity than NLC-SC and produced subdiploid DNA content in both cell lines. On the other hand, NLC-SC led to subdiploid content in MDA-MB-231 cells and G2/M checkpoint arrest in HCT-116 cells. These findings suggest that SC encapsulation in NLC is a way to allow the in vivo administration of SC and might alter its biological properties

All-trans retinoic acid (ATRA) has been studied for the treatment of cancer, including leukemia and breast cancer. This work aims to develop nanoemulsions (NE) loaded with a hydrophobic ion pair (HIP) of all-trans retinoic acid (ATRA) and a lipophilic amine, stearylamine (SA), and coated with hyaluronic acid (HA) to enhance anticancer activity and reducing toxicity. Blank NE was prepared by spontaneous emulsification and optimized prior to HIP incorporation. NE-ATRA was electrostatically coated with different concentrations of HA. Incorporation of ATRA-SA led to monodisperse NE with small size (129 ± 2 nm; IP 0.18 ± 0.005) and positive zeta potential (35.7 ± 1.0 mV). After coating with 0.5 mg/mL HA solution, the mean diameter slightly increased to 158 ± 5 nm and zeta potential became negative (-19.7 ± 1.2 mV). As expected, high encapsulation efficiency (near 100%) was obtained, confirmed by polarized light microscopy and infrared analysis. Formulations remained stable over 60 days and release of ATRA from NE was delayed after the hydrophilic HA-coating. HA-coated NE-ATRA was more cytotoxic than free ATRA for MDA-MB-231 and MCF-7 breast cancer cell lines, especially in the CD44 overexpressing cells. Blank coated formulations showed no cytotoxicity. These findings suggest that this easily-made HA-coated NE-ATRA formulation is a promising alternative for parenteral administration, thus improving the breast cancer therapy with this drug.

Descrevem-se o efeito terapêutico e os eventos adversos associados com o uso tópico de paromomicina 10% em gel na leishmaniose cutânea. Quinze pacientes com leishmaniose cutânea cumpriram os critérios de inclusão descritos a seguir: contra-indicação para o uso de antimoniato de meglumina, intradermorreação de Montenegro positiva e até quatro lesões ulceradas. A fórmula foi prescrita duas vezes ao dia por 20 dias. Quatorze pacientes estiveram disponíveis para a avaliação do desfecho terapêutico e a proporção de cura foi de 21,4% (3/14), 50% melhoraram até a epitelização completa e a proporção de falha foi de 28,6%. Nove pacientes que não apresentaram cura inicialmente foram re-tratados. Oito receberam uma nova série de paromomicina tópica e um foi tratado com antimoniato de meglumina. Dois pacientes não receberam novo tratamento e tiveram melhora lenta e contínua. Cinco de oito pacientes retratados com paromomicina tópica alcançaram a cura clínica, e três apresentaram falha, incluindo um paciente que tinha apresentado melhora com o primeiro tratamento. Os eventos adversos foram leves e locais em 53,3% dos pacientes e nunca levaram à suspensão do tratamento.

The therapeutic effect of and adverse events associated with topical use of 10% paromomycin gel on cutaneous leishmaniasis are described. Fifteen patients with cutaneous leishmaniasis fulfilled the following inclusion criteria: contraindication for the use of meglumine antimoniate, positive Montenegro skin test and up to four ulcerated lesions. The formula was prescribed twice a day for 20 days. Fourteen patients were available for the therapeutic outcome evaluation. The cure rate was 21.4% (3/14); 50% improved as far as complete epithelialization; and the failure rate was 28.6%. Nine patients who did not initially present cure were retreated. Eight received a new series of topical paromomycin and one was treated with meglumine antimoniate. Two patients did not receive any new treatment and had continuous slow improvement. Five out of the eight patients retreated with topical paromomycin achieved clinical cure, and three presented failure, including one patient who had shown any improvement with the first treatment. For 53.3% of the patients, the adverse events were mild and local and never led to treatment suspension.

Pomadas contendo paromomicina (PA) são utilizadas no tratamento tópico da leishmaniose cutânea. Embora a influência do veículo seja crucial para otimização de formulações contendo PA, este aspecto não tem sido investigado experimentalmente. Neste estudo, nós avaliamos a influência do tipo de formulação [emulsões óleo-em-água (o/a), múltipla água-em-óleo-em-água (a/o/a) e pomadas] sobre a liberação e permeação cutânea in vitro da PA e os experimentos foram conduzidos sobre membranas de acetato de celulose e biópsias de pele de camundongos glabros, respectivamente. A liberação de PA a partir da emulsão o/a (51,7% da dose aplicada) foi mais rápida do que aquela observada a partir da emulsão múltipla a/o/a (3,0% da dose aplicada). A permeação cutânea da PA a partir da emulsão o/a (87,1% ± 3,9), através da pele sem estrato córneo, foi 5 a 6 vezes mais alta do que aquela observada para a emulsão múltipla a/o/a (14,7% ± 0,5) e pomada (16,6% ± 0.1), respectivamente. A permeação da PA através da pele normal foi desprezível para todas as formulações avaliadas. Nesta condição, a retenção cutânea a partir da emulsão o/a (0,9% ± 0,1) foi maior do que aquela observada para a emulsão múltipla (0,3% ± 0.1) e pomada. Esses resultados sugerem que um veículo hidrofílico seria uma alternativa interessante para aumentar o transporte e a permeação cutânea da PA.

Ointments containing paromomycin (PA) have been used for topical treatment of cutaneous leishmaniasis. Although influence of the vehicle on skin permeation is crucial for optimization of formulations containing PA, this aspect has not been investigated experimentally. In this study, we have evaluated the influence of the formulation type [oil-in-water (o/w), water-in-oil-in-water (w/o/w) emulsions and ointment] on in vitro release and skin permeation of PA and experiments were carried out on cellulose acetate membrane and skin biopsies from hairless mice, respectively. PA release from o/w emulsion (51.7% ± 0.9 of dose applied) was faster than that observed for w/o/w emulsion (3.0% ± 0.5). PA absorption from o/w emulsion (87.1% ± 3.9) through stripped skin was 5 to 6 times higher than that observed for w/o/w multiple emulsion (14.7% ± 0.5) and ointment (16.6% ± 0.1). PA permeation through intact (normal) skin was negligible for all tested formulations. Skin uptake from o/w emulsion (0.9% ± 0.1) was greater than that observed for w/o/w multiple emulsion (0.3% ± 0.1) and ointment (0.1% ± 0.1). These results suggest that a hydrophilic vehicle (o/w emulsion) could be an interesting alternative to improve topical delivery of PA.