Oleuropein multicompartment nanovesicles enriched with collagen as a natural strategy for the treatment of skin wounds connected with oxidative stress.

Aim: Collagen-enriched transfersomes, glycerosomes and glytransfersomes were specifically tailored for skin delivery of oleuropein. Methods: Vesicles were prepared by direct sonication and their main physicochemical and technological properties were measured. Biocompatibility, protective effect and promotion of the healing of a wounded cell monolayer were tested in vitro using fibroblasts. Results: Vesicles were mainly multicompartment, small (∼108 nm), slightly polydispersed (approximately 0.27) and negatively charged (~-49 mV). Oleuropein was incorporated in high amounts (approximately 87%) and vesicles were stable during four months of storage. In vitro studies confirmed the low toxicity of formulations (viability ≥95%), their effectiveness in counteracting nitric oxide generation and damages caused by free oxygen radicals, especially when collagen glytransfersomes were used (viability ~100%). These vesicles also promoted the regeneration of a wounded area by promoting the proliferation and migration of fibroblasts. Conclusion: Collagen-enriched vesicles are promising formulations capable of speeding up the healing of the wounded skin.

Glycerosomes: Use of hydrogenated soy phosphatidylcholine mixture and its effect on vesicle features and diclofenac skin penetration.

In this work, diclofenac was encapsulated, as sodium salt, in glycerosomes containing 10, 20 or 30% of glycerol in the water phase with the aim to ameliorate its topical efficacy. Taking into account previous findings, glycerosome formulation was modified, in terms of economic suitability, using a cheap and commercially available mixture of hydrogenated soy phosphatidylcholine (P90H). P90H glycerosomes were spherical and multilamellar; photon correlation spectroscopy showed that obtained vesicles were ∼131nm, slightly larger and more polydispersed than those made with dipalmitoylphosphatidylcholine (DPPC) but, surprisingly, they were able to ameliorate the local delivery of diclofenac, which was improved with respect to previous findings, in particular using glycerosomes containing high amount of glycerol (20 and 30%). Finally, this drug delivery system showed a high in vitro biocompatibility toward human keratinocytes.

Fabrication of polyelectrolyte multilayered vesicles as inhalable dry powder for lung administration of rifampicin.

A polyelectrolyte complex based on chitosan and carrageenan was used to coat rifampicin-loaded vesicles and obtain a dry powder for inhalation by spray-drying. The polymer complexation on vesicle surface stabilized them and improved their adhesion on airways and epithelia cells. Uncoated liposomes were small in size, negatively charged and able to incorporate large amounts of rifampicin (70%). Coated vesicles were still able to load adequate amounts of drug (∼70%) but the coating process produced larger particles (1 µm) that were positively charged and with a spherical shape. Aerosol performances, evaluated using the next-generation impactor, showed that coated vesicles reached the 50% of fine particle fraction and the smallest mass median aerodynamic diameter (2 µm). Rifampicin-loaded uncoated and coated vesicles slowly reduced the A549 cell viability over a 48-h incubation time. Moreover, in vitro coated formulations had a strong ability to be easily internalized and to greatly prolong the residence time of their components in A549 cells compared to uncoated liposomes that were rapidly internalized and just as quickly removed.

Inhibition of skin inflammation in mice by diclofenac in vesicular carriers: liposomes, ethosomes and PEVs.

Diclofenac-loaded phospholipid vesicles, namely conventional liposomes, ethosomes and PEVs (penetration enhancer-containing vesicles) were developed and their efficacy in TPA (phorbol ester) induced skin inflammation was examined. Vesicles were made from a cheap and unpurified mixture of phospholipids and diclofenac sodium; Transcutol P and propylene glycol were added to obtain PEVs, and ethanol to produce ethosomes. The structure and lamellar organization of the vesicle bilayer were investigated by transmission electron microscopy and small and wide angle X-ray scattering, as well as the main physico-chemical features. The formulations, along with a diclofenac solution and commercial Voltaren Emulgel, were tested in a comparative trial for anti-inflammatory efficacy on TPA-treated mice dorsal skin. Vesicles were around 100 nm, negatively charged, able to encapsulate diclofenac in good yields, and disclosed different lamellarity, as a function of the formulation composition. Vesicular formulations promoted drug accumulation and reduced the permeation. Administration of vesicular diclofenac on TPA-inflamed skin resulted in marked attenuation of oedema and leucocyte infiltration, especially using PEVs. Histology confirmed the effectiveness of vesicles, since they provided an amelioration of the tissual damage induced by TPA. The proposed approach based on vesicular nanocarriers may hold promising therapeutic value for treating a variety of inflammatory skin disorders.