Purdue 'microspheres' offer promise for oral drug delivery

August 22, 2000

WEST LAFAYETTE, Ind. -- Chemical engineers at Purdue University have created a new class of non-toxic materials that might be used to deliver medicines orally instead of by injection.

The materials might be used to treat conditions for which medicines, such as insulin, currently cannot be administered orally because they are broken down in the acidic environment of the stomach. To get around this complication, the engineers have made drug-delivery "microspheres" about a millionth of a meter in diameter, or roughly one-hundredth the width of a human hair. The microspheres protect medicines from the harsh environment of the stomach until they can be released and absorbed in the intestines.

The key ingredient of the microspheres is a chemical compound called polyacrylic acid, which is best known as the "superabsorbent" filling in diapers, feminine hygiene and adult incontinence products. By grafting the polyacrylic acid with a plastic polymer called polyethylene glycol, the engineers produced the microspheres, which could be thought of as tiny sponges with a mesh-like structure that expands and contracts in response to changes in acidity.

The mesh is tightly woven while in an acidic environment, such as that of the stomach, and expands in chemically basic surroundings, such as those in the small intestine. In diapers and other products, the polyacrylic acid soaks up large volumes of liquid and retains the liquid, while keeping the surroundings dry. In drug delivery applications ,the microspheres are loaded with medicine and dried before use. Upon administration into the body they remain collapsed until reaching the small intestine, where the swelling mesh behaves like the expanding bars of a cage, allowing whatever is trapped inside to escape.

"Frankly, what we have is all the advantages of a new class of materials that absorb biological fluids rather fast," says Nicholas A. Peppas, Purdue's Showalter Distinguished Professor of Chemical and Biomedical Engineering, whose research group has produced these materials. Findings from the research will be presented on Aug. 23, during a meeting of the American Chemical Society in Washington, D.C., by co-inventor Petr Bures, a doctoral student in chemical engineering.

The polyacrylic acid now available commercially is not ideal for pharmaceutical applications because it is processed as a crude powder made of irregularly shaped particles that vary in size. Having an inconsistent size and shape makes it difficult to predict and control the performance of these particles and to form them into tablets for pharmaceutical purposes.

The microspheres that Peppas's group produced have a regular, spherical shape, which means their performance can be better controlled and predicted with mathematical models, and they are easier to process into pharmaceutical products.

Although other researchers have fabricated microspheres based on similar materials, the Purdue chemical engineers are the first to develop a way to produce them in water, meaning they are non-toxic and might be useful in pharmaceutical and biomedical applications, Bures says.

"The only way these microspheres have been produced up to now is using organic solvents, which may be bad for the body," Bures says. "The body is very sensitive to any kind of toxic material. So the best thing to do is to use water for the production of materials intended to deliver medicines; we have been able to do just that."

The technique was developed and optimized by Bures, Peppas and student David Henthorn, who was working on his undergraduate honor's thesis at the time and is now pursuing a doctoral degree.

"These microspheres may be used to absorb a lot of water, as is the case of a superabsorbent material, or to release drugs, if such drugs are incorporated into the system," Peppas says.

Polyacrylic acid has yet another property critical for use in drug delivery: it sticks to the mucosal lining of the upper small intestine, meaning it might be used to anchor drug-laden microspheres to the intestinal wall, while swelling and releasing medicines.

Writer: Emil Venere

Sources: Nicholas Peppas, 765-494-7944, peppas@ecn.purdue.edu
Petr Bures, 765-494-4080, bures@ecn.purdue.edu

Related Web sites: American Chemical Society meeting: http://www.acs.org/meetings/washington2000
Professor Peppas's Web page: http://ChE.www.ecn.purdue.edu/ChE/Fac_Staff/Fac.Staff/peppas/
Petr Bures's Web page: http://ChE.www.ecn.purdue.edu/ChE/Fac_Staff/Grads/bures/

ABSTRACT Molecular dynamics of pH-sensitive hydrogels based on poly(acrylic acid)

Petr Bures and Nicholas A. Peppas, Chemical Engineering, Purdue University

Polymers based on poly(acrylic acid) (PAA) exhibit properties such as pH-dependent swelling, outstanding mucoadhesive characteristics and the ability to protect proteins and peptides from proteolytic degradation, all of which are desirable for drug delivery. Polymer networks of PAA grafted with poly(ethylene glycol) chains of molecular weights between 200 and 1,000 were synthesized by free-radical solution polymerization. Fourier transform infrared (FTIR) spectroscopy was used to investigate the presence of interpolymer complexes between the hydrogens of the carboxylic acid groups present on the PAA backbone and the ether oxygens on the grafted PEG chains. The formation of complexes showed a profound dependence on the length of the PEG graft. The equilibrium swelling behavior of these ionic hydrogels containing hydrogen-bonding complexes, which are sensitive to the external environment, was examined as a function of pH. Networks containing the largest PEG grafts were the most responsive to pH changes of the swelling media.

NOTE TO JOURNALISTS: A copy of the research paper is available from Emil Venere.

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