Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
W. Strobe, M. E. Lamm, J. R. McGhee, and S. P. James. In Mucosal Immunity and Infections at Mucosal Surfaces, Oxford University Press, Oxford, 1988.
J. Mestecky and J. R. McGhee. Immunoglobulin A (IgA): Molecular and celular interactions involved in IgA biosynthesis and immune response. Adv. Immunol. 40:153–245 (1987).
S. W. Craing and J. J. Cebra. Peyer's patches: An enriched source of precursors for IgA-producing immunocytes in the rabbit. J. Exp. Med. 134:188–200 (1971).
S. M. Michalek, N. K. Childers, J. Katz, F. R. Denys, A. K. Berry, T. H. Eldridge, J. R. McGhee, and R. Curtiss. Liposomes as oral adjuvants. Curr. Topics Microbiol. Immun. 146:51–58 (1989).
M. J. Ostro. In Liposomes; From Biophysics to Therapeutics, Marcel Dekker, New York and Basel, 1987.
J. L. Wolf, D. H. Rubin, R. Finberg, R. S. Kauffman, A. H. Sharpe, J. S. Trier, and B. N. Fields. Intestinal M cells: A pathway for entry of reovirus into the host. Science 212:471–472 (1981).
M. E. LeFerve, J. B. Warren, and D. D. Joel. Particles and macrophages in murine Peyer's patches. Exp. Cell Res. 53:121–124 (1985).
M. E. LeFerve, A. E. Boccio, and D. D. Joel. Intestinal uptake of fluorescent microspheres in young and aged mice. Proc. Soc. Exp. Biol. Med. 190:23–27 (1989).
M. J. Hsu and R. S. Juliano. Interactions of liposomes with the reticuloendothelial system. Biochim. Biophys. Acta 720:411–419 (1982).
M. Stevenson, A. J. Baillie, and R. M. E. Richards. Quantification of uptake of liposomal carboxyfluorescein by professional phagocytes in vitro. A flow microfluorimetric study on the J774 murine macrophage cell line. J. Pharm. Pharmacol. 36:824–830 (1984).
A. Pusztai. Transport of proteins through the membranes of the adult gastrointestinal tract—a potential for drug delivery? Adv. Drug Deliv. Rev. 3:215–228 (1989).
M. Takada, T. Yuzuriha, K. Iwamoto, and J. Sunamoto. Increased lung uptake of liposomes coated with polysaccharides. Biochim. Biophys. Acta 802:237–243 (1984).
M. Dubois, K. A. Gilles, J. K. Hamilton, P. A. Rovers, and F. Smith. Colorimetriric method for determination of sugars and related substances. Anal. Chem. 28:350–356 (1956).
P. S. Chen, Y. Y. Toribara, and H. Warner. Microdetermination of phosphorus. Anal. Chem. 28:1756–1758 (1956).
H. Shotton and K. Ridgway. In Physical Pharmaceutics, Clarendon Press, London, 1974, pp. 205–220.
T. Hara, Y. Aramaki, S. Tsuchiya, K. Hosoi, and A. Okada. Specific incorporation of asoalofetuin-labeled liposomes into hepatocytes through the action of galactose-binding protein. Biopharm. Drug Dispos. 8:327–339 (1987).
J. S. Wassef, D. F. Keren, and J. L. Mailloux. Role of M cells in initial antigen uptake and in ulcer formation in the rabbit intestinal loop model of shigellosis. Infect. Immun. 58:858–863 (1983).
I. J. Fidler and A. J. Schroit. Recognition and destruction of neoplastic cells by activated macrophages: discrimination of altered self. Biochim. Biophys. Acta 948:151–173 (1988).
A. J. Schroit, J. W. Madsen, and Y. Tanaka. In vivo recognition and clearance of red blood cells containing phosphatidylserine in their plasma membrane. J. Biol. Chem. 260:5131–5138 (1985).
J. Conner, C. Bucana, I. J. Fidler, and A. J. Schroit. Differentiation-dependent expression of phosphatidylserine in mammalian plasma membranes: Quantitative assessment of outerleaflet lipid by prothrombinase complex formation. Proc. Natl. Acad. Sci. USA 86:3184–3188 (1989).
H. M. Pater, N. S. Tuzel, and R. W. Stevenson. Intracellular digestion of saturated and unsaturated phospholipid liposomes by mucosal cells. Possible mechanism of transport of liposomally entrapped macromolecules across the isolated vascularly perfused rabbit ileum. Biochim. Biophys. Acta 839:40–49 (1985).
M. E. LeFevre, D. D. Joel, and G. Schidlovsky. Retention of ingested latex particles in Peyer's patches of germfree and conventional mice. Proc. Soc. Exp. Biol. Med. 179:522–528 (1985).
J. Pappo and T. H. Ermak. Uptake and translocation of fluorescent particles by rabbit Peyer's patch follicle epithelium: A quantitative model for M-cell uptake. Clin. Exp. Immunol. 76:144–148 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tomizawa, H., Aramaki, Y., Fujii, Y. et al. Uptake of Phosphatidylserine Liposomes by Rat Peyer's Patches Following Intraluminal Administration. Pharm Res 10, 549–552 (1993). https://doi.org/10.1023/A:1018945902276
Issue Date:
DOI: https://doi.org/10.1023/A:1018945902276