Cutaneous delivery

Cutaneous and Transdermal Delivery—Processes and Systems of Delivery... 

While the model helps us understand the chemical structure dependencies of skin permeability, it isn t all that useful for calculating permeability coefficients because of the many iffy assumptions it contains. A different tack has to be taken to gain a sense of the limits, especially the upper limit, of cutaneous drug delivery. There is no lower limit. Even proteins penetrate intact skin to some extent. Some idea of the upper... 

M. Kreilgaard. Assessment of cutaneous drug delivery using microdialysis. Adv. Drug Deliv. Rev. 54 S99-S I2 I (2002). 

F.-X. Mathy, C. Lombry, R. Verbeeck, and V. Preat. Study of percutaneous penetration of flubiprofen by cutaneous and subcutaneous microdialysis after iontophoretic delivery in rat. J. Pharm. Sci. 94 144—152 (2005). 

Since the use of human plasma as a model for skin esterases is debatable, the relevance of the biological results in Table 8.6 need validation as far as skin delivery is concerned. Indeed, permeation experiments across excised human skin showed that administration of prodrugs markedly improved the cutaneous delivery of nalidixic acid, with complete hydrolysis of the (acyl-oxy)methyl esters and significant, albeit incomplete, hydrolysis of the methyl and carbamoylmethyl esters [64],... 

Kreilgaard M. Influence of microemulsions on cutaneous drug delivery. Adv Drug Delivery Rev 2002 54 S77-S98. 

Fresta, M., and G. Puglisi. 1996. Application of liposomes as potential cutaneous drug delivery systems. In vitro and in vivo investigation with radioactively labelled vesicles. J Drug Target 4 95. 

Babiuk, S., et al. 2000. Cutaneous vaccination The skin as an immunologically active tissue and the challenge of antigen delivery. J Control Release 66 199. 

Whereas microneedles are designed to pierce through the outer layers of skin, the controlled destruction or adhesive removal of the stratum corneum represent alternative methods for overcoming the penetrative barrier to cutaneous drug delivery. 

Chabri, F., et al. 2004. Microfabricated silicon microneedles for nonviral cutaneous gene delivery. 

Larregina, A.T. and L.D. Falo. 2000. Generating and regulating immune responses through cutaneous gene delivery. Hum Gene Ther 11 2301. 

Cutaneous biotransformation is mostly associated with the stratum basale layer where there can be phase I and phase II metabolism. However, the skin is not very efficient, compared to the liver. The epidermal layer accounts for the major portion of biochemical transformations in skin, although the total skin activity is low (2-6% that of the liver). Where activity is based on epidermis alone, that layer is as active as the liver or, in the case of certain toxicants, several times more active. For some chemicals, metabolism can influence absorption, and transdermal delivery systems of drugs utilize this activity. For example prodrug such as lipid esters are applied topically, and cutaneous esterases liberate the free drug. These basal cells and extracellular esterases have been shown to be involved in detoxification of several pesticides and bioactivation of carcinogens such as benzo(a)pyrene. For rapidly penetrating substances, metabolism by the skin is not presently considered to be of major significance, but skin may have an important first-pass metabolic function, especially for compounds that are absorbed slowly. 

P. Wotton, B. Mollgaard, J. Hadgraft, and A. Hoelgaard, Vehicle effect on topical drug delivery. III. Effect of azon on the cutaneous permeation of metronidazole and propylene glycol, Int. J. Pharm. 24 19-26 (1985). 

The different steps involved in drug transfer from a delivery system to the cutaneous circulation are shown in Figure 2 [7-10]. Drugs diffusing through the skin may be subject to various loss processes which are difficult to quantify but will be discussed. The first step in the total transfer process is diffusion from the device. In its simplest form, the device could be an ointment base which will... 

Figures (5) and (6) show respectively the predicted profiles for propranolol and chlordiazepoxide. It is immediately apparent that propranolol is a drug candidate which could be considered for delivery using this route of administration. The delivery of chlordiazepoxide is, however, unlikely to succeed. The primary reason for this is the large value of kg such that drug transfer out of the stratum corneum is slow. Thus drugs which are very lipophilic in nature can partition well into the stratum corneum but transfer out of this region impedes the arrival of the drug at the cutaneous vasculature. The only method of circumventing this...

Weiner, N., Williams, N., Birch, G., Ramachandran, R., Shipman, C., Jr., and Flynn, G. (1989),Topical delivery of liposomally encapsulated interferon evaluated in a cutaneous herpes guinea pig model, Antimicrob. Agents Chemoter., 33,1217-1221. 

Noonan, P.K. and R.C. Wester (1989). Cutaneous metabolism of xenobiotics, in Percutaneous Absorption Mechanisms, Methodology, Drug Delivery, 2nd Edn, R.L. Bronaugh and H.I. Maibach (Eds), Marcel Dekker, New York, pp. 53-75. 

Generalized cutaneous candidiasis of newborns, mostly of mothers who suffered from vaginal candidiasis prior to delivery, often is associated with... 

Zelter et al. [126] compared iontophoretic and subcutaneous delivery of lidocaine and reported that although cutaneous bums were observed in two of the 13 patients for iontophoretic delivery, the majority of the subjects suffered only blanching or mild erythema of the treated site. Other studies also reported blanching and erythema of the skin [127], mild skin irritation [128], sensations of localized heat or cold [111], tingling and itching [126], and allergic contact dermatitis and vims activation [111]. 

Barry, B.W. Dermatological Formulation. Percutaneous Absorption, Marcel Dekker, Inc. New York, 1983 480. Flynn, G.L. Cutaneous and transdermal delivery processes and systems of delivery. In Modern Pharmaceutics, 3rd Ed. Banker, G.S., Rhodes, C.T., Eds. Marcel Dekker, Inc. New York, 1996 239-298. 

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