Page 131 - Book Hosokawa Nanoparticle Technology Handbook

2.6 NANOPARTICLE DESIGN FOR DDS FUNDAMENTALS
a surface modification with polyethylene glycol. So The technique to prepare nanospheres using poly-
far they are approved only in the Western countries. mers as a starting material is also important. As those
One of other nanoparticles of phospholipid-type is polymers are usually water-insoluble, it is needed to
a lipid emulsion. This is also a colloidal dispersed sys- dissolve them in an organic solvent to make emul-
tem, with about 200 nm particles of soyabean oil sion and then to evaporate the solvent off to form
emulsified with phospholipid, shown in Figure 2.6.2. nanospheres in the system. These methods are char-
To prepare the colloidal-dispersed system, a high- acterized by their evaporation techniques of solvent
pressure homogenizer is usually used. The submicron- (Table 2.6.1). One of the nanosphere preparation
sized particles having narrow particle size distribution methods in which polylacticacid-glycolicacid copoly-
are prepared with controlling the pressure in the sys- mer (PLGA), a typical biodegradable polymer, is used
tem, as a result of collisions between particle/particle has been investigated in the author’s laboratory. Two
and between particle/wall. Mantongohlin homoge- techniques were developed: the emulsion solvent dif-
nizer is a typical apparatus used for a long time and fusion method and the phase separation in oil method.
Microfluidizer and Nanomizer are also available. The two types of emulsion solvent diffusion meth-
As mentioned above, this lipid-emulsion formula- ods: in water [7] and in oil [8] have been developed.
tion has been used as an injection satisfactorily to In the former method, PLGA is dissolved into the
supply nutrition. Recognizing the safety of this for- admixture of acetone, which is miscible with water,
mulation, DDS formulation, which delivers drug to and dichloromethane, which is immiscible with water.
the aimed region by enclosing it in the oily area of When it is added to the Polyvinylalcohol (PVA) solu-
core, has been developed in Japan (lipo-formulation). tion, acetone can diffuse into the water phase rapidly
As the drug is enclosed in the oily part of particle, it and form the submicron-sized polymer droplet in the
is limited to the hydrophobic one. These formula- water phase. The following evaporation of the organic
tions used currently are prostaglandin (PGE ), dex- solvent in the polymer droplet at reduced pressure
1
amethasone, and flurbiprophen. The latter two leads to formation of suspension of polymeric nanos-
formulations are derived into dexamethasone palmi- pheres. In the latter one, oil was used as the continu-
tate and then into flurbiprophen akycetyl to increase ous phase of the emulsion based on the same
its hydrophobicity. It has been reported that these principle. The rate of enclosing water-soluble materi-
preparations show good collectiveness to the als in this method improves 10 times more than that in
disease regions. water system. In addition, to improve the enclosing
capacity, the phase separation in oil method [9] and
(2) Polymeric nanoparticles the modified phase separation method with combina-
Polymeric particles are more rigid than the phospho- tion of phase change in the emulsion system [10] have
lipid particles. Thus, size control of polymeric been developed. The latter method can improve the
nanoparticles is not easier than in the case of phos- encapsulation rate of water-soluble material of insulin
pholipid nanoparticles. The preparation method of and also can decrease the burst release phenomenon
polymeric nanoparticles is classified into two types by at the initial stage of release test.
the starting material: monomers or polymers, and To prepare the suitable polymeric nanoparticles for
there are the individual preparation methods in each drug delivery, the suitable choice of the polymeric
case. In common with other particles, it is important to materials of the particle and techniques by consider-
enclose a drug to form the capsule of drug efficiently. ing the properties of the drug entrapped is required.
Polyalkylcyanoacrylate nanoparticle is one of the
typical polymeric nanoparticles, prepared from
monomers with simultaneous polymerization. It uses Table 2.6.1
the high reactivity of alkylcyanoacrylate, a monomer, Preparation methods of polymeric nanosphere.
in the existence of water. Since Couvreur et al. [4]
first reported this method, this type of polymeric a) Evaporation method: Evaporation of the good solvent
nanoparticles has been investigated and developed for the polymer under a reduced pressure
mainly in Europe. In the typical procedure of this b) Good solvent extraction method: Extraction of good
method, alkylcyanoacrylate monomers are added into solvent for the polymer by adding the good solvent to
hydrochloric acid solution containing a surface-active the continuous phase
agent (surfactant) under mixing. On the other hand, Al c) Poor solvent adding method: Adding a poor solvent,
Khouri-Fallouh et al. [5] showed that nanocapsules, which is miscible with the good solvent, for
enclosing drugs perfectly, were produced from precipitation of polymer
monomers (isobutylcyanoacrylate) by applying the d) Solvent diffusion method (in water and oil):
interfacial polymerization technique. It was found Spontaneous diffusion of the good solvent to the
that water-soluble substances can be enclosed by continuous phase
applying the same interfacial polymerization and by e) Phase separation method in oil: Phase separation in
using aqueous drug solution as the dispersed phase in the good solvent diffusion into the continuous phase
the system [6].

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