Processing and Scale-up of Polymeric Nanoparticles - Intracellular Delivery: Fundamentals and Applications - page 448

prize and the speed compared to the freeze drying process. Spray drying required
addition of drying auxiliary compounds in the nanoparticle dispersion prior to be
processed in the spray drier (Müller et al 2000 ; Tewa-Tagne et al. 2007 ).

5 Integration of Required Functionalities

Challenging functions need to be associated to nanoparticles to be applied as drug
carriers. (1) The polymers should be non toxic, biocompatible and biodegradable if
the nanoparticles are designed for parenteral administration. This considerably
limits the number of suitable polymers (Vauthier and Bouchemal 2009 ). (2) Drug
association must be efficient. Many types of drugs are interesting to associate with
nanoparticle drug carriers. This includes small and large molecules as well as
hydrophilic and hydrophobic compounds. By combining the choice of polymer
composing nanoparticles and method of nanoparticle preparation almost all types
of drugs can be associated with nanoparticles based on their physico-chemical
properties. Use of cyclodextrin may improve drug loading if necessary (Duchene
et al. 1999 ). However, remaining challenges are to increase the amount of drug
actually associated with the nanoparticles (drug payload) and to reduce drug leak-
age from the nanoparticles before they reach the target site (Li and Huang 2008 ).
(3) Nanoparticles should transport active drug from the site of administration to
target site. In general, drugs associated with nanoparticles are well protected
against degradation. However, the most challenging and motivating part of the
development of nanoparticle drug carriers is to achieve transport to a specific target.
The method is to add specific equipments on the drug carrier surface. This equip-
ment has a dual role. First, it insures nanoparticles to remain well dispersed includ-
ing in biological media. Second, it confers specific capacity of the carrier to
recognize the pharmacological target. As obvious, one of these equipments is the
targeting moiety which allows the nanoparticles to recognize target tissue and target
cells with a high specificity. For instance, nanoparticles can be decorated with folic
acid to target cancer cells over-expressing the folic acid receptor at the cell surface
(Xia and Low 2010 ) but antibodies can also be used to this aim (Nobs et al. 2004a ).
Nanoparticle platforms with cyclodextrin and biotin residues at the surface were
created to facilitate further attachment of targeting moieties (Gref et al. 2003 ; Nobs
et al. 2004b ). In addition to the targeting moiety and for all nanoparticles designed
to target tissues outside the mononuclear phagocyte system, nanoparticle surface
must be masked with a protective coating conferring the nanoparticles the required
stability in the blood and a low capacity to activate the complement system
(Vonabourg et al. 2006 ; Vauthier et al. 2011 ). Typical material used are poly(ethylene
glycol) and polysaccharides (Li and Huang 2010 ; Romberg et al. 2008 ; Labarre
et al. 2005 ). The chain density should be high enough to hamper accessibility of the
nanoparticle surface to large proteins such as those implicated in the activation of
the complement system (Gref et al. 2000 ; Vauthier et al. 2011 ). With polysaccha-
ride coatings, an additional effect of the chain conformation was highlighted