Peptides absorption

WA Ritschel. Microemulsions for improved peptide absorption from the gastrointestinal tract. Methods Find Exp Clin Pharmacol 13 205-220, 1991. 

Wikman-Larhed, A., Arursson, P., Co-cultures of human intestinal goblet (HT29-H) and absorptive (Caco-2) cells for studies of drug and peptide absorption, Eur. J. Pharm. Sci. 1995,... 

Forbes B, Wilson CG, Gumbleton M (1999) Temporal dependence of ectopepti-dase expression in alveolar epithelial cell culture implications for study of peptide absorption. Int J Pharm 180(2) 225-234... 

Similarly, the 4-methoxy-2-naphthylamides of Leu, Ala, Arg, and Glu (6.1, R=side chain of amino acid, R =MeO) were used to assess the type and activity of aminopeptidase in homogenates of conjunctival, nasal, buccal, duodenal, ileal, rectal, and vaginal tissues from rabbits. This systematic comparison afforded a better understanding of the role of the aminopeptidase barrier in peptide absorption from oral vs. non-oral routes [18]. In a comparable manner, the y-glutamyltranspeptidase and dipeptidase activities were investigated in mammary tissue with the 4-nitroanilides of Leu, Met, Lys, Glu, and Asp (6.2, R=side chain of amino acid) [19]. 

Ahsan, E., ]. ]. Arnold, E. Meezan, and D. ]. Pillion. Sucrose cocoate, a component of cosmetic preparations, enhances nasal and ocular peptide absorption. Int J Pharm 2003 251(1-2) 195-203. 

TABLE 13.1. Factors influencing protein and peptide absorption... 

Touitou, E. 1992. Enhancement of intestinal peptide absorption. J Control Release 21 139. 

Lee, V.H.L. 1990. Protease inhibitors and permeation enhancers as approaches to modify peptide absorption. J Control Release 13 213. 

Yamamoto, A., and S. Muranishi. 1997. Rectal drug delivery systems—Improvement of rectal peptide absorption by absorption enhancers, protease inhibitors and chemical modification. 

In order to overcome these issues, various noninvasive routes are tested for the delivery of peptides. The oral mucosa due to its high vascularity, avoidance of hepatic first-pass metabolism, and the absence of degradative enzymes normally present in the GI tract has been explored as a suitable route for peptide delivery. Several studies of peptide absorption through the oral mucosa have been conducted, and the results have been impressive in some cases, and not in the others. The development of mucoadhesive systems for buccal and sublingual delivery has increased the absorption and bioavailability of peptides, and various formulations have been developed using these systems. 

Fatty acid esters would be predicted to have little irritation or toxic effects. Ex vivo permeability studies conducted in porcine buccal mucosa showed significant permeation enhancement of an enkephalin from liquid crystalline phases of glycerine monooleate [32]. These were reported to enhance peptide absorption by a cotransport mechanism. Diethylene glycol monoethyl ether was reported to enhance the permeation of essential oil components of Salvia desoleana through porcine buccal mucosa from a topical microemulsion gel formulation [33]. Some sucrose fatty acid esters, namely, sucrose laurate, sucrose oleate, sucrose palmitate, and sucrose stearate, were investigated on the permeation of lidocaine hydrochloride [34], with 1.5% w/v sucrose laurate showing a 22-fold increase in the enhancement ratio. 

Mechanism of Peptide Absorption after Pulmonary Delivery... 

Additional factors influencing nasal peptide absorption include particle residence time and formulation pH and osmolarity. Ohwaki et al (10) measured the effect of solution pH and osmolarity on the intranasal absorption of secretin, a 27 amino acid peptide, in rats. Nasal secretin absorption, as measured by pancreatic secretion rates, was maximal at a formulation pH of 3.0 almost eight times greater than at neutral pH. Solution osmolarity had less effect overall on secretin absorption, maximal absorption occurring in a hyperosmolar saline solution of 0.462 M. 

Our observation that CMC lacked the ability to increase the systemic activity of desmopressin is consistent with the findings of Morimoto et al. (13), who reported that 1% CMC failed to enhance intranasal absorption of insulin, whereas, another bioadhesive agent, polyacrylic acid gel, effectively promoted insulin absorption. As the mechanism by which bioadhesives such as polyacrylic acid gel and carboxypolymethylene promote intranasal peptide absorption remains unclear, it is not possible to explain the demonstrated lack of similar activity by CMC. 

The increase in desmopressin activity observed in association with an increase in NBF due to coadministered histamine suggests that peptide absorption through the nasal mucosal membrane is in part, blood flow limited. Previous studies (15,fr3) have indicated that the duration of activity of desmopressin is directly related to the intranasal dose administered and resultant peak plasma desmopressin levels. These findings support our hypothesis that histamine enhanced desmopressin activity by increasing its mucosal absorption. 

Lee VHL (1990) Protease Inhibitors and Penetration Enhancers as Approaches to Modify Peptide Absorption. J Control Rel 213-223... 

Chao AC, Nguyen JV, Broughall M, Griffin A, Fix JA, Daddona PE (1999) In vitro and in vivo evaluation of effects of sodium caprate on enteral peptide absorption and on mucosal morphology. Int J Pharm 191 15-24... 

Florence, A. T., A. M. Hillery, et al. (1995). Nanoparticles as carriers for oral peptide absorption studies on particle uptake and fate. J Control Release 36 39-46. 

Fig. 3.4. Rates of Gly uptake from glycine and diglycine test solutions which are equivalent in Gly content (e.g. 20 mM Gly v. 10 mM Gly-Gly). The perfusion studies were done in the jejunums of five healthy human volunteers. (After Adibi, S. A. Kim, Y. S. Peptide absorption and hydrolysis. In Physiology of the gastrointestinal tract, ed. L. R. Johnson, 1981, with permission from Raven Press, New York.)...

Although, as described above, the vagina is permeable to many peptides and proteins, in most cases the bioavailability is insufficient for systemic therapy and is also highly variable. Penetration enhancers may be used to promote peptide absorption across the vaginal epithelium. However, less extensive investigations on the use of penetration enhancers for the vaginal route have been carried out in comparison to other routes, such as intranasal and transdermal (see Sections 9.7.1 and 8.6.1). 

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