Monoclonal antibodies parenteral administration

Monoclonal antibody therapy (MAT) makes use of all the major features of the immune response. It involves vaccination/ immunization, albeit in experimental animals, to induce the desired specific immune response. It exploits the high specificity, selectivity, and affinity of the antibody CDR toward the target antigen to be recognized, highlighted, inactivated, or eliminated, using the characteristics of the Fc portion of an immunoglobulin to facilitate the means for such inactivation or elimination and for selection of appropriate effector mechanisms. Finally, MAT represents a modern form of serotherapy, in which parenteral administration of whole serum or Ig preparations has been replaced by recombinant antibody molecules of a defined specificity. 

In this book, the term dmg delivery system (DDS) is used as a general term to denote any type of advanced delivery system. Conventional dmg delivery systems are simple oral, topical or injection formulations. A DDS, as used here, represents a more sophisticated system which may incorporate one, or a combination, of advanced technologies such as rate-control, pulsatile release or bioresponsive release to achieve spatial and/or temporal delivery. A dmg delivery and targeting system (DDTS) specifically describes an advanced delivery system that incorporates some type of specific targeting technology (such as, for example, monoclonal antibodies) such systems are currently most advanced for use in the parenteral administration of dmgs. Also, rate-control and dmg targeting are treated as two separate issues in this book and are dealt with in detail in Chapters 4 and 5 respectively. 

Trehalose is used for the lyoprotection of therapeutic proteins, particularly for parenteral administration. Other pharmaceutically relevant applications include use as an excipient for diagnostic assay tablets for stabilization during the freeze-thaw and lyophilization of liposomes and for stabilization of blood cells,cosmetics, and monoclonal antibodies. Trehalose may also be used in formulations for topical application. ... 

An alternative option for the treatment of hypertension was pursued with direct renin inhibitors. [21 ] Monoclonal antibodies, directed against renin, had shown blood pressure lowering properties in animal models. However, due to their immunogenicity and mandatory parenteral administration, they proved not suitable for long term treatment. 

The parenteral route is used for the administration of small molecules as well as for large molecules (proteins, monoclonal antibodies, vaccines, immunoglobulins). 

Problems can consist in the chemical and colloidal stabihty, eg upon oral administration, and in the low permeation through cellular membranes. For this reason vesicles are mostly administered parenterally, ie intravenously, subcutaneously, or intramuscularly. Their tissue specificity is first confined to the cells of the reticuloendothelial system which recognizes them as foreign microparticles and transports them to liver and spleen. Their biodistribution can be regulated by surface modification, eg by placing PEO stealth systems) or monoclonal antibodies site-specific targeting) to the vesicle smface. By this means their residence time and bioavailablity can be increased (211). 

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