Nanotechnology-based strategies for treatment of ocular disease

Abstract

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops, injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new, highly effective and important ocular nanomedicines.

Keywords: Diagnosis; Eye; Nanocarrier; Nanosystems; Ocular disease; Ocular drug delivery; Therapy.

Graphical abstract

Figure 1

Ocular anatomy and administration routes of both traditional drugs and nanosystems: the black arrows show different eye structures and the red arrows show various administration routes.

Figure 2

Schematic illustration of different nanotechnology-based ocular delivery systems.

Figure 3

A fabricated nanowafer can improve the corneal wound healing in a mouse cornea burn model. (A) Fluorescence images of mouse corneal surface; (B) Quantitative analysis of corneal surface healing. (Reproduced with permission from ACS artcile (direct link: http://pubs.acs.org/doi/full/10.1021/nn506599f).

Figure 4

Fluorescence images of bovine cornea with removed epithelium after exposed to silica nanoparticles of 0.5 h (A) and 1 h (B). The nanoparticles had a consistent size distribution and were functioned by thiolated groups and PEGylated 5000 Da, respectively. Reproduced with permission from ACS article. (direct link: http://pubs.acs.org/doi/full/10.1021/mp500332m).

Figure 5

(A) Schematic illustration of a multifunctional nanoparticle modified with a nuclear localization signaling peptide (NLS) and cell permeable peptide (TAT) to deliver gene to the posterior segment of the eye for blinding eye disease treatment63. The strategy includes three functions: (1) A biocompatible lipid molecule was used to pack DNA along with another biocompatible protamine molecule together as a non-viral nanoparticle carrier; (2) The modified peptides have both cell penetrating and nuclei targeting functions thus leading to the gene delivery to eye cells; (3) DNA was used to carry target gene and promote the cell-specific gene expression. (B) A light-activated, in situ forming hydrogel system was designed to realize sustainable release of bevacizumab for age-related macular degeneration (CNV) therapy. Reproduced with permission from ACS articles (direct links: http://pubs.acs.org/doi/full/10.1021/nl502275s; http://pubs.acs.org/doi/abs/10.1021/mp300716t).

Figure 6

Comparison of the intraocular pressure (IOP) between a commercial eye drop (Xalatan) and latanoprost-loaded liposome in rabbit glaucoma model. The data showed that after a single subconjunctival injection of the liposome, the IOP reduced for up to 120 days and then further reduced over another 180 days after a second injection. The results were comparable to daily eye drop (Xalatan). Reproduced with permission from ACS article (direct link: http://pubs.acs.org/doi/abs/10.1021/nn4046024).