Hydrophilic compounds, effect

Another method of delivery of drug to the anterior segment of the eye that has proved successful is prodrug administration [144]. Since the corneal surface presents an effective lipoidal barrier, especially to hydrophilic compounds, it seems reasonable that a prodrug that is more lipophilic than the parent drug will be more successful in penetrating this barrier. 

Knipp GT, NFH Ho, CL Barsuhn, RT Borchardt. (1997). Paracellular diffusion in Caco-2 cell monolayers Effect of perturbation on the transport of hydrophilic compounds that vary in charge and size. J Pharm Sci 86 1105-1110. 

Morimoto et al. [33] demonstrated that the ocular absorption of hydrophilic compounds over a wide range of molecular weights could be increased by 2 and 10 mM sodium taurocholate and sodium taurodeoxycholate in a dose-dependent manner. The compounds were glutathione (307 Da), 6-carboxyfluorescein (376 Da), FTTC-dextran (4 kDa), and insulin (5.7 kDa). Of the two bile salts, sodium taurodeoxycholate was more effective. At 10 mM, this bile salt increased the permeability of 6-carboxyfluorescein from 0.02% to 11%, glutathione from 0.08% to 6%, FITC-dextran from 0% to 0.07%, and insulin from 0.06% to 3.8%. Sodium taurocholate, on the other hand, increased the permeability to 0.13%, 0.38%, 0.0011%, and 0.14%, respectively. Taurodeoxycholate was more effective than taurocholate in the nasal epithelium as well [202], This difference in activities can possibly be attributed to their micelle-forming capability, which is higher for taurodeoxycholate, a dihydroxy bile salt [190],... 

K Morimoto, T Nakamura, K Morisaka. (1989). Effect of medium-chain fatty acid salts on penetration of a hydrophilic compound and a macromolecular compound across rabbit corneas. Arch Int Pharmacodyn 302 18-26. 

The (3-blocker atenolol has received the most attention in studies of social phobia. Various reasons have pointed to using this agent over propranolol, which was the main dmg used in the early trials with nonclinical populations. Because atenolol is a polar, hydrophilic compound, it has a relatively poor ability to penetrate the blood-brain barrier. Thus, it is thought to have less potential to cause the depressogenic effects thought to be caused by more centrally acting agents, such as propranolol. 

It can be seen from Figure 3 that the molar mass distribution of the hydrophilic compounds (fraction I) is broad although they are eluted by RPC in a narrow zone (Fig. 2). Their reversed-phase chromatographic fractionation is thus based almost exclusively on their polarity, molecular size having no effect on the process. 

After permeation through the corneal epithelium, molecules should then permeate through the hydrophilic corneal stroma and the corneal endothelium before reaching the aqueous humor. Thus, while the corneal epithelium favors the penetration of lipophilic compounds, the hydrophilic stroma favors the permeation of hydrophilic compounds. The corneal endothelium monolayer is not sealed by paracellular zonulae occludentes. Consequently this layer has only a minimal effect on the overall permeability of the cornea. Overall, the cornea as a whole is tailored to allow the permeation of moderately lipophilic compounds (close to log P = 2) [40], On the contrary, the reported optimal lipophilicity for compounds penetrating through an isolated epithelial layer of the cornea was around log P=4 [41],... 

Thanou, M.M., Kotze, A.F. Scharringhausen, T., LueBen, H.L., de Boer, A.G., Verhoef, J.C. and Junginger, H.E. (2000a). Effect of degree of quatemization of A-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal Caco-2 cell monolayers. J. Control. Release 64 15-25. 

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g., buserelin). /V-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the para-cellular transport pathway. The absorption-enhancing effect was concentration dependent and reversible and dependent on the integrity of the intercellular cell contact zone. 

However, these general observations do not take into account the cyclical changes in the vaginal epithelium, which exert profound effects on vaginal absorption, especially for hydrophilic compounds. The permeability coefficient for the vaginal membrane (Pm) is equal to the sum of the permeability coefficient through the lipid pathway (P ) and the pore pathway (Pp) ... 

Other effects identified during cuticular uptake include the inhibition of surfactant uptake by an active, and the influence of cations in the cuticle on anionic compound diffusion. Different pathways have been postulated for lipophilic and hydrophilic compound movement. All these interacting factors require careful evaluation and identification of their effect on the generic concept of uptake through cuticular diffusion processes. Completely different analytical techniques may be required to elucidate these processes [41]. 

Enzymes as nature s catalysts are able to perform an outstanding array of regio- and stereoselective reactions. Therefore, as water is nature s solvent, it is not surprising that many biocatalytic reactions have been performed in the aqueous phase.However, in typical reactions, the substrates are limited to hydrophilic compounds because of a desire for reaction homogeneity. It should also be noted that, in most cases, the aqueous medium is a buffer solution of an ideal pH for the enzyme to function effectively. 

Liposomal systems also can form an effective drug reservoir in the upper layers of the skin. This is particularly useful for local skin therapy. Ethosomal carriers composed of phospholipid vesicular systems with alcohols are also effective at enhancing tran -dermal delivery of both lipophilic and hydrophilic compounds. The use of these ethosomes has been used in the delivery of minoxidil to the pilo-sebaceous section of the skin with better results than conventional liposomes. Similar results are reported in clinical studies with acyclovir in a topical therapy treatment of recurrent herpes labialis. Other application reports with ethosomes are patches containing testosterone (37). 

It is generally accepted that glycosides are more water-soluble than the respective aglycons. Attaching the glycosidic moiety to a molecule increases its hydrophilicity. This effect influences pharmacokinetic properties of the respective compounds, e. g., circulation, elimination and concentration in the body fluids. 

The data in Table 3.3 are remarkable in that despite the fact that the chemical and toxicological properties of the compounds studied vary widely, the effects of these chemicals on the toxicity of 2,4-D are predicted by Kqw values. The authors hypothesized that combinations of lipophilic and hydrophilic compounds would show synergistic effects resulting from membrane damage by lipophilic species and increased uptake of hydrophilic species. 

ACD has been associated with ethoxylated alcohol surfactants. Though not by themselves known to cause ACD, ethoxylated surfactants are polyethers and are easily air oxidized to hydroperoxides, peroxides, and carbonyl compounds (including formaldehyde and acetaldehyde), substances that do cause ACDJ22 251 The irritant components of surfactants and other chemicals present in formulated products facilitate the absorption of the ACD causing decomposition products of ethoxylated alcohols and thus exacerbate their effects. F61 This is yet another example of lipophilic compounds enhancing the absorption of hydrophilic compounds (the decomposition products of ethoxylated alcohols) and hence increasing the toxic effect beyond that predicted. 

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