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用于眼部给药的脂质体舒尼替尼:脉络膜新生血管形成的潜在治疗方法。

Liposomal sunitinib for ocular drug delivery: A potential treatment for choroidal neovascularization.

作者信息

Tavakoli Shirin, Puranen Jooseppi, Bahrpeyma Sina, Lautala Veera E, Karumo Suvi, Lajunen Tatu, Del Amo Eva M, Ruponen Marika, Urtti Arto

机构信息

Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00790 University of Helsinki, Finland.

School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Yliopistonranta 1, 70210 Kuopio, Finland.

出版信息

Int J Pharm. 2022 May 25;620:121725. doi: 10.1016/j.ijpharm.2022.121725. Epub 2022 Apr 8.

Abstract

Choroidal neovascularization (CNV) is a prevalent vision-threatening vascular disorder in aging population. CNV is associated with several diseases in the posterior segment of the eye such as age-related macular degeneration (AMD). In this study we developed sunitinib-loaded liposomes to block the neovascularization signalling pathway through inhibition of tyrosine kinase of vascular endothelial growth factor receptors (VEGFRs). Liposomal sunitinib formulations were prepared by thin film hydration method and studied for their encapsulation efficiency (EE), loading capacity (LC) and drug release profile in buffer andvitreous. Our finding showed that the liposomes (mean size 104 nm) could effectively entrap sunitinib (EE ≈ 95%) at relatively high loading capacity (LC ≈ 5%) and release sunitinib over at least 3 days. Intravitreal sunitinib-loaded liposomes revealed inhibitory effect on established neovascularization in laser-induced CNV mouse model while the intravitreal injection of sunitinib solubilized with cyclodextrin was inefficient in management of neovascularization. Accordingly, liposomal sunitinib is a promising drug delivery system that should be further studied to inhibit the CNV related to AMD.

摘要

脉络膜新生血管(CNV)是老年人群中一种常见的威胁视力的血管疾病。CNV与眼部后段的多种疾病相关,如年龄相关性黄斑变性(AMD)。在本研究中,我们制备了载有舒尼替尼的脂质体,通过抑制血管内皮生长因子受体(VEGFRs)的酪氨酸激酶来阻断新生血管信号通路。采用薄膜水化法制备脂质体舒尼替尼制剂,并研究其包封率(EE)、载药量(LC)以及在缓冲液和玻璃体内的药物释放曲线。我们的研究结果表明,脂质体(平均粒径104 nm)能够以相对较高的载药量(LC≈5%)有效地包封舒尼替尼(EE≈95%),并在至少3天内释放舒尼替尼。玻璃体内注射载有舒尼替尼的脂质体对激光诱导的CNV小鼠模型中已形成的新生血管有抑制作用,而玻璃体内注射用环糊精增溶的舒尼替尼对新生血管的治疗效果不佳。因此,脂质体舒尼替尼是一种有前景的药物递送系统,应进一步研究以抑制与AMD相关的CNV。

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