Alpar, HO

Dahlan, A

Murdan, S

UCL Discovery

Effect of surfactant concentration on sonophoresis of proteins throughrat skinA. Dahlan, H. O. Alpar and S. MurdanDepartment of Pharmaceutics, School of Pharmacy, University of London, 29-39Brunswick Square, London WC1N 1AX, UK. Email: afendi.dahlan@ulsop.ac.ukThe synergistic effect of sodium lauryl sulphate (SLS) normally at 1% and lowfrequencyultrasound (US) in transdermal drug delivery has been established(Mitragotri et al 2000). However, due to the potential skin irritancy of SLS, theuse of 1% surfactant concurrently with US could be pharmaceutically unacceptable.The aim of this study was to explore the relationship between surfactantconcentration and enhancement of transdermal protein delivery by low-frequencyultrasound. Permeation studies using Franz cells were conducted using full-thicknessrat skin as the membrane, and the receptor phase (4mL) was phosphatebuffered saline (PBS). The donor compartment was filled with 20mL of couplingmedium (water or SLS aqueous solution at different concentrations: 0.001, 0.004,0.01, 0.04, 0.1 and 1%) and ultrasound (30% amplitude, 0.5 s on, 0.5 s off pulsewave for a total sonication time of 2min) was applied with the transducer being5mm from the skin surface. Following ultrasound application, the couplingmedium was removed from the donor compartment and the skin was rinsed andblotted dry, and 50 _L of iodine-125 labelled bovine serum albumin (BSA) wasapplied onto the skin. After 24 h, the levels of radioactivity in the receptor compartment (e.g., 0.1%), protein permeation into skin wasincreased despite the lack of pitsformed on aluminium foil. This indicates that protein was permeating through theskin via pathways that could not be related to pits formed on aluminium foil. Thisstudy has shown that very low concentrations of SLS (e.g., 0.001%) resulted insimilar protein permeation to those achieved by 1% SLS. The lower SLS concentrationhas advantages, such as lower toxicity.Mitragotri, S. et al (2000) J. Pharm.Sci. 89: 892–900and in the skin were measured using a gamma counter. Gel electrophoresison the receptor phase confirmed BSA presence. It was found that when0.001% and 0.004% SLS solutions were used as the coupling medium, proteinpermeation into the receptor phase was similar to those obtained when water wasused as couplingmedium. Surprisingly, an increase in SLS concentration to 0.01%and 0.04% resulted in a marked decrease in protein permeation. A further increasein SLS concentration to 0.1% to 1% resulted in increased protein. To understandthe protein permeation profile at the different surfactant concentrations, the surfacetension of the different SLS solutions were measured and aluminium foilpitting experiments were conducted. The latter are conducted by applying ultrasoundwaves to an aluminium foil using different SLS solutions as couplingmedium and counting the number of pits formed on the aluminium foil. Thenumber of pits gives an indication of the damage caused to skin by ultrasound.There seems to be some correlation between surface tension of SLS solutions andnumber of pits formed and protein permeation at low SLS concentrations.Increasing surfactant concentration from 0 to 0.04% led to decreased surfacetension, decreased number of pits and decreased protein through the skin. Thereduced damage caused to skin (equivalent to fewer pits on aluminium foil)may beresponsible for the decreased protein permeation. At higher SLS concentrations

Abstract: Effect of surfactant concentration on sonophoresis of proteins through rat skin

http://discovery.ucl.ac.uk/1351440/1/Effect_of_surfactant_concentration_on_sonophoresis_of_proteins_through.pdf

Abstract: Effect of surfactant concentration on sonophoresis of proteins through rat skin

Abstract

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