Liposomes for (trans)dermal drug delivery: the skin-PVPA as a novelin vitro stratum corneummodel in formulation development

Abstract

Penetration potential of vesicles destined for trans(dermal) administration remains to be of great interests both in respect to drug therapy and cosmetic treatment. This study investigated the applicability of the phospholipid vesicle-based permeation assay (PVPA) as a novel in vitro skin barrier model for screening purposes in preformulation studies. Various classes of liposomes containing hydrophilic model drug were examined, including conventional liposomes (CLs), deformable liposomes (DLs) and propylene glycol liposomes (PGLs). The size, surface charge, membrane deformability and entrapment efficiency were found to be affected by the vesicle lipid concentration, the presence of the surfactant and propylene glycol. All liposomes exhibited prolonged drug release profiles with an initial burst effect followed by a slower release phase. The permeation of the drug from all of the tested liposomes, as assessed with the mimicked stratum corneum--PVPA model, was significantly enhanced as compared to the permeability of the drug in solution form. Although the DLs and the PGLs exhibited almost the same membrane elasticity, the permeability of the drug delivered by PGLs was higher (6.2 × 10⁻⁶ cm/s) than DLs (5.5 × 10⁻⁶ cm/s). Therefore, this study confirmed both the potential of liposomes as vesicles in trans(dermal) delivery and potential of the newly developed skin-PVPA for the screening and optimization of liposomes at the early preformulation stage.

Elastic liposomes-in-vehicle formulations destined for skin therapy: the synergy between type of liposomes and vehicle

“…The results (Table 2) cases; the drug release from propylene glycol liposomes and especially deformable vesicles was significantly faster (p < 0.05). These results were in agreement with the previous study 19 ,…”

“…This result may be explained by the ability of propylene glycol to solubilize phospholipids and intercalate into the bilayer 13,31,32 , affecting the membrane flexibility of the vesicles. Regarding the surface charge, all of the liposomes had highly negative zeta potentials (> -50 mV), indicating the formation of physically stable liposome suspensions, which was confirmed in the storage stability studies 19 .…”

“…Membrane elasticity of extruded liposomes was evaluated by home-made device at an external pressure of 5 bar using 100-nm membranes. Detailed procedure with equation for calculation of the deformability degree (E) has been previously described in details 14,19 . Separation of the unentrapped drug was performed using gel chromatography on Sepharose CL-4B 22 .…”

“…Separation of the unentrapped drug was performed using gel chromatography on Sepharose CL-4B 22 . Thereafter, the liposomal fraction was concentrated using ultracentrifugation as previously described 19 . The concentrations of both the unentrapped (free) and liposome-entrapped drug were determined spectrophotometrically (Ultrospect Plus, Pharmacia LKB, Cambridge, UK).…”

“…Deformable, propylene glycol and conventional liposomes were prepared by the film hydration method, followed by extrusion, as previously described 19 . Briefly, lipid components were dissolved in concentrated ethanol in a round bottomed flask.…”