Current Pharmaceutical Design - Volume 25, Issue 21, 2019

Cosmeceuticals are innovative emerging health and beauty aid products that combine the benefits of cosmetic active ingredients and often innovative technological solutions of formulation and delivery. For decades, phytocompounds have been used in cosmetics as sunscreen, moisturizing, antiaging, and skin-based therapy. When compared to synthetic cosmetic ingredients, phytocompounds are generally milder, have a more favourable toxicity profile, and are biodegradable. The major concerns in the usage of phytocompounds are their low solubility, low penetration and physico-chemical instability when applied on the skin. To overcome these issues, different nanotechnology-based systems have been proposed and some of them are already on the market. Nanotechnologies can improve the solubility of poorly water-soluble compounds, facilitate skin permeation and increase their stability against light and temperature. Liposomes, solid lipid nanoparticles, transfersomes, ethosomes, nanostructured lipid carriers, and cyclodextrins are examples of nanotechnology-based systems currently in use to improve the performances of phytocompounds in skin care. This review focuses on cosmeceuticals that explore nanotechnology-based systems for the delivery of phytocompounds and emphasizes how these approaches can improve product performances with respect to conventional cosmetic formulations.

The skin and mucous membranes are subjected to many disorders and pathological conditions. Nature offers a wide range of molecules with antioxidant activity able to neutralize, at least in part, the formation of free radicals and therefore to counteract the phenomena of cellular aging. Since synthetic drugs for the treatment of skin diseases can induce resistance, it is particularly interesting to use compounds of plant origin, transporting them in pharmaceutical forms capable of controlling their release and absorption. This review provides an overview of new findings about the use of lipid-based nanosystems for the delivery of natural molecules useful on the topical treatment of skin disorders. Several natural molecules encapsulated in lipid nanosystems have been considered in the treatment of some skin pathologies or diseases. Particularly, the use of rosemary and eucalyptus essential oil, saffron derivatives, curcumin, eugenol, capsaicin, thymol and lycopene has been reported. The molecules have been alternatively encapsulated in viscous systems, such as the organogels, or in liquid systems, such as ethosomes, transferosomes, solid lipid nanoparticles and monoolein based dispersions thickened by inclusion in carbomer gels. The nanostructured forms have been in vitro and in vivo investigated for the treatment of skin disorders due to dehydration, inflammation, melanoma, wound healing, fungal infections or psoriasis. The data reported in the different studies have suggested that the cutaneous application of lipid nanosystems allows a deep interaction between lipid matrix and skin strata, promoting a prolonged release and efficacy of the loaded natural molecules. This review suggests that the application of natural molecules onto the skin by lipid-based nanosystems can provide numerous clinician benefits in dermatology and cosmetics.

Ethosomes are nanovesicular carriers for dermal administration. Phospholipids, ethanol at relatively high concentrations (up to 50%) and water are their main components. Ethosomes are what we call “soft vesicles” with fluid bilayers due to the presence of ethanol. The composition and structure of the vesicles augment their ability to entrap molecules with various physicochemical properties and deliver them to the deep strata of skin. Since their first design, ethosomal systems have been extensively investigated for a wide range of applications. This review focuses on work carried out in vitro, in vivo in animal models and in humans in clinical studies, with ethosomal formulations containing natural active molecules for the treatment of skin disorders. Skin bacterial and fungal infections, skin inflammation, acne vulgaris, arthritis, and skin cancer are examples of disorders managed successfully by ethosomal systems. Furthermore, Ethosomes loaded with a number of naturally occurring compounds for cosmetic applications are also reported. The efficient treatments together with a good safety profile and lack of toxicity or irritation paved the way towards the development of new dermal therapies.

Rheology, the study of the flow and deformation of matter, can be a daunting subject for scientists new to this field. However, its importance in characterization and optimization of formulations is indisputable. This review intends to provide basic and practical rheological notions in order to better understand the key concepts such as shear stress, shear rate, viscosity, elastic and viscous moduli and phase angle, and learn to distinguish between flow and oscillation experiments. We will explain the different rheological behaviors such as shear thinning, thixotropy or viscoelasticity. Throughout this review, these concepts will be illustrated with examples taken from pharmaceutical and cosmetic formulations. Rheology is a broad subject and this review does not intend to be comprehensive, but rather to be concise and pedagogical.

