No abstract

: Administration of substances through the skin represents a promising alternative, in relation to others drug administration routes, due to its large body surface area, in order to offer ideal and multiple sites for drug administration. In addition, the administration of drugs through the skin avoids first-pass metabolism, allowing an increase in the bioavailability of drugs, as well as reducing their side effects. However, the stratum corneum (SC) comprises the main barrier of protection against external agents, mainly due to its structure, composition and physicochemical properties, becoming the main limitation for the administration of substances through the skin. In view of the above, pharmaceutical technology has allowed the development of multiple drug delivery systems (DDS), which include liquid crystals (LC), cubosomes, liposomes, polymeric nanoparticles (PNP), nanoemulsions (NE), as well as cyclodextrins (CD) and dendrimers (DND). It appears that the DDS circumvents the problems of drug absorption through the SC layer of the skin, ensuring the release of the drug, as well as optimizing the therapeutic effect local. This review aims to highlight the DDS that include LC, cubosomes, lipid systems, PNP, as well as CD and DND, to optimize topical skin therapies.

: Pancreatic Ductal Adenocarcinoma (PDA) is a highly metastatic tumor, and the liver is the first target, which restricts the use of medications. PDA is considered one of the most aggressive types of cancer in the world, with extremely short survival time, depending on the stage of diagnosis. In non-surgical cases, chemotherapy alternatives are only effective in 40% to 60% of patients. The low efficiency of treatments occurs mainly due to the complex microenvironment in PDA leading to chemoresistance to treatments and makes it difficult to access the drug. A very important histological characteristic of PDA is the extremely dense stroma, which leads to low vascularization of tumor tissue. Consequently, stroma environment causes less drug accumulation in tumor cells, even selective and/or targeted drugs. Overcoming the stroma's microenvironment is a major challenge for effective therapies that manage to get through this difficult access. Moreover, specific genes lead to direct chemoresistance of PDA, due to their high progression. In this scenario, nanotechnology appears as an alternative to overcome these clinical challenges that must be overcome concern two distinct ways: the stroma and the tumor properly. Thus, this review aimed to bring advances in the application of nanotechnology aiming to open up new landscapes against PDA. There are a huge number of nanoparticles carrying drugs in preclinical and clinical trials for the effective treatment of PDA. These works were discussed and it was proposed, based on the current scenario, the future prospects for an efficient treatment of PDA.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of their characteristics are low toxicity, biodegradability, and biocompatibility. They are divided into α‐, β‐, and γ‐cyclodextrins, each with its own particularities. They can undergo surface modifications to improve their performances. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading, and others. Cyclodextrins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles, and suppositories) and allow better topical biological effects of drugs at administration sites such as skin, eyeballs, and oral, nasal, vaginal, and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other administration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles and the in vivo hearing system integrity evaluated to certify that they will be safe and will not cause hearing loss.

Aim: Octyl gallate (OG) loaded into a nanostructured lipid system (NLS) was tested for antifungal activity and in vitro and in vivo toxicity. Methods & Results: The features of NLS-OG were analyzed by dynamic light scattering and showed adequate size (132.1 nm) and homogeneity (polydispersity index = 0.200). OG was active against Paraccoccidioides spp., and NLS-OG did not affect antifungal activity. NLS-OG demonstrated reduced toxicity to lung cells and zebrafish embryos compared with OG, whereas NLS was toxic to hepatic cells. OG and NLS-OG did not show toxicity in a Galleria mellonella model at 20 mg/kg. All toxic concentrations were superior to MIC (antifungal activity). Conclusion: These results indicate good anti- Paracoccidioides activity and low toxicity of NLS-OG.