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Background: The skin, being the outermost layer of our body, is constantly exposed to oxidative stress induced by UV-radiation, pollutants, smoke and xenobiotics. To counteract the deleterious effects of such exposure, the skin is equipped with a complex anti-oxidation system, involving both exogenous and endogenous antioxidants. As low molecular weight antioxidants undergo depletion in counteracting oxidative stress occurring in the skin, topical supplementation with these agents is regarded as a suitable strategy to restore skin oxidative balance. Unfortunately, most antioxidants show unfavorable physico-chemical properties (e.g. excessive lipophilicity or hydrophilicity, chemical instability) that strongly limit their skin penetration and hence their effectiveness after topical application. To overcome these drawbacks, nanocarriers such as liposomes, niosomes, nanoemulsions and nanoparticles have been widely investigated as dermal delivery systems for antioxidants. Objective: The present paper will review two different types of lipid-based nanocarriers, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which represent the latest innovation in the field of nanoparticles designed as topical drug delivery systems. The effects of loading different topical antioxidants into SLN or NLC will be examined along with the usefulness of these antioxidant delivery systems in improving skin defenses against oxidative stress. Conclusion: In this review, recent studies regarding ability of solid lipid nanoparticles and nanostructured lipid carriers to improve dermal delivery of low molecular weight antioxidants have evidenced that these carriers show technological properties that make them particularly useful for topical delivery of antioxidants, both in pharmaceutical and cosmetic field.

Recent advances in nanotechnology have led to the development of nano-scale drugs and delivery systems to improve drug therapeutic effectiveness. Between the end of ′50 and the beginning of ′60, the first colloidal systems in the nano-metric range were achieved by chance. Several research highlighted the usefulness of these nano-carriers as drug delivery systems to overcome biological barriers later on. Since few drugs are effective after their topical application, due to the barrier function of the skin, colloidal systems have being widely explored as carriers to improve drug skin permeation. In particular, a great deal of attention has been paid to delivery systems based on highly biocompatible and biodegradable components such as lipids and phospholipids. As a result, different types of nano-carriers such as liposomes, microemulsions, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been developed. This review will focus on the nano-carriers arising from the first colloidal systems consisting of water, lipids and surfactants, i.e. microemulsions and their consequent improvement through the development of SLN and NLC. The properties of these nano-carriers will be discussed along with their applications as skin delivery systems both in pharmaceutical and cosmetic fields.

Intestinal microbiota is composed by a community of microorganisms, which regulate intestinal functions and affect the global health. It is presumable that the well-known intestinal damages induced by Non Steroidal Antiinflammatory Drugs (NSAIDs) mirror on the homeostasis of microbiota, as confirmed by studies investigating this aspect. This review reports the evolving knowledge in this field taking into account both intestinal damage and microbiota involvement. In addition, we analyze a recent study reporting how NSAIDs change intestinal bacterial composition and, on this basis, hypothesize further possible interactions. Indeed, NSAIDs are responsible for a marked reduction of Lactobacilli, which act in the maintenance of luminal pH, mucosal permeability, enterocyte adhesion, mucus production, and immune system modulation. Moreover, Bifidobacteria are involved in the modulation of intestinal motility and local immunity and the demonstrated dangerous effect of NSAIDs could operate through an interference with these functions. A participation of microbiota in mesalazine and salycilate prevention of intestinal cancer may be supposed through their ability to stimulate bacterial production of molecules interfering with cell cycle on the basis of scanty available data. Finally, a supplementation with probiotics in chronic users of NSAIDs may help microbiota remodeling in a damaged intestine, but the poor current knowledge does not allow setting a clear indication for their use despite few evidences of a beneficial effect. In conclusion, it is presumable that the multiple effects of NSAIDs on the lower gastro-intestinal tract may involve microbiota alterations and this consideration suggests further investigations.

The knowledge of the interactions between solid lipid nanoparticles (SLN) and cell membranes is important to develop effective carrier systems for drug delivery applications. Loading idebenone (IDE), an antioxidant drug useful in the treatment of neurodegenerative diseases, into SLN improves IDE antioxidant activity in in vitrobiological studies, but the mechanism by which IDE permeation through the blood–brain barrier (BBB) occurs are still unclear. Therefore, in this research, unloaded and IDE loaded SLN interaction with biomembrane models, consisting of dimyristoylphosphatidylcholine multilamellar vesicles (MLV), were studied by differential scanning calorimetry (DSC). In the experiments performed, unloaded and IDE loaded SLN where incubated with the biomembrane models and their interactions were evaluated through the variations in their calorimetric curves. The results of our DSC studies indicated that the SLN under investigation were able to go inside the phospholipid bilayers with a likely localization in the outer bilayers of the MLV from where they moved toward the inner layers by increasing the contact time between SLN and MLV. Furthermore, IDE loaded SLN were able to release IDE into the biomembrane model, thus facilitating IDE penetration into the bilayers while free IDE showed only a low ability to interact with this model of biomembranes. Our results suggest that these SLN could be regarded as a promising drug delivery system to improve IDE bioavailability and antioxidant activity.

Five indomethacin oligoethylene ester derivatives (3–7) were synthesized and evaluated for their anti‐inflammatory, analgesic, and ulcerogenic activity after oral administration. The molecular weight of the oligoethylene glycols used for synthesizing esters3–7ranged from 106 to 282. The chemical and enzymatic stabilities of esters3–7were evaluated in pH 7.4 and 2.0 buffers and in human plasma, respectively. All the prodrugs showed a good stability both in pH 7.4 phosphate buffer and in pH 2.0 buffer, and they were readily hydrolyzed by human plasma. Esters3–7showed an anti‐inflammatory activity, determined as the percent inhibition of carrageenan‐induced edema, similar to that of indomethacin, although at higher doses. From writhing test results, we observed that all the prodrugs exhibited better or similar analgesic activity compared to indomethacin. Esters3–7were significantly less irritating to the gastric mucosa than indomethacin, after oral administration, and esters3–5did not show any ulcerogenic activity, although they were administered at higher doses than indomethacin.

Purpose. To investigate the transport of a-tocopherol (T), tocopherol succinate (TS) and tocopherol succinate-3-glucose (a newly synthetized, less hydrophobic T ester; TSG) through bovine erythrocyte membranes.