Nanocarriers for Skin Applications: Where Do We Stand?

Skin penetration of active molecules for treatment of diverse diseases is a major field of research owing to the advantages associated with the skin like easy accessibility, reduced systemic-derived side effects, and increased therapeutic efficacy. Despite these advantages, dermal drug delivery is generally challenging due to the low skin permeability of therapeutics. Although various methods have been developed to improve skin penetration and permeation of therapeutics, they are usually aggressive and could lead to irreversible damage to the stratum corneum. Nanosized carrier systems represent an alternative approach for current technologies, with minimal damage to the natural barrier function of skin. In this Review, the use of nanoparticles to deliver drug molecules, genetic material, and vaccines into the skin is discussed. In addition, nanotoxicology studies and the recent clinical development of nanoparticles are highlighted to shed light on their potential to undergo market translation.

Environmental Liquid Cell Technique for Improved Electron Microscopic Imaging of Soft Matter in Solution.

Liquid-phase transmission electron microscopy is a technique for simultaneous imaging of the structure and dynamics of specimens in a liquid environment. The conventional sample geometry consists of a liquid layer tightly sandwiched between two Si3N4 windows with a nominal spacing on the order of 0.5 µm. We describe a variation of the conventional approach, wherein the Si3N4 windows are separated by a 10-µm-thick spacer, thus providing room for gas flow inside the liquid specimen enclosure. Adjusting the pressure and flow speed of humid air inside this environmental liquid cell (ELC) creates a stable liquid layer of controllable thickness on the bottom window, thus facilitating high-resolution observations of low mass-thickness contrast objects at low electron doses. We demonstrate controllable liquid thicknesses in the range 160 ± 34 to 340 ± 71 nm resulting in corresponding edge resolutions of 0.8 ± 0.06 to 1.7 ± 0.8 nm as measured for immersed gold nanoparticles. Liquid layer thickness 40 ± 8 nm allowed imaging of low-contrast polystyrene particles. Hydration effects in the ELC have been studied using poly-N-isopropylacrylamide nanogels with a silica core. Therefore, ELC can be a suitable tool for in situ investigations of liquid specimens.

Semi-interpenetrated, dendritic, dual-responsive nanogels with cytochrome c corona induce controlled apoptosis in HeLa cells.

The use of thermoresponsive nanogels (NGs) allows the controlled release of therapeutic molecules upon a thermal switch. Usually, this strategy involves the use of temperature increase to activate cargo expulsion from shrinking NGs. In this study, poly(N-isopropylacrylamide) (pNIPAM)-based NGs were involved in the release of a therapeutic protein corona by temperature decrease. NGs based on dendritic polyglycerol (dPG) and thermoresponsive pNIPAM were semi-interpenetrated with poly(4-acryloylamine-4-(carboxyethyl)heptanodioic acid) (pABC). The resulting semi-interpenetrated NGs retain the thermoresponsive properties of pNIPAM, together with pH-responsive, dendritic pABC as a secondary network, in one single nanoparticle. Semi-interpenetrated polymer network (SIPN) NGs are stable in physiological conditions, exhibit a reversible phase transition at 35 °C, together with tunable electrophoretic mobilities around the body temperature. The binding of cytochrome c (cyt c) was successful on SIPN NGs in their collapsed state at 37 °C. Upon cooling of the samples to room temperature, the swelling of the NG effectively boosted the release of cyt c, as compared with the same kept at constant 37 °C. These responsive SIPN NGs were able to deliver cyt c to cancer cells and specifically induce apoptosis at 30 °C, while the cells remained largely unaffected at 37 °C. In this way, we show therapeutic efficacy of thermoresponsive NGs as protein carriers and their efficacy triggered by temperature decrease. We envision the use of such thermal trigger as relevant for the treatment of superficial tumors, in which induction of apoptosis can be controlled by the application of local cooling agents.