Biomedical Engineering Reference
In-Depth Information
concentrations within the therapeutic window at the target site for
a prolonged period of time, thereby reducing the dosing frequency
and potential systemic side effects. Delivery systems such as
implants, scleral plugs, microparticles, and nanoparticles have
been developed for treating chronic ocular diseases that require
frequent drug dosing [
3
-
5
].
Nanoparticle-based delivery systems, particularly those based
on polymers, have shown great potential in ocular drug and gene
delivery over the past 10 years [
5
]. Depending on the polymer type
employed to design the nanoparticles, these systems can be classi-
fied based on polymer origin (natural, synthetic, semi-synthetic),
stability (biodegradable, non-biodegradable), charge (cationic,
anionic), lipophilicity (hydrophilic, hydrophobic, amphiphilic),
and release profile (sustained, controlled). Poly(lactide) (PLA)
and poly(lactide-co-glycolide) (PLGA) polymers that are synthetic,
biodegradable, and anionic are available in a range of molecular
weights and hydrophobicities. These polymers are biocompatible
with a long history of human use. They are present in the commer-
cially available microparticle products such as Lupron Depot
®
,
Decapeptyl
®
SR, and Nutropin
®
[
6
]. Hence, these polymers have
been widely used for synthesizing nanoparticles. PLA/PLGA nano-
particles can perform the dual function of releasing the drug in a
controlled manner while simultaneously protecting the remaining
drug still present inside the particle from enzymatic degradation
and physiological clearance, thereby providing sustained action.
Moreover, PLA/PLGA nanoparticles are amenable to surface func-
tionalization, allowing their use for targeted delivery [
7
,
8
].
Although PLA/PLGA nanoparticles have yet to be tested in clinical
trials for ocular diseases, there is growing evidence supporting their
use in targeted and sustained drug delivery in treating chronic eye
diseases. Hence, this chapter will primarily focus on the methods
for preparing PLA/PLGA nanoparticles for ocular drug and gene
delivery. Although several methods including those based on emul-
sions, nanoprecipitation, salting out, and supercritical fluid tech-
nology can be used for preparing PLA/PLGA nanoparticles,
emulsion solvent evaporation techniques are most commonly
used. Further, emulsion-based approaches are used for the com-
mercially available microspheres, suggesting scalability of this
method. Therefore, this chapter focuses on the preparation of
PLA/PLGA nanoparticles by the emulsion solvent evaporation
method. Emulsion solvent evaporation method can be employed
for entrapping both hydrophilic and hydrophobic drugs. It involves
two major steps, first being the emulsification of the drug in the
polymer solution followed by solvent evaporation to precipitate
the drug and polymer as nanoparticles [
9
]. Based on the nature of
the drug, this method has two primary variants, namely the single
