Topical drug delivery has been studied by scientists for several decades. However, research regarding the role and importance of the hair follicle in drug permeation is still inconclusive. It is thought by many that targeted delivery to the hair follicle by properly designed topical formulations could lead to superior treatments for conditions associated with the pilosebaceous unit including acne, alopecia (hair loss) and body odor. In particular, liposomes and polymeric microparticles have been investigated for this purpose. The aims of the present project were two-fold: (1) to develop methods for eventual incorporation into anti-perspirant/deodorant products; and (2) to investigate a recently reported in vitro permeation model involving selective blocking of follicles as a tool for studying follicular delivery.
To progress Aim 1, cetylpyridinium chloride (CPC) and hexylresorcinol (HR) were incorporated into nonionic liposome formulations and cellulose acetate butyrate microparticles by a variety of methods. Stability and encapsulation efficiency were studied by a combination of optical microscopy, static light scattering, dynamic light scattering, filtration and equilibrium dialysis followed by UV-visible spectrophotometry. An anionic surfactant, N-myristoyl sarcosine Hamposyl-M™ was added to some of the CPC formulations in an attempt to make a lipophilic ion pair that would better incorporate into the particulate phase. Hexanediol was added to some of the HR formulations to improve the solubility of this very lipophilic agent. None of the formulations prepared effectively encapsulated either CPC or HR. We found that nonionic liposomes prepared by standard methods were polydisperse and showed evidence of a significant micellar component in addition to liposomes. The polymeric microparticles formed properly, but failed to encapsulate the antimicrobial agents. Consequently, neither the liposomal or microparticle formulations were tested on skin.
Aim 2 involved testing an in vitro model for follicular delivery in which the follicles in excised pig ear skin were selectively blocked by dotting them with a cyanoacrylate adhesive. Following mounting in Franz cells, the permeation of radiolabeled Mannitol was studied. Three treatments were tested- untreated skin, follicle-blocked skin and skin in which an equivalent amount of adhesive was applied to interfollicular sites- under two conditions, occluded skin and unoccluded skin. Both conditions yielded similar patterns for Mannitol skin permeation: untreated ≫ follicle-blocked ≥ interfollicular-treated. Thus, there was no evidence for Mannitol permeation through hair follicles. We concluded that the glue spread on the skin after application and blocked mannitol permeation over a substantial fraction of the skins surface. Further refinement of the test conditions is required to make this a useful model for follicular delivery.