Delivery to Intracellular Targets by Nanosized Particles - Intracellular Delivery: Fundamentals and Applications - page 75

from a few microns down to about 25 nm by the choice of preparation technique
and the phospholipid composition can also be chosen to provide adequate stability
(Szoka 1990 ). Other supramolecular assemblies based on amphiphilic molecules
have also be proposed for drug delivery. For example, oil-in- water micelles can be
used to solubilize lipophilic drugs for delivery. Of particular interest are micelles
formed from amphiphilic copolymers which are very stable to dilution (Kakizawa
and Kataoka 2002 ).
Emulsified systems have either an oil phase dispersed in an aqueous phase (o/w)
or an aqueous phase dispersed in an oil phase (w/o) with the aid of surfactants; o/w
systems are more suitable for biological applications. Despite the name, the so-
called microemulsions that are attracting much attention as delivery systems for
water-insoluble drugs have droplet sizes in the sub-micronic range. They are ther-
modynamically stable and form with a minimum of energy input, because they
contain a high proportion of surfactant and often a co-surfactant. On the other hand,
nanoemulsions, with a similar droplet size but a different internal structure are only
kinetically stabilized and require a large energy input to generate their small droplet
size (Heuschkel et al. 2008 ). Self micro-emulsifying drug delivery systems
(SMEDDS) have been developed recently in attempt to improve the oral bioavail-
ability of some water-insoluble drugs. A mixture of drug, oil, surfactant and co-
surfactant is administered and the micro-emulsion forms on dilution in the intestinal
fluid (Kyatanwar et al. 2010 ). Apolar lipids that are solid at physiological tempera-
tures can be formed into nanoparticulate systems with the aid of surfactant and an
energy input; these are called solid lipid nanoparticles (Wissing et al. 2004 ).
Nanoparticulate systems can also be prepared from macromolecules. Proteins
(e.g. albumin), poly (amino acids), polysaccharides (dextran, chitosan) and syn-
thetic polymers have all been used (Vauthier and Bouchemal 2009 ). Obviously for
drug delivery applications, the polymer chosen to prepare nanoparticles should be
biodegradable to non toxic products. Therefore, the polyesters poly (D,L-lactide)
(PLA) and poly (glycolide- co -lactide) (PLGA) are very often chosen as the basis
for nanoparticles. A particulate system can be formed from a single highly branched
polymer molecule: a dendrimer. Guest molecules can be attached by absorption or
covalent linkage. The most usual type of nanoparticle is a matrix of entangled poly-
mer chains. Depending on the affinity of the drug for the polymer, it can be included
in the matrix or adsorbed on the surface. These nanoparticles are sometimes
referred to nanospheres to distinguish them from another type of organization, the
nanocapsule (Couvreur et al. 2002 ). This is a reservoir form consisting of an oily
or aqueous core surrounded by a polymer shell. An appropriate drug molecule can
be dissolved in the core liquid.
The major role of a drug carrier is to modify the distribution of the drug, re-
routing it away from sites of toxicity and delivering more to the site of action. The
carrier can also protect a fragile molecule from degradation in physiological fluids.
It follows that the biodistribution of the carrier is primordial in determining its
range of application (Gregoriadis and Senior 1982 ). Simple colloidal particles are
“recognized” by the immune system in the same way as other foreign bodies such as
bacteria. That is, when they are introduced into the blood stream some components