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Soluble macromolecular drug delivery systems

5/19/2009

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Soluble Macromolecules of both natural and synthetic origin have been used as drug carriers.  When compared with the particulate carriers, soluble macromolecules-

(a) encounter fewer barriers to their movement around the body and can enter into many organs by transport across capillary endothelium or (in the liver) by passage through the fenestration connecting the sinusoidal lumen to the space of Disse; 

(b) penetrate the cells by pinocytosis, which is a phenomenon universal to all cells and that, unlike phagocytosis, does not require an external stimulus; and 

(c) can be found in the blood many hours after their introduction (particulate carriers, in contrast, are rapidly cleared from the blood by the RES).

Macromolecular drugs, in general, can be divided into four types-

(a) polymeric drugs --- these represent macromolecules that themselves display pharmacological activity, and polymers that contain therapeutically active groups as an integral part of the main chain; 

(b) macromolecule-drug analog---- these are derivatives of drugs that require no separation from the macromolecule to fulfill their therapeutic actions; 

(c) macromolecular prodrugs (or macromolecule-drug conjugates)----these represent drugs that must be detached from the macromolecule at the target site(s) to exert their therapeutic effects and 

(d) noncovalently linked macromolecule-drug complexes.

The choice of a macromolecular carrier depends on the intended clinical objectives and the nature of therapeutic agents being used.  

In general, the properties of an ideal soluble carrier system include the following:

(a) the carrier and its degradation products must be biodegradable (or at least, should not show accumulation in the body), be nontoxic, and nonantigenic, and not alter the antigenicity of the therapeutic agents being transported. 

(b) The carrier must have an adequate drug-loading capacity; that is, the carrier must have functional groups for chemical fixation of the therapeutic agent.  

(c) The carrier must remain soluble in water when loaded with drug. 

(d) The molecular mass of the carrier should be large enough to permit glomerular filtration, but small enough to reach all cell types. 

(e) The carrier-drug conjugate must retain the specificity of the original carrier, and must maintain the original activity of the therapeutic agent until it reaches the targeted site(s). 

(f) The carrier-drug conjugate must be stable in body fluids, but should slowly degrade in extracellular compartments or in the lyososomes. 

(g) For lysosomotropic drug delivery, the macromolecule should not interfere with the pinosome formation at the cell surface, and subsequent intracellular fusion events.  

Conclusion:

Even though much work has been done already in the arena of Targeted DDS worldwide, not many products belonging to this category of Novel CRDDS have been explored.  

Hence, this area of research promises good business potential to manufacturers simultaneously giving patient compliance and effective therapeutic disease management benefits both to clinicians and patients.
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