Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye

Cheng-Han Tsai; Le Ngoc Hoang; Chun Che Lin; Liang-Chen Pan; Chiao-Li Wu; I-Chan Lin; Peng-Yuan Wang; Ching-Li Tseng

doi:10.3390/pharmaceutics14061253

Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye

Pharmaceutics. 2022 Jun 13;14(6):1253. doi: 10.3390/pharmaceutics14061253.

Authors

Cheng-Han Tsai¹, Le Ngoc Hoang¹, Chun Che Lin², Liang-Chen Pan³, Chiao-Li Wu³, I-Chan Lin^{4

5}, Peng-Yuan Wang^{6

7}, Ching-Li Tseng^{1

7}

Affiliations

¹ Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 11031, Taiwan.
² Institute of Organic and Polymeric Materials and Research and Development Center for Smart Textile Technology, National Taipei University of Technology, Taipei 106344, Taiwan.
³ School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei 11031, Taiwan.
⁴ Department of Ophthalmology, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan.
⁵ Department of Ophthalmology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
⁶ Oujiang Laboratory, Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging, Wenzhou Medical University, Wenzhou 325000, China.
⁷ International Ph.D. Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan.

Abstract

Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH-) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH- NPs were 390.0 nm and -35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2-50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier.

Keywords: drug delivery; eyedrops; hyaluronic acid; nanoparticles; posterior eye; retina; subconjunctival injection; surface charges.

Abstract

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