Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants Page: 1
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OPEN 8 ACCESS Freely available online
Intraocular Pressure Changes: An Important Determinant
of the Biocompatibility of Intravitreous Implants
Ling Zou1, Ashwin Nair', Hong Weng', Yi-Ting Tsai', Zhibing Hu2, Liping Tang'*
1 Joint Program in Bioengineering, University of Texas - Southwestern Medical Center at Dallas and The University of Texas at Arlington, Arlington, Texas, United States of
America, 2 Departments of Physics and Materials Science and Engineering, University of North Texas, Denton, Texas, United States of America
Background: In recent years, research efforts exploring the possibility of using biomaterial nanoparticles for intravitreous
drug delivery has increased significantly. However, little is known about the effect of material properties on intravitreous
Principal Findings: To find the answer, nanoparticles made of hyaluronic acid (HA), poly (I-lactic acid) (PLLA), polystyrene
(PS), and Poly N-isopropyl acrylamide (PNIPAM) were tested using intravitreous rabbit implantation model. Shortly after
implantation, we found that most of the implants accumulated in the trabecular meshwork area followed by clearance from
the vitreous. Interestingly, substantial reduction of intraocular pressure (lOP) was observed in eyes implanted with particles
made of PS, PNIPAM and PLLA, but not HA nanoparticles and buffered salt solution control. On the other hand, based on
histology, we found that the particle implantation had no influence on cornea, iris and even retina. Surprisingly, substantial
CD11b+ inflammatory cells were found to accumulate in the trabecular meshwork area in some animals. In addition, there
was a good relationship between recruited CD11b+ cells and IOP reduction.
Conclusions: Overall, the results reveal the potential influence of nanoparticle material properties on IOP reduction and
inflammatory responses in trabecular meshwork. Such interactions may be critical for the development of future ocular
nanodevices with improved safety and perhaps efficacy.
Citation: Zou L, Nair A, Weng H, Tsai Y-T, Hu Z, et al. (2011) Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous
Implants. PLoS ONE 6(12): e28720. doi:10.1371/journal.pone.0028720
Editor: Mario A. Barbosa, Instituto de Engenharia Biomedica, University of Porto, Portugal
Received September 12, 2011; Accepted November 14, 2011; Published December 14, 2011
Copyright: 2011 Zou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by National Institutes of Health grant EB007271. The funder had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: Itang@uta.edu
Posterior ocular diseases, including glaucoma, macular degen-
eration, uveal melanoma and retinoblastoma are often hard to be
treated due to ocular tissue barriers [1-3]. While topical
administration is effective in the treatment of anterior chamber
diseases, it is ineffective in the treatment of diseases afflicting the
posterior segments of the eye . Major problems include washing
away of the drug by tears and the inefficient diffusion of drug from
the corneal side to the posterior [4,5]. Systemic injection does
deliver drugs to the posterior of the eye but is also associated with
non-specific accumulation of drug in other organs. In addition the
blood retinal barrier also hinders the diffusion of drug into the
posterior chamber . In light of this information, intraocular
drug injections have gained in importance. However, although
they achieve therapeutic drug levels, they are associated with high
vitreal clearance which necessitates multiple injections. This in
turn leads to complications of endophthalmitis and retinal
detachment [2,3,6]. There is a need for the development of
alternative treatments for posterior ocular diseases.
Many therapeutic strategies have been developed in recent
years. One such method is the use of biomaterial drug delivery
devices either in the form of implants or as micro or nanoparticles
[2,7,8]. Despite of their ability to release therapeutic agents for a
: PLoS ONE I www.plosone.org
prolonged period of time, ocular rod implants have been found to
be responsible for causing retinal detachment and endophthalmitis
. With the expansion of nanotechnology in medicine, a wide
variety of nanoparticle drug releasing devices have been fabricated
and tested for their ability to treat a wide range of diseases [1,9-
12]. Many studies have been done to explore the possibility of
using polymeric micro and nanoparticles for anterior and posterior
chamber drug delivery [1,9-15]. Although microparticles have
better drug loading capacity than nanoparticles, the latter is
recognized as favorable drug carrier due to its low risk on
hampering normal vision [16,17]. Although different types of
nanoparticles have been investigated for their ability to target
different cells, tissues and to cure different ocular diseases [9-
12,14,15,18-22]. very limited studies have been done to
systematically evaluate the effect of material physical and chemical
properties on their ocular tissue and cell compatibility.
It is well established that the physical and chemical properties of
materials affect their cell and tissue compatibility [23-27]. We thus
assumed that nanoparticles made of different materials are likely to
cause different extents of acute tissue responses in the eye. To test
this hypothesis, nanoparticles made of different materials were
included in this study. Specifically, nanoparticles were made out of
degradable polymers like poly (1-lactic acid) (PLLA), hydrogels like
poly N-isopropyl acrylamide (PNIPAM), non-degradable materials
December 2011 1 Volume 6 1 Issue 12 1 e28720
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Zou, Ling; Nair, Ashwin; Weng, Hong; Tsai, Yi-Ting; Hu, Zhibing & Tang, Liping. Intraocular Pressure Changes: An Important Determinant of the Biocompatibility of Intravitreous Implants, article, December 14, 2011; [San Francisco, California]. (digital.library.unt.edu/ark:/67531/metadc288003/m1/1/: accessed January 15, 2019), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT College of Arts and Sciences.