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In the present work, the preparation, characterization and therapeutic potential of baicalin-loaded nanohydrogels are reported. The nanohydrogels were prepared by sonicating (S nanohydrogel) or autoclaving (A nanohydrogel) a dispersion of cholesterol-derivatized gellan in phosphate buffer. The nanohydrogel obtained by autoclave treatment showed the most promising results: smaller particles (∼362 nm vs. ∼530 nm), higher homogeneity (polydispersity index = ∼0.24 vs. ∼0.47), and lower viscosity than those obtained by sonication. In vitro studies demonstrated the ability of the nanohydrogels to favour the deposition of baicalin in the epidermis. A high biocompatibility was found for baicalin-loaded nanohydrogels, along with a great ability to counteract the toxic effect induced by hydrogen peroxide in cells, as the nanohydrogels re-established the normal conditions (∼100% viability). Further, the potential of baicalin-loaded nanohydrogels in skin wound healing was demonstrated in vivo in mice by complete skin restoration and inhibition of specific inflammatory markers (i.e., myeloperoxidase, tumor necrosis factor-α, and oedema)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70nm in diameter, while PEVs were larger (∼170nm). The presence of propylene glycol or glycerol increased the viscosity of the vesicle systems, positively affecting their stability. The ability of the vesicles to promote the accumulation of the phenols (especially gallic acid) in the skin was demonstrated, as well as their low toxicity and great ability to protect keratinocytes and fibroblasts from oxidative damage. Additionally, an improvement of the antimicrobial activity of the phenols was shown against different skin pathogens. The co-loading of resveratrol and gallic acid in modified phospholipid vesicles represents an innovative, bifunctional tool for preventing and treating skin affections., (Copyright © 2017 Elsevier B.V. All rights reserved.)

This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to increase their stability, led to a reduction of vesicle size and a good homogeneity of the systems, after simple rehydration with water. X-ray diffraction study demonstrated that after the freeze-drying process, curcumin remained successfully incorporated within the vesicles. All the vesicles displayed similar features: size ranging from 220 to 287nm, spherical or oval shape, multilamellar or large unilamellar morphology with a peculiar multicompartment organization involving 1-4 smaller vesicles inside. In vitro studies demonstrated the ability of the combined polymers to protect the vesicles from the harsh conditions of the gastro-intestinal tract (i.e., ionic strength and pH variation), which was confirmed in vivo by the greater deposition of curcumin in the intestinal region, as compared to the free drug in dispersion. This enhanced accumulation of curcumin provided by the eudragit-hyaluronan immobilized vesicles, together with an increase in Caco-2 cell viability exposed to hydrogen peroxide, indicated that vesicles can ensure a local protection against oxidative stress and an increase in its intestinal absorption., (Copyright © 2016 Elsevier B.V. All rights reserved.)

New biocarriers, named santosomes, were formulated using Santolina insularis essential oil and hydrogenated phosphatidylcholine. They were modified by adding propylene glycol, a hydrophylic penetration enhancer, and loaded with phycocyanin, a protein found in cyanobacteria, which possesses antioxidant and antiinflammatory properties. The essential oil was expected to modify the bilayer structure and improve the delivery and efficacy of the protein due to a synergistic effect of the phospholipid and S. insularis terpenes. Santosomes were small in size (∼118nm), unilamellar and with polyhedral shape. SAXS patterns showed that phycocyanin strongly interacted with the polar heads of the vesicle bilayer. Phycocyanin-loaded vesicles did not show any toxic effect in vitro: cell viability was ∼100% in endothelial cells and ∼120% in keratinocytes, at all the concentrations tested. In addition, phycocyanin-loaded vesicles protected the cells against free radical damage. In vivo studies were performed to evaluate the ability of santosomes to inhibit chemically-induced oedema and inflammation in mice. Results demonstrated that the application of phycocyanin-loaded santosomes produced an evident amelioration of the skin lesion, confirming their great potential for wound healing., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In this work, we focused on how composition and preparation method of vesicles might affect their morphological features and delivery performances. Penetration Enhancer-containing Vesicles, PEVs, vesicles containing a water miscible penetration enhancer (Transcutol® P; 10%, 20%, 30% v/v) and encapsulating diclofenac sodium, were formulated and compared with conventional liposomes. A cheap and unpurified commercial mixture of phospholipids, fatty acids, and triglycerides (Phospholipon® 50) was used, and the effects of this heterogeneous composition (along with the presence or absence of transcutol and the production method) on vesicle morphology, size, surface charge, drug loading, and stability were investigated. The variations in vesicle structure, bilayer thickness, and number of lamellae were assessed by TEM and Small and Wide Angle X-ray Scattering, which also proved the liquid state of the vesicular bilayer. Further, vesicles were evaluated for ex vivo (trans)dermal delivery, and their mode of action was studied performing a pre-treatment test and confocal laser scanning microscopy analyses. Results showed the formation of multi- and unilamellar vesicles that provided improved diclofenac delivery to pig skin, influenced by vesicle lipid composition and structure. Images of the qualitative CLSM analyses support the conclusion that PEVs enhance drug transport by penetrating intact the stratum corneum, thanks to a synergic effect of vesicles and penetration enhancer., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recently, we described a novel family of liposomes, the Penetration Enhancer-containing Vesicles (PEVs), as carriers for enhanced (trans)dermal drug delivery. In this study, to go deeply into the potential of these new vesicles and suggest the possible mechanism of vesicle-skin interaction, we investigated transcutol containing PEVs as carriers for diclofenac, in the form of either acid or sodium salt. PEVs, prepared with soy phosphatidylcholine and aqueous solutions containing different concentrations of transcutol, were characterized by size distribution, zeta potential, incorporation efficiency, thermotropic behavior, and stability. (Trans)dermal diclofenac delivery from PEVs was investigated ex vivo through new born pig skin using conventional liposomes and a commercial gel as controls. The mode of action of the vesicles was also studied by performing a pre-treatment test and confocal laser scanning microscopy (CLSM) analyses. Results of the all skin permeation experiments showed an improved diclofenac (both acid and sodium salt) delivery to and through the skin when PEVs were used (especially in comparison with the commercial gel) thus suggesting intact PEVs' penetration through the pig skin. Images of the qualitative CLSM analyses support this conclusion. Thus, this work shows the superior ability of the PEVs to enhance ex vivo drug transport of both hydrophilic and lipophilic diclofenac forms., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Resveratrol (RSV) has proven potential in prophylaxis and treatment of various disorders mediated by free radicals and oxidative stress. RSV solubility, stability, and cytotoxicity must be regulated for satisfactory bioavailability. Here, RSV was loaded into liposomes, characterized by PCS and TEM and evaluated on HEK293 cell line by metabolic activity assay, electron paramagnetic resonance, and fluorescence microscopy. RSV at 10 microM induced changes in cell metabolic activity and significantly improved antioxidative capacity. At 100 microM it showed concentration-dependent cytotoxicity. Oligolamellar liposomes with mean diameter 84 nm, polydispersity index 0.2, and zeta potential -40 mV showed high entrapment of RSV and rapid cellular internalization. Cell stress caused by UV-B irradiation diminished cell metabolic activity by 50%. RSV loaded into them showed no cytotoxicity at 100 microM and stimulated cellular metabolic and antioxidant activity levels to eliminate the harmful effect of the stress. Localization of RSV within liposomal bilayer is crucial for stimulation of cell-defense system, prevention of RSV cytotoxicity, and its long-term stability. In summary, evidence of different metabolic activity using free RSV and LIP-RSV is presented indicating that liposome-mediated uptake of RSV is more effective for improvement of the cell-stress response.