Biomedical Engineering Reference
In-Depth Information
response to radiation, gamma irradiation may be used for end-stage
sterilization of nanoparticles discussed in this chapter. With end-
stage sterilization, the stability of the drug as well as particles has to
be ascertained.
PLA and PLGA polymers belong to the class of synthetic biode-
gradable polymers. Being synthetic in nature, as mentioned above,
they are available in various molecular weights, lipophilicities, and
rates of degradation. Thus, the duration of drug release can be
modulated based on the polymer choice. PLA and PLGA polymers
are degraded to lactic and glycolic acids in the presence of water due
to hydrolytic cleavage of the ester bonds in the polymer matrix. The
acids that are formed further catalyze the degradation of the parent
polymer, through a process known as autocatalysis and increase the
degradation rate with time [
14
,
15
]. As a result, these polymers are
degraded at the site of administration and can be easily eliminated
from the body. Owing to these properties, they are a preferred
choice for preparing nanoparticles intended for sustained delivery.
This chapter focuses on preparation of nanoparticles using the PLA
and PLGA family of polymers.
3.1.1 Selection of Carrier
Material
PLA and PLGA nanoparticles can be prepared by various methods
including emulsion solvent evaporation, emulsion solvent diffu-
sion, nanoprecipitation, and supercritical fluid technology, among
others. Of these, emulsion solvent evaporation technique is the
most commonly used and described in greater detail below.
Emulsion solvent evaporation involves two major steps, namely
emulsification followed by solvent evaporation. Emulsion formation is
accomplished by providing energy in the formof sonication or homog-
enization and solvent evaporation is achieved either by stirring at room
temperature or by increasing the temperature and reducing pressure.
Based on the nature of the drug, the emulsion solvent evaporation
method can be further divided into single emulsion method or double
emulsionmethod. Hydrophobic drugs are typically formulated using a
single oil-in-water (o/w) emulsion since the drug is soluble in the
inner organic phase along with the polymer. Hydrophilic drugs are
generally formulated using (water-in-oil)-in-water (w/o/w) double
emulsion method since the drug is insoluble in the organic phase but
soluble in the aqueous phase. Peptides, proteins, and nucleic acids
including plasmids can be entrapped into nanoparticles by the double
emulsion method. To reduce the degradation of peptides/proteins
(solid-in-oil)-in-water (s/o/w) methods may be employed. Figure
1
presents the general methodology for preparing o/w and w/o/
w emulsions. These two methods are further described below.
3.1.2 Emulsion Solvent
Evaporation Method
Single o/w emulsionmethod is used for loading hydrophobic drugs
in PLA/PLGA nanoparticles and is comprised of two principal
steps. In the first step, polymer solution is prepared in a volatile
Single Emulsion Method for
Hydrophobic Drugs
