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Purpose. The aim of the study was to evaluate the capacity of poly(isohexylcyanoacrylate) nanospheres to concentrate 3′-azido 3′-deoxythymidine (AZT) in the intestinal epithelium and associated immunocompetent cells, which are known to be one of the major reservoirs of the human immunodeficiency virus (HIV). Methods. The tissue concentration of 3H-radiolabeled AZT in the gastrointestinal (GI) tract was obtained 30 and 90 minutes after intragastric administration to rats at a dose of 0.25 mg AZT/100 g of body weight. The distribution along the intestine was determined. AZT concentrations in the lymph were obtained by lymphatic duct cannulation. Results. Unlike the solution, nanoparticles did concentrate AZT very efficiently in the intestinal mucosa, as well as in the Peyer's patches, and could simultaneously control the release of free AZT. Concentration in Peyer's patches was 4 times higher for nanoparticles, compared with the control solution. The tissue concentration was 30-45 μM, which was much higher than the reported IC50 of AZT (0.06-1.36 μM) and was regularly distributed along the gastrointestinal tract. Conclusions. Nanoparticles have been shown to be efficient in concentrating AZT in the intestinal epithelium and gut-associated lymphoid tissues, supporting the view that these particles may represent a promising carrier to treat specifically the GI reservoir of HIV.

Purpose. The potential of using lectin-modified polymerized liposomes as Peyer's patch targeted oral delivery vehicles was examined.

The permeability of peptides across rabbit jejunal epithelium (JE) and Peyer’s patches (PP) was compared. Kyotorphin (L-tyrosyl-L-arginine) was almost completely hydrolyzed during its membrane transport in both PP and JE, but [D-Arg2] Kyotorphin (L-tyrosyl-D-arginine) was less hydrolyzed in PP than in JE. Since the permeability of intact [D-Arg2] Kyotorphin was almost equal in PP and JE, no superiority of PP to JE was found for dipeptide transport. More intact fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA) and concanavalin A (FITC-Con A) were transported in PP than in JE. At both absorption sites, the transport of the intact FITC-Con A was superior to that of the intact FITC-BSA. Colchicine significantly reduced the total transport of the intact and degradation forms of both peptides and the reduction ratio was greater in PP than in JE. Accordingly, it was suggested that PP can be used as prominent absorption sites for polypeptides since they have lower peptidase activity and higher endocytosis activity than JE.

Uptake of the nonabsorbable marker 6-carboxyfluorescein was investigated both free and encapsulated in liposomes as a function of their surface charge and hydrodynamic diameter in rat Peyer's patch and nonpatch tissue. Significant uptake of the marker occurred only when encapsulated in liposomes consisting of at least 25 mol% phosphatidylserine and was highest in Peyer's patches. 6-Carboxyfluorescein encapsulated in liposomes equal to or greater than 374 nm was preferentially taken up by Peyer's patches. There was a trend to higher uptake in lower intestinal segments. These findings were supported by fluorescence microscopic observations. Uptake by Peyer's patches was specific for negatively charged liposomes as judged from competition studies.

To evaluate the usefulness of liposomes as a carrier for the targeted delivery of antigens to gut-associated lymphoid tissue, liposomal stability and uptake by rat Peyer's patches were investigated. Liposomes composed of distearoylphosphatidylcholine, phosphatidylserine, and cholesterol (DSPC-liposome), or dipalmitoylphosphatidylcholine, phosphatidylserine, and cholesterol were stable in acidic solution (pH 2.0), diluted bile, and pancreatin solution. Following the oral administration of liposomes to rats, rhodamine B-PE incorporated in the lipid phase of DSPC-liposomes was preferentially taken up by Peyer's patches in the lower ileum. The uptake of rhodamine B-PE from DSPC-liposomes larger than 374 nm in mean diameter was high. Orally administered DSPC-liposomes of a large diameter thus appear to serve effectively as a vehicle for delivering antigens to Peyer's patches.

The objectives of this study were (a) to compare the aminopeptidase activity in the Peyer's patches of the jejunum and ileum of the albino rabbit against that in the adjacent patch-free segments and (b) to determine the relative sensitivities of the aminopeptidase activity in the Peyer's and non-Peyer's patches to aminopeptidase inhibitors and penetration enhancers. The results indicated that the Peyer's patches were about equal in aminopeptidase activity in the jejunum and in the ileum but were only 20-30% as rich in aminopeptidase activity as their neighboring patch-free areas. Compared to non-Peyer's patches, the aminopeptidase activity in the Peyer's patches was not as sensitive to the inhibitory effect of amastatin. It was, however, much more sensitive to the inhibitory effect of puromycin and p-chloromercuribenzoate and was somewhat more sensitive to the inhibitory effect of Na deoxycholate, Na glycocholate, and polyoxyethylene-9-lauryl ether. Therefore, based on substrate preferences and on the relative sensitivity of aminopeptidase activity to inhibition by aminopeptidase inhibitors and penetration enhancers, the relative proportions of various aminopeptidases in the Peyer's patches and in the non-Peyer's patches are likely different.