期刊
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS
卷 36, 期 10, 页码 715-724出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/jop.2020.0078
关键词
PAMAM dendrimer; ocular toxicology; biocompatibility; nanotechnology; safety; drug delivery
资金
- National Key RD Program [2017YFC1104602]
- National Natural Science Foundation of China [81771984]
Purpose: The human eye is a sophisticated and sensitive sensory organ. Because of the existence of the blood-ocular barrier and corneal-scleral barrier, safe and efficient ocular drug delivery system is highly desired; yet, it remains an unsolved issue. Due to the unique structure and drug loading property, Poly(amidoamine) (PAMAM) has received much attention in the ocular drug delivery investigation. Herein, we evaluated the ocular cytotoxicity and biosafety of PAMAM dendrimers. Methods: The ocular cytotoxicity and biosafety of PAMAM dendrimers were evaluated by conducting in vitro and in vivo experiments on ocular systems. The in vitro effect of PAMAM dendrimer of different generations (G4.0, G5.0, and G6.0) and concentrations on ocular cell metabolism, apoptosis, and oxidative damage were quantitatively assessed. In vivo biosafety of PAMAM dendrimers were further investigated on intraocular tissue by ocular irritation and intravitreal injection approaches. Results: It is found that that the cytotoxicity of PAMAM was time and generation dependent. PAMAM at a concentration below 50 mu g/mL had minimal impact on the ocular tissue, whereas it caused apparent damage when above 50 mu g/mL in the investigated situation. Further, our in vivo results showed that higher concentration of dendrimer (100 mu g/mL) was associated with functional impairment demonstrated via optical coherence tomography and electroretinogram, although macroscopic structural changes were absent in fundus and histopathological studies. Overall, a higher concentration of PAMAM, such as above 50 mu g/mL, may cause ocular functional damage. Conclusion: The PAMAM at the concentrations lower than 50 mu g/mL showed good biocompatibility and biosafety in human ocular cells and tissues.
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