Page 130 - Book Hosokawa Nanoparticle Technology Handbook

FUNDAMENTALS CH. 2 STRUCTURAL CONTROL OF NANOPARTICLES
the body, whenever the particles are fine enough. 2.6.2 Design of nano drug carrier
They are easily captured by the reticuloendothelial
system (RES) in liver and spleen. So, it is very diffi- A drug carrier in submicron size is called a colloidal
cult to increase their circulating time in the blood and drug delivery system [2]. Typical colloidal drug parti-
it is one of the most serious subjects for the research cles are categorized into the phosphor-lipid types
to escape out (avoid, bypass, circumbent) RES uptake. (liposome and liquid emulsion) and the polymeric
When liposome, which is one of the typical fine par- types (polymer nanosphere, nanocapsule, and poly-
ticles, is prepared with combination of polyethylene mer micelle). Figure 2.6.2 shows schematic diagrams
glycol-conjugated phospholipids and the usual phos- of the typical nano drug carriers.
pholipids, its blood circulation time is prolonged by
decreasing RES uptake. This liposome is called a (1) Nanoparticles with phospholipids
stealth liposome after a stealth fighter plane flying Phosphor-lipid is one of cell component, and lipo-
away from the radar [1]. some is a finer particle with a double-membrane
The drug administration method via absorption structure of phospholipids. It is usually prepared by
through a mucous membrane such as gastrointestinal the thin lipid layer hydration method. In this method,
mucosa, nasal mucosa, and lung mucosa, has phospholipids’ thin layer is formed at the bottom of
received a great attention as an alternative method of flask by removing organic solvent from the solvent
injection, as well as trans-dermal systems. In com- dissolving phosphor-lipid, and then the layer is
parison with the absorption trans-dermal system, the hydrated with a suitable buffer solution, in order to
absorption from the mucosa is very efficient, obtain phospholipids vesicles. There are some other
because the surface area of mucosa is about two hun- methods: the heating method to change dispersed
dred times larger than those of epidermia. However, phospholipids into liposome and the reverse layer sol-
some drugs cannot be absorbed from mucosa owing vent-evaporating method (REV method). The details
to their own characteristics: the high molecular are not here, but they are available in the special tech-
weight and hydrophilic or hydrophobic property. nical books [3].
Peptide drugs are the typical ones, which have these Liposome particle prepared in the thin lipid layer
inconvenient characteristics and require the new hydration method has a wide particle size distribution
dosage forms instead of injection. These are also and its average particle size is usually a few microme-
susceptible to enzymatic degradation on the mucosa. ters. This particle is relatively soft, so during prepara-
Fine particles are expected as a carrier to accomplish tion it can be sized down into the submicron range by
the drug delivery. For effective drug delivery, the the ultrasonic wave method or the extruder method.
choice of administration methods and the control of The probe-type ultrasonic apparatus is usually used for
the drug releasing properties with these particles are this purpose. In the extruder method, liposome sus-
very important. The suitable designs and selection pension is passed through a polycarbonate filter with
on their particle size, the type of material, and parti- objective-sized holes with a high pressure. It is possi-
cle structure are required for the effective drug ble to get particles with intended size, like 100, 200,
delivery. 400 nm, and so on.
There are many aspects for designing optimum for- There are some commercial products of liposomal
mulation and preparation with nanoparticle systems. systems such as Doxil (adriamycin), DaunoXome
In this section, the preparation methods and efficacy (daunorubicin), and AmBisome (amphoterycin). It has
of fine particles in drug delivery are shown, including been reported that these show a good accumulation
surface modification of nanoparticles for effective onto the disease regions, one of the targeting formula-
drug delivery. tions. Among them Doxil is the stealth liposome with

Phospholipid
Polymer matrix

Oil
phase

Polymeric
Liposome Lipid Emulsion
Nanoparticle
Figure 2.6.2
Various types of nanosized drug carriers.

106