Evaluation of a multiple microemulsion from Trichilia catigua extract and the percutaneous penetration through skin by Phase-Resolved photoacoustic spectroscopy.

Emulsion systems have been a breakthrough in cosmetic products, providing performance and effectiveness of products that use this technological strategy for drug delivery systems. In this sense, the microemulsion of the multiple emulsion W/O/W type containing a standardized extract of Trichilia catigua with high levels of polyphenols and antioxidants has great potential for cosmetic use. The aim of this study was to evaluate the formulations safety through the analysis of toxicity, comedogenicity, and histopathology in rabbits and apply the Phase-Resolved Photoacoustic Spectroscopy method to determine the formulation percutaneous penetration through the skin. The ex vivo experiments were performed in the ears of albino New Zealand rabbits treated twice a day for 14 days. The results of histological, hematological, and blood chemistry showed that the formulations are safe. Histopathological analysis showed no tissue reaction in any of the analyzed organs (liver and kidneys), confirming the absence of toxicity. Histological analysis showed that the formulations with extract of T. catigua demonstrated mild-moderately comedogenic and acanthosis compared to the control group. Inflammatory reactions, erythema, and desquamation were not observed in treated and controls animals. The phase-resolved photoacoustic spectroscopy method showed the penetration of the developed formulations throughout the rabbit's skin, identifying their absorption bands at the dermal side of the skin. In conclusion, the results of this study provide a step towards the application of the developed natural antioxidant encapsulated in a multiple microemulsion for skincare, concerned with the physical, chemical, and biological properties of the formulation.

The importance of the relationship between mechanical analyses and rheometry of mucoadhesive thermoresponsive polymeric materials for biomedical applications.

Pluronic F127® was associated with a carbomer homopolymer type B, as a model polymer blend to evidence the information provided by rheological and mechanical analyses on the development of bioadhesive thermoresponsive systems. The mechanical analysis enabled to observe that 20% (w/w) Pluronic F127®-polymer blends were harder, more adhesive, more mucoadhesive, more compressive and less soft. In addition, continuous flow rheometry demonstrated that the systems were plastic with rheopexy (15%, w/w, Pluronic F127®) or thixotropic (20%, w/w, Pluronic F127®). Oscillatory rheometry exhibited the increase of temperature, and the polymeric concentration increases the elasticity of the formulations. Moreover, correlation index showed that softness and textural analysis can be correlated and complementary, whereas adhesiveness cannot be correlated to mucoadhesion and is less specific. Rheological interaction parameter and gelation temperature showed that 15/0.25-polymer blend is suitable for pharmaceutical and biomedical application, since it can be administered in the liquid form and be gelled in the application site with proper mucoadhesion that can suggest an improved clinical efficacy. Therefore, the mechanical and rheological analyses are useful to characterize and select the best bioadhesive thermoresponsive formulation for the proposed treatment with improved performance.

Nanocarriers for photodynamic therapy-rational formulation design and medium-scale manufacture.

The development and manufacture of novel nanocarriers for drug delivery has proved challenging with regards to scale-up and pharmaceutical quality. Polymeric nanocarriers composed of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) were prepared and the photosensitizer meso-tetrakis(3-hydroxyphenyl) chlorin (mTHPC) was effectively encapsulated. Furthermore, the interplay of various process and formulation parameters and their impact on the most important product specifications were investigated by using a factorial design and a central composite design in a microfluidic manufacturing process. These nanoparticles for intravenous administration with a size of 97 ± 0.13 nm, narrow size distribution, and an encapsulation efficiency of more than 80% were produced at high throughput. In vitro stability and in vitro drug release testing were applied for quality control purposes. Finally, the toxicity of the photosensitizer was tested in vitro. The cytotoxicity was successfully reduced while the efficacy of the formulation was maintained. First observations using in vivo imaging suggest effective distribution of the nanocarrier system after injection into rodents. Thus, further in vivo testing of the beneficial effects of nanoencapsulation into the matrix system and its formulation will be considered for the delivery of mTHPC to tumor tissues during photodynamic therapy.