Insulin, ocular absorption

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],... 

Individual members of the AG and SEFA family have been studied for their ability to promote the nasal and ocular absorption of peptide drugs in rats, mice, cats, dogs, and monkeys [1,6,10,53,54,84—90]. Dose-escalation studies were conducted in rats to determine the potencies of each of the AGs and SEFAs as enhancers for the ocular and nasal absorption of insulin and to determine the contribution of the alkyl chain and the sugar moiety. Insulin... 

Pillion, D.J., S. Hosmer, and E. Meezan. 1998. Dodecylmaltoside-mediated nasal and ocular absorption of lyspro-insulin Independence of surfactant action from peptide multimer dissociation. Pharm Res 15 1641. 

Pillion, D.J., et al. 1995. DS-1, a modified Quillaja saponin, enhances ocular and nasal absorption of insulin. J Pharm Sci 84 1276. 

In an investigation of the ability of different molecular substances to elicit ocular anaphylaxis when applied topically to the eye, Kahn et al. (1990) concluded that only substances having a molecular weight less than 3500 penetrate the conjunctival barrier. Therefore, systemic delivery via the ocular route seems to rely on overflow of the instilled dmg to the nasal cavity. Thus, the nasal mucosa contributed about 4 times more than the conjunctival mucosa to the systemic absorption of ocularly applied insulin (Yamamoto et al, 1989). Topically applied insulin administered chronically without surfactant seems to be nontoxic to the external human eye (Bartlett etal, 1994a). 

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