In vitro penetration

Keywords Transdermal drug delivery Skin toxicity Microdialysis In vitro permeation In vitro penetration... 

While Franz-type diffusion cells are commonly used to assess in vitro penetration of compounds across the skin, they have also been used for the assessment of compound permeability across the buccal mucosa [19, 71, 104], In this system, buccal mucosa is sandwiched between two chambers, and compound solution is added to the donor chamber with compound-free buffer in the receptor chamber. The receptor chamber is then periodically sampled to assess the amount of compound that has permeated the tissue over time. 

Le Bran PPH, Fox PLA, de Vries ME, Bodde HE (1989) In vitro penetration of some /3-adrenoceptor blocking drugs through porcine buccal mucosa. Int J Pharm 49 141-145... 

Mehta M, Kemppainen BW, Stafford RG (1991) In vitro penetration of tritium-labelled water (THO) and [3H]PbTx-3 (a red tide toxin) through monkey buccal mucosa and skin. Toxicol Lett 55 185-194... 

They have been shown to be clearly effective in promoting the absorption of large molecules the in vitro penetration of some proteins was typically l%-3% but the addition of an appropriate absorption enhancer increased this to ca. 10% [13]. 

Musson, D., Bidgood, A., and Olejnik, 0. In vitro penetration and metabolism studies of prednisolone phosphate, disodium and prednisolone acetate across the cornea of rabbits. Pharm. Res. 6(suppl) S175, 1989. 

Bodde, H. et al., Visualisation of in vitro penetration of mercuric chloride transport through intercellular space vs. cellular uptake through desmosomes, J. Controlled Release, 15, 227, 1990. 

The presumed simplicity of in vitro penetration assays has led to their universal acceptance for preclinical and other screening purposes. However, they do not mimic human exposure in some important areas. Excised skin must often be stored prior to us and thus retains only some enzymatic activity. In intact skin, chemical penetrating the epidermis would enter the circulation through vessels and lymphatics located just below the epidermis. In excised full-thickness skin, the dermis is also involved in absorptive process. Storage conditions and procedures for preparing the tissue may affect skin absorption and metabolism. This is no opportunity to qualify key aspects of penetration cell turnover and desquamation and rub off. 

Ogiso T, Iwak IM, Hirota T, et al. Comparison of the in vitro penetration of propiverine with that of terodiline. Biol Pharm Bull 1995 18(7) 968-975. 

Manganaro AM, Wertz PW. The effects of permeabilizers on the in vitro penetration of propanolol through porcine buccal epithelium. Mil Med 1996 161 669-72. 

There are few published data on the percutaneous absorption of sunscreens through human skin (239,242-248). Most of the information came from in vitro penetration studies or by estimation from the amount recovered in the stratum corneum after tape stripping. The rationale for using the latter method (often referred to as the "reservoir technique") is based on the finding by Treffel and Gabard (248)that a linear relationship exists between the drug concentration in the stratum corneum and its in vivo percutaneous absorption. 

Zavala, F., Flollingdale, M. R., Schwartz, A. L., Nussenzweig, R. S., and Nussenzweig, V. (1985). Immunoradiometric assay to measure the in vitro penetration of sporozoites of malaria parasites into hepatoma cells. ]. Immunol. 134,1202-1205. 

Piras, M. M., Henriques, D. and Piras, R. (1987) The effect of fetuin and other sialoglyco-proteins on the in vitro penetration of Trypanosoma cruzi trypomastigotes into fibroblastic cells. Mol. Biochem. Parasitol. 22 135-143. 

Ogiso, T, Ito, Y, Iwaki, M., and Atago, H. (1986). Absorption of indomethacin and its calcium salt through rat skin effect of penetration enhancers and relationship between in vivo and in vitro penetration, J. Pharmacobiodyn., 9 517-525. 

Incorporation of CysA in both liquid crystalline formulations enhanced the in vitro penetration of the peptide in the skin, probably due to the action of monoolein (in combination with oleic acid in the case of hexagonal phase) as a penetration enhancer [60]. Several differences between the two liquid crystalline phases were detected (Fig. 12.16). The cubic phase increased the penetration of CysA in the SC and [E -b D], but did not influence the percutaneous delivery of the peptide compared with the control formulation. The hexagonal phase increased the penetration of CysA in the [E -b D] as well as its percutaneous delivery. No enhancement of the peptide concentration in the SC was observed when the hexagonal phase was used, since the increased penetration of CysA was into deeper skin layers and through the skin. Whereas the cubic phase formulation favored retention of CysA in the skin in vitro, the hexagonal phase favored its penetration into deeper skin layers and its percutaneous delivery. 

Fig. 12.18 In vitro penetration of CysA in the SC and [E + D] at 6 and 12 h following its topical application using the hexagonal phase nanodispersion or the control formulation. SC stratum comeum, [E + D] epidermis (without SC) plus dermis,...

Li et al. (2001) investigated the effects of eucalyptus oil on percutaneous penetration and absorption of a clobetasol propionate cream using vertical diffusion cells. The in vitro penetration of the cream containing 0.05% clobetasol propionate through mouse abdominal skin was detected at 2,4,6, 8, 10, and 24 h (cumulative amount Q, pg/g) and at steady state (/, pg/cm /h). The quantity of clobetasol propionate within the whole stria of skin after 24 h (D, pg/g) was measured too. Eucalyptus oil was able to increase Q and J, whereas D was not influenced in that way, which indicates that eucalyptus oil would increase clobetasol propionate percutaneous absorption and cause unwanted side effects. 

As L-isoleucine showed a competing effect with B CD in in vitro penetration study in Figure 3, it was examined in absorption study in beagle dogs (lOe). C increased linearly with the dose of L-isoleucine in the combination of the complex L-isoleucine, AUC also increased in a similar way. 

Barbero AM, Frasch HF (2009) Pig and guinea pig skin as surrogates for human in vitro penetration studies a quantitative review. Toxicol In Vitro 23 1-13... 

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