Processing and Scale-up of Polymeric Nanoparticles - Intracellular Delivery: Fundamentals and Applications - page 434

PEO poly(oxyethylene)

PLL poly(lysine)

THF tetrahydrofuran

W/O/O water in oil in oil multiple emulsion

W/O/W water in oil in water multiple emulsion

W/O water in oil emulsion

1 Introduction

Nanoparticles have become common tools in research to improve drug efficiency
in vivo by a better control of the biodistribution. Proof of concept is now well estab-
lished and the use of nanomaterials to deliver drugs is about to revolution treatments
of severe diseases. It is noteworthy that a few systems have reached the clinics for the
treatment of cancer including TransDrug ® and one already marketed formulation,
Abraxane ® . Due to the variety of drug candidates, many polymer nanoparticles were
developed requiring different methods of processing. The aim of this chapter is to
summarize the different methods of processing polymer nanoparticles and to discuss
their performance regarding their potential and limitations for a scale up and for drug
encapsulation. The principles of the preparation methods will be described first.
Considerations about the scaling up will be presented in the next part followed by
general methods of treatments applied after preparation to purify, sterilize, dry and
condition the nanoparticles. The different functionalities which may be interested to
integrate in the nanoparticles will be discussed in the last part of the chapter.

2 Principles of Methods of Preparation of Polymer

Nanoparticles

Two classes of methods can be identified depending whether the obtaining of nano-
particles is achieved from a polymer solution or from an emulsion. The following
presentation of the general principles for nanoparticle preparation from polymers
will include this subdivision. Only methods of nanoparticle preparations from poly-
mers will be presented in this chapter. The methods based on polymerizations are
discussed in another chapter (See chapter by Nicolas and Vauthier in this topic ).
Schemes of the different types of nanoparticles are illustrated in Fig. 1 .

2.1 Methods Based on the Conversion of a Polymer Solution

into Nanoparticle Dispersions

Dilute solutions of polymers can be converted into nanoparticle dispersions taking
advantages of solubility properties of the dissolved polymer to precipitate as