Penetration of Quantum Dot Particles Through Human Skin

The skin is a large and accessible area of the body, offering the possibility to be used as an alternative route for drug delivery. In the last few years strong progress has been made on the developing of nanoparticulate systems for specific applications. The interaction of such small particles with human skin and their possible penetration attracted some interest from toxicological as well as from drug delivery perspectives. As size is assumed to play a key role, the aim of the present work was to investigate the penetration profile of very small model particles (similar to 4 nm) into excised human skin under conditions chosen to mimic the in vivo situation. Possible application procedures such as massaging the formulation (5 to 10 minutes) were analyzed by non-invasive multiphoton- and confocal laser scanning microscopy (MPM, CLSM). Furthermore, the application on damaged skin was taken into account by deliberately removing parts of the stratum corneum. Although it was clearly observed that the mechanical actions affected the distribution pattern of the QDs on the skin surface, there was no evidence of penetration into the skin in all cases tested. QDs could be found in deeper layers only after massaging of damaged skin for 10 min. Taking these data into account, obtained on the gold standard human skin, the potential applications of nanoparticulate systems to act as carrier delivering drugs into intact skin might be limited and are only of interest for partly damaged skin.

Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage. Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution. Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.