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Keywords
NANOPARTICLES, PRECIPITATION, APPARATUS TEST AND DEVELOPMENT, MODELLING, COMPUTATIONAL FLUID DYNAMICS, MIXING, TURBULENCE, POPULATION BALANCE, DRUG PRODUCTION

Multiscale modelling and development of process reactors for polymeric nanoparticle precipitation

Università degli Studi di Palermo
Abstract
Nanoparticle production is currently receiving a great research interest. This is due to the wide potential application field, which includes the production of adhesives, pigments, catalysts as well as of new effective drugs.
The present research programme is aimed at contributing to the field of nanoparticle production technology through the three main workpackages listed below.

1) Nanoparticle-production process and apparatus development. Five different precipitation reactors (standard stirred tank, static mixer, impinging stream , vortex and Couette cell reactors) will be experimentally investigated and critically compared by three of the research units.

2) Set up of advanced models aimed at simulating the performance of precipitation reactors. The models developed will be validated by comparison with the experimental data produced under workpackage 1. Once validated, the models developed will be employed for process and apparatus improvement and scale up.

3) One of the research units will set up a procedure for obtaining polymeric nanoparticles for targeted drug delivery. The procedure will be passed to the other units that in this way will be able to test the performance and viability of the precipitation reactors investigated and the modelling capabilities developed, on a real nanoparticle production process.

Principal Investigator
Alberto Brucato Università degli Studi di PALERMO
Research Objectives
The general aim of the project is that of developing advanced models and reliable apparatuses for the production of nanoparticles with targeted characteristics.
Modelling nanoparticle production processes is a very complex task, as it involves the set up on a number of sub-models aimed at describing the many elementary processes that contribute to the final result, at the many time and length scales involved.

A further complication arises from the number of processes devised so far for nanoparticle production, with the related need to set up specific sub-models. As a consequence, the choice was made here to orientate the efforts towards a specific class of nanoparticle production processes, namely that of polymeric nanoparticles for pharmaceutical applications. This choice was suggested by both the scientific interest in elucidating a still quite obscure range of phenomena as well as in view of the great application potential of such processes.

In comparison with standard preparations, nano-dispersions of pharmaceutically active organic compounds show impressive increase in dissolution rate, improvement in biological response, and the possibility of highly selective physiological action, which are achievable only with particle sizes in the middle or lower nanometer range (50 - 500 nm). The nanoparticles employed for therapeutic applications are often made of a polymeric structure that contains the active principle. Two main classes are >>>

Timescale
24 months
National and international background
As already specified, this project is aimed at devising processes, apparatuses and reliable simulation models for the set up of nanoparticle “process design” procedures and at testing the methodologies developed on a real benchmarck as the production of a new nanoparticle drug.

In order to increase the efficiency of therapeutic agents, the active principle should reach its target organ (or tissue) quickly and in sufficient amount, and it should remain there for a long time, avoiding distribution to other areas, thus reducing toxic effects (side effects). Unfortunately, drug distribution throughout the body is often slow, and the fraction of the drug that reaches the target is inadequate; doses must be increased and thus side effects become significant. This problem is typical of anti-tumour drugs. A recent innovation to increase drug selectivity towards cancer cells while reducing toxicity on normal tissues is the association of the drug with a nano-particulate carrier, usually made of polymer, able to deliver the drug and to shield it from degradation by the host .
These nanoparticles are classified either by the nature of polymer or by the preparation method (Couvreur et al, 1995) .
As said in the previous section, the objective of this research project is threefold: we intend to produce a nanoparticulate product well suited for optimal drug delivery in anti-tumour application, to set-up an efficient production process and to use the obtained >>>