Topical Solution for Retinal Delivery: Bevacizumab and Ranibizumab Eye Drops in Anti-Aggregation Formula (AAF) in Rabbits.

IF 3.5 3区医学 Q2 CHEMISTRY, MULTIDISCIPLINARY

Pharmaceutical Research Pub Date : 2024-06-01 Epub Date: 2024-06-05 DOI:10.1007/s11095-024-03721-2

Steven A Giannos, Edward R Kraft, Jonathan D Luisi, Mary E Schmitz-Brown, Valentina Reffatto, Kevin H Merkley, Praveena K Gupta

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引用次数: 0

Abstract

Purpose: Wet age-related macular degeneration (AMD) is a blinding retinal disease. Monthly intravitreal anti-VEGF antibody injections of bevacizumab (off-label) and ranibizumab (FDA approved) are the standard of care. Antibody aggregation may interfere with ocular absorption/distribution. This study assessed topical delivery of dilute antibodies to the posterior segment of rabbit eyes using a novel anti-aggregation formula (AAF).

Methods: Bevacizumab, or biosimilar ranibizumab was diluted to 5 mg/ml in AAF. All rabbits were dosed twice daily. Substudy 1 rabbits (bevacizumab, 100 µl eye drops): Group 1 (bevacizumab/AAF, n = 6); Group 2 (bevacizumab/PBS, n = 7) and Vehicle control (AAF, n = 1). Substudy 2 rabbits (ranibizumab biosimilar/AAF, 50 µl eye drops): (ranibizumab biosimilar/AAF, n = 8). At 14.5 days, serum was drawn from rabbits. Aqueous, vitreous and retina samples were recovered from eyes and placed into AAF aliquots. Tissue analyzed using AAF as diluent.

Results: Bevacizumab in AAF permeated/accumulated in rabbit aqueous, vitreous and retina 10 times more, than when diluted in PBS. AAF/0.1% hyaluronic acid eye drops, dosed twice daily, provided mean tissue concentrations (ng/g) in retina (29.50), aqueous (12.34), vitreous (3.46), and serum (0.28 ng/ml). Additionally, the highest concentration (ng/g) of ranibizumab biosimilar was present in the retina (18.0), followed by aqueous (7.82) and vitreous (1.47). Serum concentration was negligible (< 0.04 ng/ml). No irritation was observed throughout the studies.

Conclusions: Bevacizumab and ranibizumab, in an AAF diluent eye drop, can be delivered to the retina, by the twice daily dosing of a low concentration mAb formulation. This may prove to be an adjunct to intravitreal injections.

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用于视网膜传输的局部溶液：抗聚集配方（AAF）中的贝伐单抗和雷珠单抗滴眼液在兔子身上的应用。

目的：湿性老年性黄斑变性（AMD）是一种致盲性视网膜疾病。贝伐珠单抗（非标示）和雷尼单抗（美国食品及药物管理局批准）每月一次的玻璃体内抗血管内皮生长因子抗体注射是标准的治疗方法。抗体聚集可能会影响眼部吸收/分布。本研究评估了使用新型抗聚集配方（AAF）向兔眼后节局部递送稀释抗体的情况：方法：将贝伐珠单抗或生物类似物雷尼珠单抗在 AAF 中稀释至 5 毫克/毫升。所有兔子每天用药两次。子研究 1 兔子（贝伐珠单抗，100 µl 滴眼液）：第 1 组（贝伐单抗/AAF，n = 6）；第 2 组（贝伐单抗/PBS，n = 7）和药物对照组（AAF，n = 1）。子研究 2 兔子（ranibizumab 生物类似物/AAF，50 µl 滴眼液）：(雷尼珠单抗生物类似物/AAF，n = 8）。14.5 天后，抽取兔子血清。从眼睛中采集水样、玻璃体样和视网膜样，并将其放入 AAF 等分液中。使用 AAF 作为稀释剂对组织进行分析：结果：AAF中的贝伐珠单抗在兔水样、玻璃体和视网膜中的渗透/蓄积量是在PBS中稀释时的10倍。AAF/0.1%透明质酸滴眼液每天用药两次，视网膜（29.50）、水（12.34）、玻璃体（3.46）和血清（0.28 ng/ml）中的平均组织浓度（ng/g）。此外，视网膜中的雷尼珠单抗生物类似物浓度（纳克/克）最高（18.0），其次是水样（7.82）和玻璃体（1.47）。血清中的浓度可忽略不计（结论：贝伐珠单抗和雷尼单抗生物类似物在视网膜中的浓度为 18.0%：贝伐珠单抗和雷尼珠单抗在 AAF 稀释眼药水中，可通过每天两次给药的低浓度 mAb 制剂输送到视网膜。这可能被证明是玻璃体内注射的一种辅助方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmaceutical Research 医学-化学综合

CiteScore

6.60

自引率

5.40%

发文量

276

审稿时长

3.4 months

期刊介绍： Pharmaceutical Research, an official journal of the American Association of Pharmaceutical Scientists, is committed to publishing novel research that is mechanism-based, hypothesis-driven and addresses significant issues in drug discovery, development and regulation. Current areas of interest include, but are not limited to: -(pre)formulation engineering and processing- computational biopharmaceutics- drug delivery and targeting- molecular biopharmaceutics and drug disposition (including cellular and molecular pharmacology)- pharmacokinetics, pharmacodynamics and pharmacogenetics. Research may involve nonclinical and clinical studies, and utilize both in vitro and in vivo approaches. Studies on small drug molecules, pharmaceutical solid materials (including biomaterials, polymers and nanoparticles) biotechnology products (including genes, peptides, proteins and vaccines), and genetically engineered cells are welcome.