Starting from the second half of the 1900s, the advent of nanotechnology in medicine has provoked a profound revolution in this area; at present, nanomedicine delivered a remarkably large set of research and clinically useful tools as diagnostic devices, contrast agents, analytical tools, physical therapy applications, and drugdelivery vehicles. Concerning nanoformulations for drug delivery, they are constituted by nanoparticles with dimensions lower than 1 μm, usually characterized by improved pharmacokinetics, taking advantage of specific targeting, and reduced side effects. The contributors to the present chapter are reviewing a range of papers related to the structural characterization of nanoformulations by X-ray diffraction techniques. The whole of the considered papers underlines the essential role that biophysical techniques have acquired as an essential prerequisite to understanding stability, bioavailability, and lipid, biopolymer, and drug organization in nanoformulations.

Background: Microglia play a pivotal role in maintaining homeostasis in complex brain environment. They first exist as amoeboid microglial cells (AMCs) in the developing brain, but with brain maturation, they transform into ramified microglial cells (RMCs). In pathological conditions, microglia are activated and have been classified into M1 and M2 phenotypes. The roles of AMCs, RMCs and M1/M2 microglia phenotypes especially in pathological conditions have been the focus of many recent studies. Methods: Here, we review the early development of the AMCs and RMCs and discuss their specific functions with reference to their anatomic locations, immunochemical coding etc. M1 and M2 microglia phenotypes in different neuropathological conditions are also reviewed. Results: Activated microglia are engaged in phagocytosis, production of proinflammatory mediators, trophic factors and synaptogenesis etc. Prolonged microglia activation, however, can cause damage to neurons and oligodendrocytes. The M1 and M2 phenotypes featured prominently in pathological conditions are discussed in depth. Experimental evidence suggests that microglia phenotype is being modulated by multiple factors including external and internal stimuli, local demands, epigenetic regulation, and herbal compounds. Conclusion: Prevailing views converge that M2 polarization is neuroprotective. Thus, proper therapeutic designs including the use of anti-inflammatory drugs, herbal agents may be beneficial in suppression of microglial activation, especially M1 phenotype, for amelioration of neuroinflammation in different neuropathological conditions. Finally, recent development of radioligands targeting 18 kDa translocator protein (TSPO) in activated microglia may hold great promises clinically for early detection of brain lesion with the positron emission tomography.

Background: Maintaining the exposure of tacrolimus (Tac) after kidney transplantation (KT) must be necessary to prevent acute rejection (AR) and improve graft survival#140;but there is still no clear consensus on the optimal Tac target blood concentration and concentration-effect relationship is poorly defined. Methods: We conducted a dose-response meta-analysis to quantitatively assess the association between Tac blood concentration and (AR) or adverse effects after KT. A comprehensive search of PubMed, Embase and Cochrane library databases was conducted to find eligible studies up to 10th September 2018. Unpublished data from patients receiving KT in West China Hospital (Sichuan University, China) were also collected. Both twostage dose-response and one-stage dose-response meta-analysis models were used to improve the statistical power. Results: A total of 4967 individuals from 10 original studies and 1453 individuals from West China Hospital were eligible for the ultimate analysis. In the two-stage dose-response meta-analysis model, we observed a significant non-linear relationship between Tac blood concentration and AR (P < 0.001) with moderate heterogeneity (I2 = 46.0%, P = 0.08). Tac blood concentration at 8ng/ml was associated with the lowest risk of AR (RR: 0.26, 95%CI: 0.13 - 0.54) by reference to 2ng/ml. Tac concentration at 7.0 - 11.0 ng/ml reduced the risk of AR by at least 70%, 5-14 ng/ml by at least 60%, and 4.5 – 14 ng/ml at least 50%. In the one-stage dose-response model, we also found a strong non-linear relationship between Tac and AR (P < 0.001) with moderate heterogeneity (I2 = 41.2%, P = 0.10). Tac concentration of 7.5 ng/ml was associated with the lowest risk of AR (RR: 0.35, 95%CI: 0.16 - 0.77). The blood concentration at 5.5 - 9.5 ng/ml was associated with the reduced AR by at least 60% and 4.5 - 10.5 ng/ml by at least 50% by reference to 2 ng/ml. Conclusion: Maintaining Tac blood concentration at 5 - 9.5 ng/ml within the first year may prevent AR most effectively.