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Targeted drug delivery
Abstract
Under many circumstances, drugs used for treatment are required to act on site(s) located inside the cells of the tissues/organs in the multicellular animal systems. Even if the concentration of drugs is high in the circulatory body-fluids, their uptake by the cells across the barrier of the plasma membrane may be much below the optimally effective levels. The circulating high concentrations of such drugs may also inflict their own deleterious effects on the patient/animal. Also, delivery of toxins, genes, chemotherapeutic agents, antisense oligonucleotides and enzymes into cells for medicinal purposes has been limited due to low permeability of such molecules through the cell membrane. Therefore, it is desirable to have suitable vehicles for effective delivery of such molecules, which not only minimize the unnecessary exposure of the body to high concentrations of toxic materials but can also specifically deliver to the affected cells, such as: 1) Standard liposomes, 2) Long circulation liposomes, 3) Immunoliposomes, 4) Immunonano particles and immuno-conjugates, 5) Magnetic immuno-microspheres, 6) Targeted bacterial toxins and 7) Vitamin-mediated delivery, under discussion.
Hyaluronic acid is an important naturally occurring polysaccharide present in extracellular matrices. The network-forming, viscoelastic and the charge characteristics of hyaluronic acid are important to many biochemical functions of living tissues. Its involvement in many diseases such as cancer, arthritis and osteoporosis, and the fact that it has specific protein receptors present on the cell surfaces, has given new impetus in drug design and synthesis of hyaluronic acid-drug conjugates. As a general arrangement, the review will focus on structure and conformation of hyaluronic acid, its chemistry and chemical methodologies that have led to a number of important hyaluronic-drug conjugates.
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