Microparticle carriers of maximal uptake capacity by both M cells and non-M cells

Abstract

In a solvent extraction process for preparing microspheres of a biodegradable polymer, the improvement comprising: preparing a homogenized antigen-sucrose matrix and adding a solvent to the sucrose-antigen matrix to form a solution; preparing a solution of a biodegradable polymer by adding a solvent to the polymer; adding the biodegradable polymer solution to the antigen-sucrose solution; adding an oil to the polymer-sucrose-antigen solution to form an emulsion having a controlled viscosity that corresponds to a predetermined average particle size of distributions of microspheres of biodegradable polymers; centrifuging the emulsion of controlled viscosity and removing the supernatant to obtain microspheres of a predetermined range of particle size distributions of from about 0.5 to about 7.0 micrometers.In immunostimulating composition comprising an encapsulating-microsphere of the biodegradable polymer has an average particle size distribution such that the majority of the microspheres will be taken up by the villous epithelium section of the intestines of a mammalian subject when administered as a vaccine against diseases caused by entero-pathogenic organisms.A solvent extraction process for preparing microspheres of a biodegradable polymer. The process includes preparing a homogenized antigen-sucrose matrix and adding a solvent to the sucrose-antigen matrix to form a solution. Preparing a solution of a biodegradable polymer by adding a solvent to the polymer. Adding the biodegradable polymer solution to the antigen-sucrose solution. Adding an oil to the polymer-sucrose-antigen solution to form an emulsion having a controlled viscosity that corresponds to a predetermined average particle size of distributions of microspheres of biodegradable polymers. Centrifuging the emulsion of controlled viscosity and removing the supernatant to obtain microspheres of a predetermined range of particle size distributions of from about 0.5 to about 70 micrometers.<?insert-end id="INS-S-00001" ?>

Description

I. CROSS REFERENCE[0001]This application is a continuation-in-part of U.S. patent application Ser. No. 07 / 867,301 filed Apr. 10, 1992, now U.S. Pat. No. 5,417,986, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07 / 805,721, filed Nov. 21, 1991, now abandoned, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07 / 690,485 filed Apr. 24, 1991, now abandoned, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07 / 521,945 filed May 11, 1990, now abandoned, which in turn is a continuation-in-part of U.S. patent application Ser. No. 07 / 493,597 filed Mar. 15, 1990, now abandoned, which in turn is a continuation-in-part of U.S. patent application Ser. No. 06 / 590,308 filed Mar. 16, 1984, pending.II. GOVERNMENT INTEREST[0002]The invention described herein may be manufactured, licensed and used by or for governmental purposes without the payment of any royalties to us thereon.[0003]The file of this patent contains at l...

AI Technical Summary

Benefits of technology

[0013]One object of the invention is to provide a method for producing microparticles of biodegradable-biocompatible microspheres having an average particle size distribution that maximizes uptake of the microspheres by both M cells and non-M cells, either in the villous epithelium or in the Peyer's patches, follicle-associated epithelium so that, upon encapsulating antigens or other chemotherapeutic agents within these microspheres, large doses of antigen will not be required to achieve sufficient local concentrations in these regions of the intestines when these microparticles are used as carriers of immunogens for oral or other types of immunization.

[0014]A further object of the invention is to provide a method for producing microspheres composed of poly (DL-lactide-co-glycolide) having an average particle size distribution so as to maximize the uptake of these microspheres into the lymphoid tissue of the gut through uptake by both M cells and non-M cells, either in the villous epithelium or in the PP follicle-associated epithelium, in order to enable smaller doses of antigen to achieve sufficient local concentrations in these regions of the intestines when using the poly (DL-lactide-co-glycolide) as a carrier of immunogens for oral or other types of immunization.

[0015]A yet further object of the invention is to provide a method for producing an average distribution of particle sizes of the most stable or least biodegradable poly (DL-lactide-co-glycolide) having equal molar parts of polymerized lactide and glycolide (50:50 DL-PLG) so as to maximize uptake or microspheres of this copolymer by both M cells and non-M cells, either in the villous epithelium or in the PP follicle-associated epithelium when using this copolymer as a carrier of immunogens for oral or other types of immunization in mammals.

Problems solved by technology

It is apparent from past studies that a protective mucosal immune response can best be obtained by introduction of the antigen at the mucosal surface; however, parenteral immunization has not been an effective method to induce mucosal immunity.

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