Silas Arandas Monteiro e Silva

Transcorneal iontophoresis of dendrimers: PAMAM corneal penetration and dexamethasone delivery

Iontophoresis of nanocarriers in the eye has been proposed to sustain drug delivery and maintain therapeutic concentrations. Fourth generation polyamidoamine (PAMAM) dendrimers are semi-rigid nanoparticles with surface groups that are easily modified. These dendrimers are known to modulate tight junctions, increase paracellular transport of small molecules and be translocated across epithelial barriers, exhibiting high uptake by different cell lines. The first aim of this study was to investigate the effect of iontophoresis on PAMAM penetration and distribution into the cornea. The second aim was to evaluate, ex vivo and in vivo, the effect of these dendrimers in dexamethasone (Dex) transcorneal iontophoresis. Anionic (PAMAM G3.5) and cationic (PAMAM G4) dendrimers were labeled with fluorescein isothiocyanate (FITC), and their distribution in the cornea was investigated using confocal microscopy after ex vivo anodal and cathodal iontophoresis for various application times. The particle size distribution and zeta potential of the dendrimers in an isosmotic solution were determined using dynamic light scattering and Nanoparticle Tracking Analysis (NTA), where the movement of small particles and the formation of large aggregates, from 5 to 100 nm, could be observed. Transcorneal iontophoresis increased the intensity and depth of PAMAM-FITC fluorescence in the cornea, suggesting improved transport of the dendrimers across the epithelium toward the stroma. PAMAM complexes with Dex were characterized by (13)C-NMR, (1)H-NMR and DOSY. PAMAM G3.5 and PAMAM G4 increased the aqueous solubility of Dex by 10.3 and 3.9-fold, respectively; however, the particle size distribution and zeta potential remained unchanged. PAMAM G3.5 decreased the Dex diffusion coefficient 48-fold compared with PAMAM G4. The ex vivo studies showed that iontophoresis increased the amount of Dex that penetrated into the cornea by 2.9, 5.6 and 3.0-fold for Dex, Dex-PAMAM G4 and Dex-PAMAM G3.5, respectively. In vivo experiments, however, revealed that iontophoresis of Dex-PAMAM-G3.5 increased Dex concentration in the aqueous humor by 6.6-fold, while iontophoresis of Dex-PAMAM G4 and Dex increased it 2.5 and 2-fold, respectively. Therefore, iontophoresis targeted PAMAM to the cornea but it is the sustained delivery of the Dex from PAMAM that prevents its rapid elimination from the aqueous humor. In conclusion, iontophoresis of PAMAM complexes represents a promising strategy for targeted and sustained topical drug delivery to the eye.

Minimum Evaporation Model of Dermatological Delivery Systems. Lamellar Liquid Crystal Formulations Containing Brazilian Nut (Bertholletia excelsa HBK) Vegetable Oil and Guarana Glycolic Extract

Formulations with lyotropic liquid crystals were prepared from a Brazilian nut vegetable oil, guarana extract and combination of sorbitan monooleate (Span 80) and sorbitan monolaurate ethoxylate EO 20 (Tween 20) in the ratio 1:3 (surfactant component) and their physical–chemical aspects and rheological properties were determined. Compositions with liquid crystals were found in the pseudoternary diagram in a surfactant range of 70–90% and polarized light microscopy, small-angle x-ray scattering (SAXS) showed them to be lamellar. The preparations were furthermore characterized rheologically by shear stress shear rate sweeps finding plastic and pseudoplastic behavior without thixotropy. Electric conductivity and pH measurements demonstrated a potential for future application as dermatological delivery system of the active compounds in the Bertholletia excelsa and Paullinia cupana.

