AABRE: NETWORKING IN PUERTO RICO
PR-AABRE Researcher: Madeline Torres, Ph.D., Department of Chemical Engineering, UPR, Mayagüez Campus
Cluster: Drug Design and Delivery
Collaborators: Gustavo López, Ph.D. (UPR, M); Jorge Ríos-Steiner, Ph.D. (UPR, M); Joseph Bonaventura, Ph.D. (UPR, M); Carmen Cadilla, Ph.D. (UPR Medical Sciences Campus)
Mentor: Juan López-Garriga, Ph.D. (UPR, M)
Project Title: Molecular Studies of Protein Encapsulated in Soft Materials
“SOME DISEASES SUCH AS DIABETES, osteoporosis, and multiple sclerosis, in many instances, need to be treated with protein drugs. But proteins are very delicate—they lose their bioactivity easily. For example, in the gastrointestinal tract, the acids of the stomach will unfold the protein, and as soon as the folding is lost the protein is no longer biologically active,” says Chemical Engineering Professor Madeline Torres.
Torres and her research team are studying, at the molecular level, proteins encapsulated in biocompatible polymers. “To this date, most of the oral drug delivery research of peptides and proteins has focused on the material’s design and its release and protection properties. However, little has been achieved in the understanding of the interactions at the molecular level of the protein with the polymer. This information is also important when you are using encapsulated proteins for biosensor applications,” says Torres.
Soft polymers in the form of hydrogels and solgels could allow the controlled or sustained release of embedded medicines. But changes in the environment, for example changes in pH, ion concentration, electric or magnetic field, or even exposure to light, can influence polymer properties, which in turn influence the rate of drug release and bioactivity.
Bioactivity is also affected by the method of encapsulation. Torres likens the structure of a crosslinked polymer to that of a fence or a fishing net. “There are basically three ways to encapsulate the drug in polymers. We can open the structure, the net, of the polymer and insert the protein. [Because some polymers are pH sensitive, they swell in water.] Or we can create a network in the presence of the protein. In other words, we build it around the protein. Or we can chemically bond the protein to the polymer,” says Torres.
Each method has its problems.
“With the swelling method, if the polymer is again placed in water, the drug will get out. This is good for drug release, but for biosensor applications, we want it to be permanently encapsulated. By making the polymer around the protein, the monomers could be acidic or basic, so the solvent used could cause the protein to denature or lose its biological activity. And by chemically bonding the polymer to the protein, we are permanently encapsulating the protein; but if we use harsh chemicals, we could damage the protein.”
By learning how polymers react under conditions in the body, the researchers will contribute to the knowledge-base necessary to design better drug delivery devices or protein-based biosensors. Part of Torres’ research group is investigating the possibility of a protein-based biosensor that would detect the chemical associated with acid rain, hydrogen sulfide.
“This is one of the major health hazards in industry. People can’t smell it over a certain concentration. Recently, four people died because of a hydrogen sulfide accident.
“One of the hemoglobin proteins from the clam Lucina pectinata is capable of selectively recognizing hydrogen sulfide. Part of our work focuses on understanding the behavior and interaction of such hemoglobin with various polymer structures.
We are capable of synthesizing mutated structures of the heme proteins of Lucina pectinata to investigate changes in structure.”
Chemist Juan López-Garriga has the expertise in the preparation and spectroscopic characterization of mutated hemoglobins and their bioactive properties. Chemist Gustavo López simulates the thermodynamic behavior of the protein in aqueous solution and looks at how the mutation changes the behavior and its interactions with the polymer structure. And chemist Jorge Ríos is in charge of crystallizing the protein to determine its structure.
“We want to design a crystallization methodology and develop computational methodologies to simulate the protein in the polymer. We are investigating the morphology, structure, composition, and method of encapsulation to see the difference it makes in the bioactivity of the protein.”
madeline@ece.uprm.edu
