Drug Design
Chapters
Prediction of Drug-Like Properties
Gisbert Schneider
Historically, computer-aided molecular design (CAMD) has focused on lead identification and lead optimization, and many innovative strategies have been developed that assist in improving the binding affinities of drug candidates to specific receptors. One such method, QSAR, has been d...
A Conceptual Framework
Gisbert Schneider
"It is no longer just sufficient to synthesise and test; experiments are played out in silico with prediction, classification, and visualisation being the necessary tools of medicinal chemistry." (L. B. Kier)1
Pathological biochemical processes withi...
Analysis of Chemical Space
Gisbert Schneider
A main goal of virtual screening is to select activity-enriched sets of molecules — or single molecules exhibiting desired activity—from the space of all synthetically accessible structures. Currently the most advanced HTS techniques allow for testing of ~105 comp...
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 schedules of administration.1 Side effects are mostly critical for chemicals that disp...
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 particular, the broad involvement of nuclear factor-kB (NF-
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 administrators and professionals. This Chapter presents an overview of the concept of controlled dru...
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 shown an ability to correct congenital metabolic disorders. Highly efficient methods of entrapment ...
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 as no surprise because most of them are specific inhibitors of metabolic pathways vitally impor...
Evolutionary De Novo Design
Gisbert Schneider
"GAs have been shown to be capable of describing extremely complex bahaviour in a range of application domains, including those of molecular recognition and design." (P. Willett)1
In the previous Chapters we have addressed some issues related to adaptive opt...
Modeling Structure-Activity Relationships
Gisbert Schneider
Traditionally, the design of novel drugs has essentially been a trial-and-error process despite the tremendous efforts devoted to it by pharmaceutical and academic research groups. It is estimated that only one in 5,000 compounds investigated in preclinical discovery research ever eme...
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 hypotonic hemolysis are described. Among the hypotonic hemolysis procedures, three different metho...
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 as a slow delivery system and as a targeting system for the release of drugs at specific sites. ...
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 restricting their accessibility to the extravascular compartment and thus reducing side effects. Methods f...
Synopsis and Perspectives
Guilherme Suarez-Kurtz
“P harmacogenetics deals with pharmacological responses and their modification by hereditary influences”. This definition, offered by Werner Kalow in the first book dedicated to pharmacogenetics,1 highlights the three pillars of this discipline: pharmacology, genetics and human diversity. Phar...
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 summarize results so far obtained with the use of erythrocytes, as targeting system. Autologous h...
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 active release of payloads from the system. The scope of this chapter will be to review development...
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 adjuvant that is licensed for use in human vaccines is alum. Red blood cells (RBC) can be used as ...
