Alpha-tocopheryl succinate improves encapsulation, pH-sensitivity, antitumor activity and reduces toxicity of doxorubicin-loaded liposomes.

Doxorubicin (DOX) plays an important role in cancer treatment; however, high cardiotoxicity and low penetration in solid tumors are the main limitations of its use. Liposomal formulations have been developed to attenuate the DOX toxicity, but the technological enhancement of the liposomal formulation as well as the addition of another agent with antitumor properties, like alpha-tocopheryl succinate (TS), a semi-synthetic analog of vitamin E, could certainly bring benefits. Thus, in this study, it was proposed the development of liposomes composed of DOX and TS (pHSL-TS-DOX). A new DOX encapsulation method, without using the classic ammonium sulfate gradient with high encapsulation percentage was developed. Analysis of Small Angle X-ray Scattering (SAXS) and release study proved the pH-sensitivity of the developed formulation. It was observed stabilization of tumor growth using pHSL-TS-DOX when compared to free DOX. The toxicity tests showed the safety of this formulation since it allowed body weight initial recovery after the treatment and harmless to heart and liver, main target organs of DOX toxicity. The developed formulation also avoided the occurrence of myelosuppression, a typical adverse effect of DOX. Therefore, pHSL-TS-DOX is a promising alternative for the treatment of breast cancer since it has adequate antitumor activity and a safe toxicity profile.

Comedolytic effect and reduced skin irritation of a new formulation of all-trans retinoic acid-loaded solid lipid nanoparticles for topical treatment of acne.

Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.

Preparação e caracterização de extratos glicólicos enriquecidos em taninos a partir das cascas de Stryphnodendron adstringens (Mart. ) Coville (Barbatimão) / Preparation and characterization of propylene glicol extracts obtained from dried stem barks of Stryphnodendron adstringens (Mart. ) Coville (barbatimão)

Neste estudo, foram preparados e caracterizados extratos glicólicos de cascas de Stryphnodendron adstringens (barbatimão), visando a obtenção de extratos enriquecidos em taninos. Os extratos foram preparados, em triplicata, por meio de maceração estática da droga vegetal pulverizada, seguida de percolação, com diferentes misturas de 90 por cento (PGL90), 80 por cento (PGL80) e 70 por cento (PGL70) de propilenoglicol em água. Os extratos foram recolhidos de forma fracionada. Cada fração obtida foi submetida a análises de pH, densidade, determinação de resíduo seco, e dos teores de taninos e de polifenóis. Os resultados dessas análises demonstraram que o solvente PGL70 extraiu maior quantidade de constituintes químicos da droga vegetal, a partir das primeiras frações. No entanto, as análises revelaram que o solvente PGL80 foi mais seletivo ao extrair, especificamente, os taninos da planta. Os resultados indicaram que a incorporação de 20 por cento de água ao propilenoglicol deve conduzir a extratos mais enriquecidos em taninos, a partir das cascas de barbatimão.

Extracts from dried stem barks of Stryphnodendron adstringens (barbatimão) were prepared with 90 percent, 80 percent and 70 percent of propylene glycol and water (PGL90, PGL80 and PGL70, respectively). The extract was prepared by percolation and collected as fractions of 100mL. The pH, density, dry residue and tannin and polyphenolic contents were determined for each fraction. The results showed that the extraction of chemical compounds was more efficient with PGL70, but PGL80 was more selective for extraction of tannins, the active compounds.