Publications

Scalability is one of the important factors slowing down or even impeding the clinical translation of nanoparticle-based systems. The latter need to be manufactured at a high level of quality, with batch-to-batch reproducibility, and need to be stable after the manufacturing process, during long-term storage and upon clinical administration. In this study, a vesicular formulation intended for cutaneous applications was developed by the easy reconstitution of a commercially available liposomal platform. Resveratrol, a naturally occurring compound with potent antioxidant activity, and Tween80, a hydrophilic non-ionic surfactant, were included in the formulation. The physico-chemical properties of the vesicles were assessed using light scattering and cryogenic transmission electron microscopy. Nanosized (around 80 nm) spherical and elongated, unilamellar vesicles were produced, with remarkable storage stability. The incorporation of resveratrol in the vesicular system did not alter its strong antioxidant activity, as demonstrated by antioxidant colorimetric assays (DPPH and FRAP). Furthermore, the resveratrol liposomes were cytocompatible with fibroblasts and capable of protecting skin cells from oxidative stress by reducing both endogenous and chemically induced reactive oxygen species more effectively than free resveratrol. Therefore, the proposed formulation, based on the use of a commercially available liposomal platform, represents an easy-to-prepare, reproducible, up-scaled and efficient means of delivering resveratrol and potentiating its biological activity in vitro.

JTD Keywords: antioxidant, commercial liposomes, resveratrol, skin cells, skin delivery, Antioxidant, Commercial liposomes, Drug-delivery, Resveratrol, Skin cells, Skin delivery

© 2020 Elsevier B.V. Resveratrol and artemisinin, two naturally occurring compounds with a wide range of biological activities, have been reported to exert antitumor effects against several types of cancer. In this work, Eudragit-coated liposomes were developed to safely transport resveratrol and artemisinin through the gastrointestinal tract and target the intestine. The physico-chemical properties of the Eudragit-coated liposomes were assessed by light scattering and cryogenic transmission electron microscopy. Nanosized (around 100 nm), spherical or elongated, unilamellar vesicles were produced. The protective effect of the Eudragit coating was confirmed by assessing the physical stability of the vesicles in fluids mimicking the gastrointestinal environment. Furthermore, the vesicles were found to exert a pro-oxidant activity in intestinal adenocarcinoma cells, which resulted in a marked mortality due to the generation of reactive oxygen species (ROS). A time- and dose-dependent cell growth inhibitory effect was detected, with elevated ROS levels when resveratrol and artemisinin were combined. Therefore, the proposed formulations may represent a valuable means to counteract intestinal tumor growth.

JTD Keywords: antitumor, artemisinin, eudragit, intestinal delivery, liposomes, Antitumor, Artemisinin, Eudragit, Intestinal delivery, Liposomes, Resveratrol

The present investigation reports the development of PEG-modified liposomes for the delivery of naturally occurring resveratrol. PEG-modified liposomes were prepared by direct sonication of the phospholipid aqueous dispersion, in the presence of two PEG-surfactants. Small, spherical, unilamellar vesicles were produced, as demonstrated by light scattering, cryo-TEM, and SAXS. The aging of the vesicles was assessed by using the Turbiscan® technology, and their physical stability was evaluated in vitro in simulated body fluids, results showing that the key features of the liposomes were preserved. The biocompatibility of the formulations was demonstrated in an ex vivo model of hemolysis in human erythrocytes. Further, the incorporation of resveratrol in PEG-modified liposomes did not affect its intrinsic antioxidant activity, as DPPH radical was almost completely inhibited, and the vesicles were also able to ensure an optimal protection against oxidative stress in an ex vivo human erythrocytes-based model. Therefore, the proposed PEG-modified liposomes, which were prepared by a simple and reliable method, represent an interesting approach to safely deliver resveratrol, ensuring the preservation of the carrier structural integrity in the biological fluids, and the antioxidant efficacy of the polyphenol to be exploited against oxidative stress associated with cancer.

JTD Keywords: Resveratrol, Antioxidant, PEG-surfactants, PEG-modified liposomes, Human erythrocytes

In the present work, quercetin and resveratrol, natural polyphenols with strong antioxidant and anti-inflammatory properties, were co-loaded in polymer-associated liposomes conceived for oral delivery, by exploiting the potential of pH-sensitive succinyl-chitosan. Chitosan was succinylated, characterized by Nuclear Magnetic Resonance spectroscopy and Gel Permeation Chromatography, and used to form a protective shell on the surface of liposomes. The physico-chemical properties of the succinyl-chitosan liposomes were assessed by light scattering, zeta potential, cryogenic transmission electron microscopy, and small angle X-ray scattering. Small, spherical, uni- and bilamellar vesicles were produced. The succinyl-chitosan shell increased not only the physical stability of the vesicular system, as demonstrated by accelerated stability tests, but also the release of the polyphenols to a greater extent at pH 7.0, mimicking the intestinal environment. The proposed approach based on polyphenol vesicular formulations may be of value in the treatment of pre-cancerous/cancerous intestinal conditions associated with inflammation and oxidative stress.

JTD Keywords: Antioxidant, Liposome, Oral delivery, Quercetin, Resveratrol, Succinyl-chitosan

The present investigation reports the development of liposomes for the co-delivery of naturally occurring polyphenols, namely quercetin and resveratrol. Small, spherical, uni/bilamellar vesicles were produced, as demonstrated by light scattering, cryo-TEM, SAXS. The incorporation of quercetin and resveratrol in liposomes did not affect their intrinsic antioxidant activity, as DPPH radical was almost completely inhibited. The cellular uptake of the polyphenols was higher when they were formulated in liposomes, and especially when co-loaded rather than as single agents, which resulted in a superior ability to scavenge ROS in fibroblasts. The in vivo efficacy of the polyphenols in liposomes was assessed in a mouse model of skin lesion. The topical administration of liposomes led to a remarkable amelioration of the tissue damage, with a significant reduction of oedema and leukocyte infiltration. Therefore, the proposed approach based on polyphenol vesicular formulation may be of value in the treatment of inflammation/oxidative stress associated with pre-cancerous/cancerous skin lesions.

JTD Keywords: Antioxidant, Fibroblast, Liposome, Quercetin, Resveratrol, Skin lesion