30 December 2013

Drug delivery: biocomputer with printer

The biocomputer decides when to administer medications

ChemPort.Ru based on the materials of Chemistry World: Biocomputer decides when to administer drugsAmerican researchers have developed an enzymatic logic system, which in the future may find application for the release of drugs.

The presented work is the first artificial biomolecular system that can process a series of physiological signals without the use of electronics.

A logical system based on a biocomputer and processing biomolecular signals could radically change the delivery of a drug into the body. Using the surface of sensitive electrodes that respond to certain biochemical impulses, the personification of the therapeutic approach "for a specific patient" is getting closer to reality.

The disadvantage of drug-releasing systems was the slow and uncontrolled release of the pharmaceutically active component. In order to stimulate the release of the drug, various external factors were used, including temperature, pH and biologically active substances. Systems activated by biochemical signals are often complex and limited in application due to the fact that their operation requires a combination of both a receptor and a drug release system. The physical separation of these two components on separate electrodes could simplify the process.

Complementing their previous work with glucose-sensitive electrodes, Evgeny Katz and Shay Mailloux from Clarkson University, in collaboration with Jan Halamek from the University of New York at Albany, have developed a logical biomolecular system for the release of a pharmaceutically active component. An electrode coated with a redox-active alginate polymer film cross-linked with iron(III) ions and containing mechanically bound biomolecules performs the function of a drug-releasing element, and an electrode modified with pyrroloquinoline quinone [pyrroloquinoline quinone (PQQ)] acts as a biocatalytic electrode.

The system is highly selective because it responds only to specific combinations of biomolecular excitatory signals, which are processed by a carefully designed system of sequentially arranged logic gates. As a result of NADH oxidation, the biocatalytic electrode generates a negative potential and a reduction current. In turn, iron (III) ions are reduced to iron(II), the film becomes soluble and the biomolecules encapsulated in it are released. The use of NADH to initiate release is an important achievement, since NADH can be generated by numerous biocatalytic systems of the body, and this makes it possible to expand the application of the developed model system.


The system responds only to certain combinations of biomolecular signals

Katz says that the novelty of the presented approach lies in the release of the target molecule when certain signals are received, which could eventually be signals received from the patient's body. Katz emphasizes that this work represents for the first time a system combining biological calculations with the release of a biomolecule. Katz explains that the study demonstrates the use of biological computing, in other words, data processing using biochemical methods, to initiate the subsequent process. Such a process could be compared to connecting a computer to a printer. In this combination, the computer processes the information, and the printer prints the data. In fact, the biochemical system developed by the researchers works in this way.

A Prasanna de Silva, a quantum chemistry expert at Queen's University Belfast in the UK, describes the system as a rare example of a logical drug release. Andy Adamatzky from the University of the West of England in the UK echoes him, saying that the research conducted by scientists has opened up new areas of application for newly emerging calculation models. Researchers were able to transfer unusual methods of computing from an exclusively theoretical field to a live applied field, where ideas about unusual data processing and decision-making can be carried out with the participation of biomolecules and, in the future, be used to treat diseases.

Although the concept presented by the researchers is not yet ready for full-fledged medical use, work on improving its practicality is already on the way to implementation, Researchers are trying to use real biological fluids to accomplish this task.

Sources:
1. Mailloux et al., Model System for Targeted Drug Release Triggered by Biomolecular Signals Logically Processed through Enzyme Logic Networks, Analyst, 2013;
2. Mailloux et al., Biomolecular release triggered by glucose input – bioelectronic coupling of sensing and actuating systems, Chemical Communications, 2013.

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