Chapter category: Drug Design
Design and Synthesis of New Pro-Drugs to be Used with Carrier Red Blood Cells
Erythrocyte Engineering for Drug Delivery and Targeting
Edited by: Mauro MagnaniISBN: 0-306-47691-6
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Chapter authors:
S. ScarfÏ, G. Damonte and U. Benatti
Nowadays, increasing attention is devoted to new systems of controlled in vivo delivery of biologically active molecules, the primary aim being to overcome some disadvantages of conventional schedules of administration.1 Side effects are mostly critical for chemicals that display cytotoxic activities, as often observed with chemotherapic agents, especially antiviral and antitumoral drugs.
A promising strategy towards improvement of therapies with highly toxic molecules is the exploitation of autologous cells as bioreactors competent for the time- and site-controlled production of pro-drugs.
Within this frame, erythocytes have been proposed for two decades as potential carriers and bioreactors of medical interest.2 Internalization of many different molecules within red cells proved to be feasible by virtue of the properties of the erythrocyte membranes, whose elasticity and deformability allow the hypotonically induced opening of transient pores large enough to be crossed by externally placed macromolecules, before their closure in isotonic conditions.3. The erythrocytes so engineered have an in vivo life-span strictly comparable to that of unloaded ones when they are reinjected in the circulatory system of an autologous or compatible organism.
Once loaded, red cells can behave as slow delivery systems for molecules of pharmacological interest, improving their pharmacokinetic patterns and therapeutic performances.3-10 There are two major ways of achieving erythrocyte-based release of drugs: direct encapsulation of membrane-diffusable drug molecules or internalization of impermeant and more encapsulable pro-drugs susceptible to be metabolically converted by endogenous erythrocyte enzymes to membrane-releasable active drugs. Obviously, the specificity and kinetic properties of intra-erythrocytic enzymes involved in bioconversion reactions should dictate the choice of molecules that can be encapsulated in red blood cells to achieve the production of a specific drug. In all cases, the efficiency of the bioreactor, as measured by the output of the active drug, relies on several biochemical features including activity and substrate affinity of the bioconverting red cell enzymes and also patterns of exit of the drug across the membrane.
Additional chapters from this book:
Engineered Red Blood Cells as Circulating Bioreactors
P. Ninfali and E. Biagiotti
Over the last twenty years, enzymes encapsulated in red blood cells (RBC) have proven to be efficient bioreactors in the clearance of undesired molecules from the blood stream and have s...
Design and Synthesis of New Pro-Drugs to be Used with Carrier Red Blood Cells
S. ScarfÏ, G. Damonte and U. Benatti
Nowadays, increasing attention is devoted to new systems of controlled in vivo delivery of biologically active molecules, the primary aim being to overcome some disadvantages of conventional s...
Drug-Loaded Red Blood Cells for the Control of the Inflammatory Response: Selective Targeting of Nuclear Factor-kB (NF-kB)
R. Crinelli, A. Antonelli, M. Bianchi, L. Gentilini and M. Magnani
While the causes of inflammatory diseases remain unknown, transcription factors are increasingly being found to play a pivotal role in the development and maintenance of these pathologies. In ...
Erythrocytes as Carriers of Anthracycline Antibiotics in vitro and in
Victor M. Vitvitsky
Modern pharmacology largely relies on the use of drugs that selectively affect their target cells and tissues. The selectivity of antibacterial drugs of new generations is quite high. It comes...
Red Blood Cells as Carriers of Antiviral Agents
A. Fraternale, A. Casabianca and M. Magnani
In an attempt to overcome the problems of nucleoside analogue toxicity and of their limited efficacy and short plasma half-life we have investigated the possibility of using erythrocytes both ...
Engineered Nanoerythrocytes as a Novel Drug Delivery System
Sanjay Jain and N. K. Jain
Engineered nanoerythrocytes (nEs) as a novel controlled drug delivery system is a topic of interest to the pharmacist working in industry, research and development, academia, drug control admi...
Vaccination Strategy Using Red Blood Cells as Antigen Delivery System
Laura Chiarantini
The use of adjuvants is usually required to induce strong immunological responses to protein antigen. However, serious side effects preclude their use in human vaccines. Currently, the only ad...
Streptavidin-Mediated Coupling of Therapeutic Proteins to Carrier Erythrocytes
Vladimir R. Muzykantov and Juan-Carlos Murciano
Red blood cells (RBC) can provide a natural, safe and abundant carrier to prolong the life-time in the bloodstream and thus enhance the efficacy of certain therapeutic agents, while restrictin...
Targeting Drug Loaded Red Blood Cells
Mauro Magnani, Luigia Rossi and Giorgio Brandi
Targeting of drugs can be achieved in a number of ways usually conjugating the drug of interest with specific ligands or by engineering the properties of the carrier system. In this paper we s...
Towards Activated Release of Payloads from Carrier Erythrocytes
A.M. Rollan and A.P. McHale
Although the potential of erythrocytes as drug delivery vehicles has been suggested for some time, the applicability of this approach has been limited by the lack of a mechanism to achieve act...
Red Blood Cell Loading
Luigia Rossi, Sonja Serafini and Mauro Magnani
In this Chapter a selection of procedures for the encapsulation of a wide range of molecules into red blood cells is reported. Electroporation, drug-induced endocytosis, osmotic pulsing and hy...
