Ex vivo skin delivery of diclofenac by transcutol containing liposomes and suggested mechanism of vesicle–skin interaction

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 78; no. 1; pp. 27 - 35
• Main Authors: Manconi, Maria, Caddeo, Carla, Sinico, Chiara, Valenti, Donatella, Mostallino, Maria Cristina, Biggio, Giovanni, Fadda, Anna Maria
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-05-2011; Elsevier
• Subjects: (Trans)dermal delivery; Animals; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage; Biological and medical sciences; Confocal laser scanning microscopy; Diclofenac - administration & dosage; General pharmacology; Liposome; Liposomes; Medical sciences; Microscopy, Confocal; Microscopy, Electron; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rheology; Skin - metabolism; Swine; Transcutol; Vesicle–skin interaction; Liposome; Vesicle–skin interaction; Rheology; (Trans)dermal delivery; Transcutol; Confocal laser scanning microscopy; Vesicle; Prostaglandin-endoperoxide synthase; Pharmaceutical technology; Enzyme; Interaction; Enzyme inhibitor; Confocal microscopy; Vesicle-skin interaction; Diclofenac; Percutaneous route; Non steroidal antiinflammatory agent; Arylacetic acid derivatives; Analgesic; Ex vivo; Antipyretic; Microparticle; Skin; Oxidoreductases; Mechanism of action; Rheology (Trans)dermal delivery
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.12.010

Novel transcutol containing PEVs showed to be suitable carriers for dermal delivery of diclofenac. Confocal Laser Scanning Microscopy was also used to visualize vesicle-skin interactions.
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.