a large surface area for potential absorption of compounds, because of an enfolding of the epidermis extending deeply into the dermis.19 Characteristics for entry into the hair follicle unit include low molecular weight, generally not more than 600 Da. In addition entry to sWAT via the hair follicle can be further facilitated by the use of specifically designed liposomes which provide an ideal carrier for the topical agent.19 It has been suggested that the size of a particle determines the depth of follicular penetration.20 Topically applied liposomal encircled peptides tend to diffuse and accumulate in the hair follicle, this deposit acting as a reservoir for ongoing functional activities. Particles of ~300 nm in size penetrate more deeply into the pilosebaceous unit than non-particle contents.19 Additionally, particles less than 200nm have demonstrated superiority over nonparticle formulations in terms of storage behavior.21 Thus, a targeted approach of liposome (lipoDRONETM) surrounded Hex-11 has been designed to deliver quick and efficient loads of peptide to the base of the hair follicle where it provides an ongoing reservoir for delivery to surrounding dWAT which then directly communicates with sWAT producing the desired autophagic responses (Figure 3). Unifying Hypothesis of Topical Modulation of Adipose Tissue
Non-surgical fat reduction and body sculpting are currently extremely popular procedures. The common end result of the technologies described above is slow dissolution of the products of adipose cell breakdown. Macrophage digestion and excretion of these end products is dependent on adequate break down of these droplets into sized packages suited to macrophage efficiency. As described above, an important process in achieving this end is autophagy (or lipophagy), which involves repackaging of the large droplets into manageable sizes. Although not commonly recognized, peptides exist with specific amino acid sequences that have a profoundly positive effect on the autophagic process. One such peptide, a hexapeptide, was selected to investigate its potential in dealing with lipid droplet byproducts. The peptidewas first subjected to gene expression tests (Predictive Bio, Carlsbad, CA) to assess responses appropriate to autophagic functions. Primary dermal fibroblasts were plated in cell culture media and allowed to grow to 90% confluency. Cells were then harvested and plated at 10,000 cells per cm2 in 6-well dishes and cultured for 3 days. On day 3, the peptide was added to the
