Korean J Ophthalmol.  2018 Oct;32(5):417-423. 10.3341/kjo.2017.0128.

Effective Delivery of Exogenous Compounds to the Optic Nerve by Intravitreal Injection of Liposome

• Lee J
• Goh U
• Park JH
• Park SW
• Heo H

• KMID: 2422072
• DOI: http://doi.org/10.3341/kjo.2017.0128

Abstract

PURPOSE
To improve the treatment efficiency of optic nerve diseases by delivering therapeutic materials to the optic nerve directly.
METHODS
We tried to optimize liposomal composition to deliver a payload to the optic nerve efficiently when it is injected intravitreally. After loading dexamethasone into this liposome, we tested the therapeutic effect of liposomes in this treatment using a murine model of ischemic optic neuropathy.
RESULTS
Our optimized liposome can deliver its payload to the optic nerve more efficiently than other tested compositions. Moreover, dexamethasone-loaded liposomes had a significant therapeutic effect in a murine model of ischemic optic neuropathy.
CONCLUSIONS
Here, we demonstrate the optimal composition of liposomes that could efficiently deliver intravitreally injected exogenous compounds to the optic nerve. We expect that the intravitreal injection of liposomes with the suggested composition would improve the delivery efficacy of therapeutic compounds to the optic nerve.

Keyword

Drug delivery; Liposomes; Optic nerve; Optic nerve diseases

MeSH Terms

Dexamethasone
Intravitreal Injections*
Liposomes*
Optic Nerve Diseases
Optic Nerve*
Optic Neuropathy, Ischemic
Dexamethasone
Liposomes

Figure

• 

  Fig. 1 Delivery of liposomes with various compositions to the optic nerve (ON) 72 hours after intravitreal injection. (A) DiI-LP-20 with 17.4 mV of surface charge showed the highest fluorescence signal at the ON. (B) Fluorescence quantification of intravitreally injected liposome at the ON. Liposomes were tagged with DiI (red) to image their distribution in the ON. Nuclei were stained with Hoechst (blue). GCL = ganglion cell layer; RPE = retinal pigment epithelium. Scale bar: 100 µm. Data represent average ± SD (n = 4, ***p < 0.001, one-way analysis of variance).

• 

  Fig. 2 Correlation between retinal distribution and optic nerve (ON) delivery of liposomal payloads (DiI). (A) Confocal microscopic images of the retina and ON. (B) Fluorescence quantification of intravitreally injected liposome at ganglion cell layer (GCL) and ON at each time point. Liposomes were tagged with DiI (red). Nuclei were stained with Hoechst (blue). RPE = retinal pigment epithelium. Scale bar: 100 µm. Data represent average ± SD (n = 4, *** p < 0.001, one-way analysis of variance).

• 

  Fig. 3 Therapeutic effsssect of dexamethasone-loaded liposome (Dex-liposome) on the murine non-arteritic ischemic optic neuropathy model. (A) Confocal microscopic images of the retina four weeks after intravitreal injection of phosphate buffered saline (PBS), free dexamethasone (Dex), liposome without payloads, and Dex-liposome. (B) Statistical analysis of retinal ganglion cell (RGC) number in each group. Nuclei were stained with Hoechst (blue). Scale bar: 100 µm. Data represent average ± SD (** p < 0.01, *** p < 0.001, one-way analysis of variance).

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