Mouse skin, hairless

Fig. 4 Generalized permeation profile. From left to right the data are for n-butanol permeating hairless mouse skin at 20°, 25°, and 30° C respectively. Increasing temperature raises the flux (slope) and shortens the lag time. 

H. Durrheim, G. L. Flynn, W. I. Higuchi, and C. R. Behl. Permeation of hairless mouse skin. I Experimental methods and comparison with human epidermal permeation by alkanols. J. Pharm. Sci. 69 781-786 (1980). 

J.-C. Tsai, M. J. Cappel, N. D. Weiner, G. L. Flynn, and J. Ferry. Solvent effects on the harvesting of stratum corneum from hairless mouse skin through adhesive tape stripping in vitro. Int. J. Pharm. 68 127-133 (1991). 

N-Mannich derivatization has also been documented to improve skin delivery [91][92], In the case of theophylline (11.56) and 5-fluorouracil (11.58), a much improved solubility in water of the various N-Mannich bases examined was observed. To avoid breakdown, however, the prodrugs had to be dissolved in a polar nonaqueous solvent (isopropyl myristate) for pharmaceutical use. The delivery of theophylline and 5-fluorouracil through hairless mouse skin was, thus, accelerated approximately sixfold through use of the prodrugs 11.57 and 11.59, respectively. 

Chloroform can also permeate the stratum comeum of rabbit skin (Torkelson et al. 1976) and mouse skin (Tsuruta 1975). Percutaneous absorption of chloroform across mouse skin was calculated to be approximately 38 pg/min/cm, indicating that the dermal absorption of chloroform occurs fairly rapidly in mice. No reliable studies report the percutaneous absorption of chloroform in humans however, a few clinical reports indicate that chloroform is used as a vehicle for drug delivery (King 1993). Islam et al. (1995) investigated the fate of topically applied chloroform in male hairless rats. For exposures under 4 minutes, chloroform-laden water was applied to shaved back skin for exposures of 4-30 minutes, rats were submerged in baths containing chloroform-laden water. Selected skin areas were tape-stripped a various number of times after various delay periods. It appeared that there was an incremental build-up of ehloroform in the skin over the first four minutes. When compared to uptake measured by bath concentration differences, approximately 88% of lost chloroform was not accounted for in the stratum comeum and was assumed to be systemically absorbed. 

Walters and Olejnik s ( H) data on methyl nicotinate transfer through hairless mouse skin. All indicate maximal activity residing with the C22 ether. Not only do the latter two studies indicate a falling off in effectiveness as the chain length is increased to and Cia but they also indicate that the oleyl (unsaturated chain) ethers are more active than their saturated analogues. 

Particles from cationic lipids may also be useful for antisense therapy of skin disease — a nontoxic increase in the oligonucleotide uptake by cultivated keratinocytes and a sebocyte cell line has been reported [66]. Moreover, cationic dendri-mers also efficiently transfer reporter gene DNA to human keratinocytes cultivated in vitro. In the skin of hairless mice, in vivo transfection was possible with complexes, yet reporter gene expression was localized to perifollicular areas. Transfection, however, failed with the naked plasmid. For prolonged contact, biodegradable membranes coated with dendrimer/DNA complexes were used [67]. This hints at a follicular uptake of these complexes and indicates that gene transfection also may be possible with human skin, which has a thicker stratum comeum compared with mouse skin (eight to ten vs. two to three layers [58]). 

In the light of these observations and the newer trends in product formulation, it was decided to study the in vitro release and permeation of propranolol hydrochloride from various hydrophilic polymeric matrices using the cellulose membrane and the hairless mouse skin as the diffusion barriers and to evaluate the effects of some of the additive ingredients known to enhance drug release from dermatological bases. 

The in vitro diffusion studies for each sample were carried out by using the Franz diffusion cells with a diffusional area of about 1.76cm2. The acceptor compartment of the apparatus was filled with the buffer solution pH 6, USP [21], and maintained at 37 0.5°C via a circulating water system. The diffusion membrane (the cellulose membrane with a molecular weight cut-off point of 1000 or the hairless mouse skin) previously prepared was placed between die donor and the acceptor compartments of the assembly. An accurately weighed 4g of sample was then placed in the donor cell and the diffusion process was started. The solution in the acceptor compartment was continuously stirred with a small magnetic stirrer to maintain the sink conditions. Aliquots from the receptor cells were removed at 0.5,2,4, 8 and 24 h time intervals and replaced with equal... 

