Penetration-enhancing activity

FIGURE 12.1 Penetration enhancer activity, (a) Action at intercellular lipids. Some of the ways by which penetration enhancers attack and modify the well-organized intercellular lipid domain of the stratum comeum. (b) Action at desmosomes and protein structures. Such dramatic disruption by enhancers (particularly potent solvents) as they split the stratum corneum into additional squames and individual cells would be clinically unacceptable, (c) Action within comeocytes. Swelling, further keratin denaturation and vacuolation within individual horny layer cells would not be so drastic but would usually be cosmetically challenging (see Menon and Lee [69] for further details). (Reproduced from Barry, B.W., Nat. Biotechnol. 22, 165, 2004. With permission.)... 

Urea is a hydrating agent (a hydrotrope) used to treat scaling conditions such as psoriasis, ichthyosis, and other hyperkeratotic skin conditions. Applied in a water-in-oil vehicle, urea alone or in combination with ammonium lactate hydrated stratum corneum and improved barrier function when compared to the vehicle alone in human volunteers in vivo [45], Urea also has keratolytic properties, usually when combined with salicylic acid for keratolysis. The somewhat modest penetration-enhancing activity of urea probably arises from a combination of increasing stratum corneum water content (water is a valuable penetration enhancer) and through the keratolytic activity. 

It is of course not only the concentration of water that may be deduced by this methodology in fact, any penetrant possessing a characteristic IR signature, distinct from the SC components, can be similarly monitored. Consequently, one of the noteworthy uses of reflectance spectroscopy has been the in vivo evaluation of penetration enhancement, both in the assessment of enhancer efficacy and in the investigation of their mode of action. The basis of this research, however, lies in the extensive in vitro investigations, by IR and DSC, of penetration enhancer activity and it is therefore pertinent to first review the principal literature. 

Michniak, B.B. Player, M.R. Sowell, J.W. S3mthesis and in vitro transdermal penetration enhancing activity of lactam N-acetic acid esters, J.Pharm.Sci., 1996, 85, 150-154... 

The penetration-enhancing activities of monoterpenes, sesquiterpenes, and diter-penes were evaluated. Terpenes with relatively high lipophilic index exhibited absorption-promoting effects however, extremely high Upophilicity led to lower enhancing activities (Takayama et al., 1991). It was suggested that the difference in percutaneous absorption enhancing efficiency of terpenes arose from the difference in their thermodynamic activities in the vehicle (Obata et al., 1993). 

This chapter deals with an overview of the research results of antibacterial, antiviral, antinocicep tive, anti-in ammatory, vasodilatory, and penetration enhancing activity of essential oils (EO) and covers the literature from 2009 to March 2014. It is well known that EOs exert many effects in the human and animal body. Many authors before have described several biological activities. This treatise should afford an overview of the research results concerning the aforementioned topics from 2009 to 2014 following earlier chapters. The treatment of common disease and indispositions, rheumatoid arthritis, pain, high blood pressure, cancer, and many more, with alternative methods such as EOs, is still current. Because of a high rate of resistances against common treatment, science is in the quest of alternative or at least complementary treatment opportunities. 

Yuan et al. (2014) found that the EO of Asarum mialaicum Hook.f. and Thomson ex Klotzsch (Aristolochiaceae) has penetration-enhancing activities. Patches impregnated with 15%-35% EO increased penetration by 10%-20%. 

The volatile oils of Flos caryophylli, Semen myristicae, and Fructus anisi stellati were found to exhibit penetration-enhancing activities on ligustrazine phosphate. EOs at 3%, 5%, and 7% were compared to 3% of azone, a prominent permeation enhancer. The EO of F. caryophylli showed the highest enhancing effect (Luo et al., 2013). 

Black cumin seed oil Nigella sativa L., Ranunculaceae) was tested for its penetration enhancer activity on carvedilol using excised albino Wistar rat abdominal skin. At a concentration of 5% the EO showed the most potent enhancing effects. The transdermal ux and the permeability coef -dent were higher than in the control group (Saima et al., 2010). 

When diabetic rabbits (24) were treated with 50 IU of bovine insulin imbibed at 50 mg/g poly (acrylic acid) (Figure 14) no reduction in serum glucose over that achieved by the dry blend control could be detected. Pretreatment of the animals with oral doses of either a penetration enhancer, sodium taurocholate, or a protease inhibitor, aproteinin, failed to improve the insulin activity. One possible explanation for this unexpected lack of activity might be that the diseased animals exhibit impaired ileal absorption of fluids (25). 

The permeability of the colonic epithelimn may not be suffieient for aehieving a transport rate required for therapeutic activity. This hurdle may be overeome, at least in part, by using the penetration enhancers listed below [36]. 

The lack of significant impact of CPEs on transdermal delivery vehicles is related to the inherent nonspecific activity of CPEs in the different strata of the skin, as discussed earlier. This limitation may be overcome by utilization of mixtures of CPEs. Research has already shown that binary mixtures of CPEs provide increased permeation enhancement as well as increased safety compared to single enhancers. Such unique chemical combinations, called synergistic combinations of penetration enhancers or SCOPE formulations, offer new opportunities in transdermal drug delivery (46). 

Figure 2 (A) Design of a ternary formulation. (B) Activity phase map of a ternary combination of chemical penetration enhancers. Dark gray indicates highest skin permeabilization and light gray indicates lowest skin permeabilization.

Kanikkannan N, Kandimalla K, Lamba S, Singh M. Structure-activity relationship of chemical penetration enhancers in transdermal drug delivery. Curr Med Chem 2000 7 593-608. 

A wide variety of long-chain fatty acids increase transdermal delivery the most popular is oleic acid. It is relevant that many penetration enhancers contain saturated or unsaturated hydrocarbon chains and some structure-activity relationships have been drawn from the extensive studies of Aungst et al. [22,23] who employed a range of fatty acids and alcohols, sulfoxides, surfactants, and amides as enhancers for naloxone. From these experiments, it appears that saturated alkyl chain lengths of around Cio to C12 attached to a polar head... 

Some glycosides with surface activity have been used successfully as penetration enhancers. 

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