Biomedical Engineering Reference
In-Depth Information
transfecting ocular cells, eyes treated with MNP did not show signs of inflammation nor did they
induce white blood cell infiltration, both intravitreally and subretinally [5]. Intraocular pressure in
MNP-treated eyes remained the same as phosphate buffered saline (PBS)-treated eyes, suggesting
that the particles did not disturb any intraocular meshwork [4].
Histological analysis of MNP-treated ocular tissue did not yield any signs of iron oxide tox-
icity by the nanoparticles [4]. MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
(MTT) cytotoxicity assays showed the biocompatibility of MNP coated with polyethylenoxide
copolymers, suggesting that these nanoparticles are safe for intraocular injection [4]. In addition,
the iron oxide was not shown to cause oxidative stress
in vivo
[2].
The use of uncoated MNP could lead to aggregation and oxidation
in vivo
; thus, natural, biocompat-
ible, and biodegradable polymers are used to coat the nanoparticles [4]. Adaptation of the surface of
the particle could enhance product delivery to tissues and could target specific tissues by the polymer
coat used on the MNP [4]. Since iron oxide is a component of the MNP, exposure to external magnetic
fields could be harmful to body tissues; however, these data were not provided [4]. In addition, iron
could damage photoreceptors in the eye, thereby causing a serious side effect [4,17]. However, the low
iron load in the MNP and the protective polymer coating prevented iron from leaking out into the tis-
sue and showed no great amplitude difference in electroretinography (ERG) waveforms as compared to
tissues injected with PBS [4]. Since MNP causes no major cytotoxicity issues
in vivo
for up to 5 months
postinjection, MNP is one of the safest nanoparticle gene delivery mechanisms currently available [2,4].
16.1.4 c
hItosaN
Chitosan, a biocompatible and nontoxic deacetylated form of chitin derived from crustacean shells,
is one of the least expensive and most widely used nanomaterial in ocular therapies [2,5]. The
positively charged surface of the nanoparticles helps them interact well with the negatively charged
corneal surface and has been successful in delivering drugs and genes to the ocular tissue [2,5].
Given these benefits, chitosan is a biomaterial that has different effects in different ocular tissues,
making it compatible in some and incompatible in others [2,5]. Topically, chitosan shows biocom-
patibility and efficient gene delivery with little-to-none tolerance issues nor any tissue necrosis up
to 24 h posttreatment [2]. However, chitosan induces acute inflammatory responses when injected
intravitreally [2,5]. The severe inflammatory response caused a vitreous haze and membranous
opacities caused by infiltration of a large number of monocytes to phagocytize the foreign poly-
saccharide-based chitosan nanoparticles, suggesting that the immunomodulatory hyalocytes in the
vitreous humor are particularly sensitive to chitosan [2,5]. There were signs of retinal degradation at
the sites of the most severe inflammation [5]. The dichotomy in the biological interaction of chitosan
with different tissues suggests that chitosan is a promising nanoparticle for topical ocular therapy
but a poor intraocular therapeutic nanoparticle.
16.1.5 p
olylactIc
-c
o
-g
lycolIc
a
cId
Polylactic-co-glycolic acid (PLGA) is a copolymer of polylactic acid (PLA) and polyglycolic acid
(PGA) [3]. This biodegradable, biocompatible copolymer is one of the most studied polymers and
is a popular choice for the treatment of choroidal neovascularization [2,3]. The ratio of PLA and
PGA in the synthesis of PLGA can be altered to change the therapeutic effects of the copolymer in
biological systems by changing the total surface area, rate of drug release, and rate of polymer deg-
radation [3]. Since PGA is synthesized using toxic solvents, improper formulations may cause toxic-
ity in biological systems [3]. Furthermore, PLGA can be synthesized by emulsification in acetone
and methylene chloride, also chemicals that may induce cytotoxicity [2]. However, dose-dependent
studies of PLGA in biological systems did not yield any signs of cytotoxic effects on ocular tissues
[2]. With no reports of cytotoxicity in the eye, PLGA remains one of the most widely used, FDA-
approved nanoparticles for experimental nanotherapies [2].
