drug delivery
(rus. доставка лекарственных средств otherwise адресная доставка лекарственных веществ; направленный транспорт лекарственных веществ)
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targeted transport of a drug to a given region of an organism, organ or cell.
Description
Classical pharmacology and pharmaceutics use the term "dosage form" to describe a method of drug administration into an organism, such as tablets, solutions for intravenous injections, eye drops, ointments, etc. The development of biomedical science and biotechnology led to the creation of new methods of drug packaging and delivery, such as liposomes, nanosomes (nanoscale liposomes) and other nanocapsules, as well as multifunctional nanoparticles, including magnetic nanoparticles (see magnetic nanoparticles for therapeutic use). The new and the conventional types of dosage forms differ in that the new technologies enable the targeted delivery of drugs to specific tissues, cells and even intracellular organelles. The essence of targeted delivery is that either the active pharmaceutical ingredient or, more often, its vehicle (vector, container) is modified by molecules capable of recognizing the receptors on the surface of target cells. The classic example is the folic acid molecule which is actively captured by tumour cells. Antibodies can act as universal molecules that recognize the surface of the target cell if it is known against which cell surface antigens they shall be designed. Extensive development of fundamental biomedical research provides the detailed antigenic expression profiles of cells, which allows one to distinguish different cell populations on the basis of the characteristics of their surface.
The targeting molecules on the surface of the vector leads to its concentration in a given region of the body (in the area of tumours, inflammation, ischemia, etc.) and drug delivery to this region. In contrast to the conventional administration of a drug and its distribution throughout the body, targeted delivery enables a reduction of the drug dose and minimizes its effects on healthy cells (side effects). In aggressive treatment of tumours the aspect of targeted delivery of highly toxic cancer drugs becomes particularly important.
In addition, it becomes possible to control drug release from the container. Thus, if the containers are nanoparticles with metal cores and polymer shells containing drug substances, the drug release can be induced by limited heating of the nanoparticles. This can be achieved by applying an alternating magnetic field or near-infra-red laser radiation, which is weakly absorbed by biological tissues, but well absorbed by metal nanoparticles.
After attaching to the target cell, the vector with the drug can be captured by the cell by means of endocytosis or by means of vector (liposome) membrane fusion with the cell membrane. In both cases, the drug is delivered into the cell and, with use of special techniques, could be targeted to the nucleus, mitochondria, endoplasmic reticulum and other organelles. The concept of intracellular drug delivery is under active development. In the implementation of the concept, a great value is given to knowledge of the signal sequences of proteins, which direct the proteins into various cellular structures. Equally important is the understanding of motor proteins that carry out the active transport of cargo over long distances within a cell and can be used to deliver drugs, genes and therapeutic nanoparticles.
The targeting molecules on the surface of the vector leads to its concentration in a given region of the body (in the area of tumours, inflammation, ischemia, etc.) and drug delivery to this region. In contrast to the conventional administration of a drug and its distribution throughout the body, targeted delivery enables a reduction of the drug dose and minimizes its effects on healthy cells (side effects). In aggressive treatment of tumours the aspect of targeted delivery of highly toxic cancer drugs becomes particularly important.
In addition, it becomes possible to control drug release from the container. Thus, if the containers are nanoparticles with metal cores and polymer shells containing drug substances, the drug release can be induced by limited heating of the nanoparticles. This can be achieved by applying an alternating magnetic field or near-infra-red laser radiation, which is weakly absorbed by biological tissues, but well absorbed by metal nanoparticles.
After attaching to the target cell, the vector with the drug can be captured by the cell by means of endocytosis or by means of vector (liposome) membrane fusion with the cell membrane. In both cases, the drug is delivered into the cell and, with use of special techniques, could be targeted to the nucleus, mitochondria, endoplasmic reticulum and other organelles. The concept of intracellular drug delivery is under active development. In the implementation of the concept, a great value is given to knowledge of the signal sequences of proteins, which direct the proteins into various cellular structures. Equally important is the understanding of motor proteins that carry out the active transport of cargo over long distances within a cell and can be used to deliver drugs, genes and therapeutic nanoparticles.
Illustrations
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Example of nanoscale medication delivery system built from block-copolymers — molecules with a hydrophobic nucleus containing medicine and a hydrophylic cover providing for biocompatibility of the carrier as a unit. Modification of surface with different vectors ensures delivery of the contained medication to target tissues and cells [1]. |
Authors
- Borisenko Grigory G.
- Shirinsky Vladimir P.
Sources
- Hoffman Allan S. The origins and evolution of «controlled» drug delivery systems // J. Contr. Release. 2008. V. 132. P. 153–163.
- Nanoparticulate Drug Delivery Systems / Ed. by D. Thassu, M. Deleers, Y. Pathak. — Informa Healthcare, 2007. — 352 p.