High-Density Lipoprotein Engineering for Eye-Drop Treatment of Age-Related Macular Degeneration

被引：3

作者：

Fukuda, Ryosuke ^{[1
]}

Mahmuda, Nargis ^{[1
,2
]}

Kasirawat, Sawangrat ^{[1
,3
]}

Kawakami, Ryo ^{[1
]}

Shima, Rumina ^{[1
]}

Mizukami, Yu ^{[1
]}

Shibukawa, Shiori ^{[1
]}

Tada, Yuki ^{[1
]}

Kawanishi, Fumitake ^{[1
]}

Ogura, Masatsune ^{[4
]}

Matsuki, Kota ^{[5
]}

Nagai, Yoshinori ^{[1
]}

Nakano, Eri ^{[6
]}

Suda, Kenji ^{[6
]}

Tsujikawa, Akitaka ^{[6
]}

Murakami, Tatsuya ^{[1
,7
]}

机构：

[1] Toyama Prefectural Univ, Grad Sch Engn, Dept Biotechnol & Pharmaceut Engn, Imizu, Toyama 9390398, Japan

[2] Dhaka Int Univ, Dept Pharm, Dhaka 1212, Bangladesh

[3] Chiang Mai Univ, Fac Pharm, Dept Pharmaceut Sci, Chiang Mai 50200, Thailand

[4] Chiba Univ, Grad Sch Med, Dept Gen Med Sci, Chiba, Chiba 2608677, Japan

[5] Hirosaki Univ, Grad Sch Med, Hirosaki, Aomori 0368562, Japan

[6] Kyoto Univ, Grad Sch Med, Sakyo Ku, Kyoto 6068507, Japan

[7] Kyoto Univ, Inst Integrated Cell Mat Sci iCeMS, Sakyo Ku, Kyoto 6068501, Japan

来源：

ADVANCED THERAPEUTICS | 2023年 / 6卷 / 11期

关键词：

absorption enhancer; age-related macular degeneration; antiangiogenic activity; anti-inflammatory activity; high-density lipoproteins; neovasculature-targeting; TUMOR-ASSOCIATED MACROPHAGES; BREAST-CANCER METASTASIS; IMMUNOGENIC CELL-DEATH; TYROSINE KINASE INHIBITOR; CD4(+) T-CELLS; ANLOTINIB; CHOLESTEROL; IMMUNOMETABOLISM; SUPPRESSION; PROGRESSION;

D O I：

10.1002/adtp.202300186

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Eye-drop treatments of age-related macular degeneration (AMD) are desirable; however, no clinically approved eye drop has been reported to date. This study aim to evaluate the therapeutic activity of eye-drop instillation of a high-density lipoprotein (HDL) variant bearing a cell-penetrating peptide and neovasculature-targeted peptide (AsnGlyArg [NGR] peptide) in a mouse model at a dose of 0.6-0.85 mu g protein/eye drop. The results reveal that the activity of the abovementioned variant was >10-fold higher than that of the previous variant lacking an NGR peptide. In addition, the anti-inflammatory activity, cholesterol-efflux capacity, and antiangiogenic activity of reconstituted HDL are significantly augmented by the attachment of these two peptides. The mechanism underlying this dramatic improvement is likely the expression of CD13, an NGR peptide receptor, on the cornea and conjunctiva in mice. CD13 mRNA/protein expression is also detected in cultured human corneal and conjunctival cells. These results demonstrate that NGR peptide is an unprecedented class of an absorption enhancer on the eye surface. Thus, HDL engineering is a potential strategy for developing eye drops to treat neovascular AMD by enhancing the ocular surface absorption and HDL functionalities.

引用

页数：11

共 29 条

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