479. PARTICLE SIZE AND BILAYER RIGIDITY EFFECTS ON SKIN DIFFUSION OF NANOSOMES.

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Papazoglou^1,2, E.S., Babu¹, S., Fan¹, C., Sunkari¹, C., and Uitto², J. ¹Biomedical Engineering, Drexel University, Philadelphia, PA and ²Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA. Abstract International Invest. Dermatol., Abstract 324, May (2008).

Summary:
This study by researchers at Drexel University and Thomas Jefferson University demonstrated that MatTek's EpiDerm in vitro human skin tissue equivalent can be used to mimic human skin's diffusion characteristics for nano-sized particles.

Diffusion of micron size liposomes through skin depends on their size, the lipid bilayer deformability and their charge.

In this study, researchers at Drexel University and Thomas Jefferson University report the effect of liposome size at the nanoscale and deformability on diffusion of neutral charge liposomes through MatTek (human) skin equivalents.

Liposomes were prepared by the reverse phase evaporation method followed by extrusion through polycarbonate membranes of various pore sizes. Particle size was determined by particle size analysis and revealed a narrow distribution around the mean. The deformability of these liposomes was determined by selecting the phase transition temperature of the constituent lipids. DPPC [1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine, phase transition temperature: 40C] and DOPC [1,2-Dioleoyl-sn-Glycero-3-Phosphocholine, phase transition temperature: -20C] mixed with fluorescent lipid with NBD [1-Oleoyl-2-[12-[(7-nitro-2-l,3-benzoxadiazol-4-yl) amino]dodecanoyl]
-sn-Glycero-3-Phosphocholine] in 1000:1 mole ratio were used to prepare the liposomes used in this study.

Diffusion experiments were carried out at 37C in a Franz diffusion cell. Concentration of liposomes in the receptor compartment at various time points was determined by measuring the fluorescence intensity from the solution in the receptor compartment.

Our results indicate that the diffusion of particles between 50 and 70 nm is independent of the rigidity of the lipid bilayer, while diffusion of particles larger than 100 nm is mainly dictated by the lipid bi-layer rigidity.

These results could have a significant impact on selection of liposomes for transdermal delivery and on the impact of skin exposure to nanoparticles.

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Applications: Drug absorption - skin, Drug delivery - transdermal, Nanotechnology, Percutaneous absorption/penetration, Transdermal permeation/penetration

Keywords: Diffusion, EPI-606X, EpiDerm, Franz diffusion cell, Liposomes, Nanomaterials, Nanoparticles, Nanosomes, Nanotechnology

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