Pharmaceutical Manufacturing Handbook: Production and

and drug loading of gliadin nanoparticles are higher for hydrophobic drugs [89] .
Gliadin nanoparticles were targeted to Helicobacter pylori by chemical conjugation
of lectin glycoproteins to their surface, resulting in a twofold increase in inhibition
of bacterial activity compared to unmodifi ed nanoparticles [90] . Although gliadins
adhere to the mucosa, internalization of gliadin nanoparticles into cells has not been
reported. More defi nitive studies are required to fully understand the biological fate
of these particles.
5.4.3
SYNTHETIC BIODEGRADABLE POLYMERIC NANOPARTICLES 543
SYNTHETIC BIODEGRADABLE POLYMERIC NANOPARTICLES
A detailed description of the methods of polymerization and variables employed in
polymer synthesis are beyond the scope of this review and can be found in many
texts and review articles. The focus of this section is to provide an overview of the
properties and methods used to prepare nanoparticles from each class of synthetic
polymer.
5.4.3.1 Synthetic Polymers: Physical Properties and Methods of Preparation
of Nanoparticles
Poly(lactic acid) and Poly(lactide -co-glycolide) These poly - hydroxy acids are
approved for human use by the Food and Drug Administration (FDA) and have
been widely used to prepare biodegradable nanoparticles. PLA exists in optically
active and inactive forms and is a semicrystalline, hydrophobic molecule that
degrades in the body over a period of months. Conversely, poly(glycolic acid) is
amorphous and hydrophilic and degrades more rapidly than PLA. In aqueous
media, these polymers degrade by random hydrolysis of ester bonds that is autocatalyzed
in acidic media to form lactic and glycolic acids [91] . The factors that affect
the rate of hydrolytic degradation include type and composition of the polymer
backbone, nature of pendent groups, molecular weight, pH, enzymes, and geometry
of the delivery device.
The preparation and characterization of PLA and PLGA nanoparticles have
been extensively reviewed elsewhere [92, 93] . Various techniques may be used to
prepare PLA and PLGA nanoparticles, including simple and multiple emulsions,
nanoprecipitation, gas antisolvent method, supercritical fl uid technology, coacervation/phase
separation, and spray drying [91] . Briefl y, in the single - emulsion method,
an organic solution of the polymer and drug is emulsifi ed with an aqueous solution
of surfactant such as polyvinyl alcohol (PVA). While PLA and PLGA nanoparticles
containing hydrophobic drugs are prepared by the two - phase emulsion method, a
w/o/w multiple - emulsion method is needed to encapsulate hydrophilic drugs. In the
phase separation method, the addition of a nonsolvent precipitates or coacervates
the polymer from solution to encapsulate the drug. The experimental variables for
each protocol can be altered to infl uence the physicochemical properties, such as
particle size, particle size distribution, morphology, and zeta potential [93] . The
release of encapsulated drug from PLA and PLGA nanoparticles may occur by a
combination of diffusion and polymer degradation at a rate that is infl uenced by
properties of the polymer and nanoparticles and the environment. The surface of