An overview about oxidation in clinical practice of skin aging

Free radicals are unstable chemical species, highly reactive, being formed by cellular entities of different tissues. Increased production of these species without proper effective action of endogenous and exogenous antioxidant systems, generates a condition of oxidative stress, potentially provider of skin disorders that extend from functional impairments (skin cancer, dermatitis, chronic and acute inflammatory processes) even aesthetic character, with the destruction of structural proteins and cellular changes with the appearance of stains, marks and lines of expressions and other signs inherent to the intrinsic and extrinsic skin aging process. The antioxidants are chemical substances commonly used in clinical practice for topical application and may contribute in the fight against the radical species responsible for many skin damage. This paper summarized the main evidence of the benefits brought by the topical application of antioxidants in the skin, considering the amplitude of the indicative performance of antioxidant activity by in vitro and ex-vivo tests as well as in vivo tests. It is recognized that a breadth of product performance tests should be explored to truly identify the effectiveness of antioxidant products for an anti-aging effect.

Development of nanotechnology-based drug delivery systems with olive vegetable oil for cutaneous application

Liquid-Crystalline Systems represent active compounds delivery systems that may be able to overcome the physical barrier of the skin, especially represented by the stratum corneum. To obtain these systems, aqueous and oily components are used with surfactants. Of the different association structures in such systems, the liquid-crystalline offer numerous advantages to a topical product. This manuscript presents the development of liquid-crystalline systems consisting, in which the oil component is olive oil, its rheological characterizations, and the location of liquid crystals in its phase map. Cytotoxic effects were evaluated using J-774 mouse macrophages as the cellular model. A phase diagram to mix three components with different proportions was constructed. Two liquid crystalline areas were found with olive oil in different regions in the ternary diagram with two nonionic surfactants, called SLC1 (S1) and SLC2 (S2). These systems showed lamellar liquid crystals that remained stable during the entire analysis time. The systems were also characterized rheologically with pseudoplastic behavior without thixotropy. The texture and bioadhesion assays showed that formulations were similar statistically (p < 0.05), indicating that the increased amount of water in S2 did not interfere with the bioadhesive properties of the systems. In vitro cytotoxic assays showed that formulations did not present cytotoxicity. Olive oil-based systems may be a promising platform for skin delivery of drugs.

Gallic Acid-Loaded Gel Formulation Combats Skin Oxidative Stress: Development, Characterization and Ex Vivo Biological Assays

Oxidative stress, which is a result of overproduction and accumulation of free radicals, is the main cause of several skin degenerative diseases, such as aging. Polyphenols, such as gallic acid, are an important class of naturally occurring antioxidants. They have emerged as strong antioxidants that can be used as active cosmetics. The purpose of this study was to develop a gallic acid-loaded cosmetic gel formulation and characterize it using rheological, mechanical, and bioadhesive tests. Its antioxidant effect in the stratum corneum was evaluated by a non-invasive method. According to the characterization tests, the formulation exhibited skin adhesiveness and pseudoplastic behavior without thixotropy, rendering it suitable for use as a cosmetic formulation. Furthermore, the non-invasive method indicated the antioxidant effect in the stratum corneum, with the global lipid peroxide reduction being 33.97 ± 11.66%. Thus, we were able to develop a promising gallic acid-loaded gel formulation that could reduce lipid peroxides and thus combat skin oxidative stress.

Formulations with green clay for acne-prone skin: evaluation of rheology and sensory: Formulações com argila verde para pele acneica: avaliação da reologia e do sensorial

Acne is an inflammatory skin condition that develops in pilosebaceous follicles, affecting mainly the onset of puberty. Among the numerous chemicals with dermatological and cosmetic purpose, traded and prescribed, raw materials of mineral origin have been often sought in formulations aimed at treating and / or preventing acne. This work aimed at the development of cosmetic preparations including green clay and sensory analysis of the formulations. Four formulations containing 2.5 % to 5 % green clay, in the presence or absence of dimethicone were prepared. The rheological behavior of the samples was analyzed at time 0, 24 hours, 30 days, 60 days and 90 days, using a cone and plate type rheometer (DVII + viscometer, Brookfiel). Sensory analyses of the formulations were also made. It can be concluded that all formulations exhibited pseudoplastic behavior and, through statistical analysis, it was found that there were no significant differences in acceptance between the formulations with or without dimethicone in the attributes of spreadability, stickiness, color and sensation after application. However, in regard to the attribute of odor, it was found that there was a greater acceptance in formulations to which dimethicone was added.