pH stimulus-responsive hybrid nanoparticles: A system designed for follicular delivery of brazilian plant-derived 5-alpha-reductase enzyme inhibitors.

The 5-alpha-reductase enzyme, present in pilosebaceous units, plays a crucial role in the appearance of cutaneous hyperandrogenism manifestations (hirsutism, acne, and androgenetic alopecia). Its inhibition is an excellent strategy to reverse these conditions. Given the limitations of existing treatments, with transient effects and delayed therapeutic response, as well as the possibility of causing undesirable side effects, this study sought to develop new drug delivery systems to overcome these limitations. In other words, innovative stimuli-responsive hybrid nanoparticles were synthesized using silica/natural polysaccharides, encapsulating 5-alpha-reductase enzyme inhibitors derived from the plant Stryphnodendron adstringens (Mart.) Coville (commonly known as 'Barbatimão'). Silica core was synthesized by the modified Stöber method. The pH responsive polysaccharides used to coat the porous silica cores were chitosan, and sodium alginate, this coating was carried out using the Layer-by-Layer technique. The hybrid nanoparticles were characterized at molecular and physical-chemical levels. Furthermore, encapsulation efficiency, pH-dependent release behavior, and cytotoxicity were evaluated. Amorphous mesoporous structure with adequate size for follicular delivery (between 300 and 600 nm) in addition to effective phytocompound loading capacity, above 80 % was obtained. Based on the release studies, it was possible to observe pH responsiveness. The ethyl acetate fraction (EAF) obtained from "Barbatimão" bark extract was released in a controlled and more efficient manner by the alginate-coated nanoparticle (SNP_EAF_SA) at pH 7.4, which corresponds to the pH at the deepest area of hair follicles. Furthermore, SNP_EAF_SA proved to be less cytotoxic compared to EAF and chitosan-coated hybrid nanoparticles (SNP_EAF_CH). Characterization, release, and cytotoxicity results indicate that SNP_EAF_SA is a promising system for on-demand follicular delivery of antiandrogenic actives contained in EAF.

Skin interaction, permeation, and toxicity of silica nanoparticles: Challenges and recent therapeutic and cosmetic advances.

Silica nanoparticles (SNPs) received more attention with the emergence of nanotechnology with the aim and promise of becoming innovative drug delivery systems. They have been fulfilling this objective with excellence and nowadays they play a central role in biomedical applications. New SNPs application routes are being explored such as the epidermal, dermal, and transdermal routes. With that, novel models of synthesis, functionalization, and applications constantly appear. However, it is essential that such innovations are accompanied by in-depth studies on permeation, biodistribution, metabolization, and elimination of the generated by-products. Such studies are still incipient, if not rare. This article reviews significant findings on SNPs and their skin interactions. An extensive literature review on SNPs synthesis and functionalization methodologies was performed, as well as on the skin characteristics, skin permeation mechanisms, and in vivo toxicity assessments. Furthermore, studies of the past 5 years on the main therapeutic and cosmetic products employing SNPs, with greater emphasis on in vivo and ex vivo studies were included.