Permeation studies using hairless mouse skin... 

The Methocel matrix, formulation A, was further investigated using the hairless mouse skin as the diffusion barrier. Here the drug release was observed to be reduced significantly to 1.3mg/ (24h) compared with 11.75 mg/(24h) through the cellulose membrane. The formulation was further modified with the inclusion of... 

Table 6—Effect of DMSO on the permeability of propranolol hydrochloride from Methocel matrix diffusion experiment through hairless mouse skin...

Fig. 3—Diffusion profile of propranolol hydrochloride as a function of time (t) from Methocel matrix through hairless mouse skin , matrix+skin o, matrix (5% DMSO)+skin , matrix+skin soaked in DMSO for 1 h.

Table 7—Computed parameters for Methocel matrix diffusion data through hairless mouse skin (up to 12 h)...

Monti D, Giannelli R, Chetoni P, Burgalassi S. Comparison of the effect of ultrasound and of chemical enhancers on transdermal permeation of caffeine and morphine through hairless mouse skin in vitro. Int J Pharm 2001 229 131-137. 

Reagan-Shaw S, Afaq F, Aziz MH, Ahmad N. 2004. Modulations of critical cell cycle regulatory events during chemoprevention of ultraviolet B-mediated responses by resveratrol in SKH-1 hairless mouse skin. Oncogene 23 5151-5160. 

When investigating the effects of water on transdermal permeation, animal skin may yield results markedly different to human data. For example, hairless mouse skin is unsuitable for modeling human stratum corneum regarding hydration effects the murine skin, when hydrated for 24 h, became grossly more permeable than human skin membranes [8]. Thus water effects on skin permeability obtained using animal models need cautious assessment. 

Terpenes continue to be a popular choice as experimental enhancers for delivering materials across skin membranes. For example, L-menthol facilitated in vitro permeation of morphine hydrochloride through hairless rat skin [37], imipramine hydrochloride across rat skin [59], and hydrocortisone through hairless mouse skin [60]. Recently, niaouli oil was found to be the most effective of six essential oils in promoting estradiol penetration through hairless mouse skin [61]. It is noteworthy that there is currently little control on the topical use of most terpenes, and many aromatherapy oils and formulations contain appreciable quantities of these chemicals. Their excessive use offers potential for permeation of hazardous compounds from the same formulations into the skin some terpenes also have pharmacological activity. 

Many studies have employed phospholipids as liposomes (vesicles) to transport drugs into and through human skin. However, a few investigations have also employed phospholipids in a nonvesicular form as penetration enhancers. For example, 1% phosphatidylcholine in PG, a concentration at which liposomes would not form, enhanced theophylline penetration through hairless mouse skin [64]. Similarly, indomethacin flux was enhanced through rat skin by the same phospholipid and hydrogenated soybean phospholipids increased diclofenac permeation through rat skin in vivo. 

Bond, J.R., and B.W. Barry. 1986. Limitations of hairless mouse skin as a model for in vitro permeation studies through human skin Hydration damage. J Invest Dermatol 90 486. 

Sarpotdar, P.P., and J.L. Zatz. 1986. Evaluation of penetration enhancement of lidocaine by non-ionic surfactants through hairless mouse skin in vitro. J Pharm Sci 75 176. 

Monti, D., et al. 2002. Effect of different terpene-containing essential oils on permeation of estradiol through hairless mouse skin. Int J Pharm 237 209. 

It was shown that liposomes, due to their structure, have a retarding effect on the incorporated drug release. In early studies, Knepp et al. reported that progesterone release from agarose gel was faster than from liposomes embedded in the gel [29]. This retarding release behavior from liposomes was further confirmed by a lower drug transport rate as compared to the gel measured across hairless mouse skin [30], Another study by Foldvari et al. [8] examined the... 

Van den Bergh, B.A., et al. 1999. Elasticity of vesicles affects hairless mouse skin structure and permeability. J Control Release 62 367. 

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