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考察布林佐胺凝胶纳米乳剂制剂的潜在眼毒性和治疗效果。

Investigating the ocular toxicity potential and therapeutic efficiency of gel nanoemulsion formulations of brinzolamide.

作者信息

Talaei Sima, Mahboobian Mohammad Mehdi, Mohammadi Mojdeh

机构信息

Department of Toxicology and Pharmacology, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Boulevard, Hamadan 6517838678, Iran.

Department of Pharmaceutics, School of Pharmacy, Hamadan University of Medical Sciences, Shahid Fahmideh Boulevard, Hamadan 6517838678, Iran.

出版信息

Toxicol Res (Camb). 2020 Aug 25;9(4):578-587. doi: 10.1093/toxres/tfaa066. eCollection 2020 Jul.

Abstract

Glaucoma is an ocular disease i.e. more common in older adults with elevated intraocular pressure and a serious threat to vision if it is not controlled. Due to the limitations regarding the conventional form of brinzolamide (Azopt®), two optimum formulations of gel nanoemulsion were developed. To ensure the safety and efficacy of developed formulations for ocular drug delivery, the current study was designed. MTT assay was carried out on the human retinal pigmentation epithelial cells. To investigate the irritation potential of the chosen formulations, hen's egg test-chorioallantoic membrane as a borderline test between and methods has been done. The modified Draize method was utilized to evaluate eye tolerance against the selected formulations. Intraocular pressure was measured by applying the prepared formulations to the eyes of normotensive albino rabbits in order to assess the therapeutic efficacy. Based on MTT test, cell viability for NE-2 at 0.1% and NE-1 at 0.1 and 0.5% concentrations was acceptable. The results of the hen's egg test-chorioallantoic membrane test indicated no sign of vessel injury on the chorioallantoic membrane surface for both formulations. Also, during 24 h, both formulations were well-tolerated by rabbit eyes. The pharmacodynamics effects of formulations had no difference or were even higher than that of suspension in case of adding lower concentration (0.5%) of brinzolamide to the formulations. With regard to the results of the mentioned methods, our advanced formulations were effective, safe, and well-tolerated, thus can be introduced as an appropriate vehicle for ocular delivery of brinzolamide.

摘要

青光眼是一种眼部疾病,在老年人中更为常见,眼压升高,若不加以控制,会对视力构成严重威胁。由于传统布林佐胺(Azopt®)剂型存在局限性,因此开发了两种最佳的凝胶纳米乳剂配方。为确保所开发的眼部给药制剂的安全性和有效性,设计了本研究。对人视网膜色素上皮细胞进行了MTT试验。为研究所选制剂的刺激潜力,已采用鸡胚绒毛尿囊膜试验作为介于[此处原文缺失相关内容]和[此处原文缺失相关内容]方法之间的一种边界试验。采用改良的Draize方法评估对所选制剂的眼耐受性。通过将制备的制剂应用于正常血压白化兔的眼睛来测量眼压,以评估其治疗效果。基于MTT试验,浓度为0.1%的NE - 2以及浓度为0.1%和0.5%的NE - 1的细胞活力是可接受的。鸡胚绒毛尿囊膜试验结果表明,两种制剂在绒毛尿囊膜表面均未出现血管损伤迹象。此外,在24小时内,两种制剂在兔眼中均耐受性良好。在制剂中添加较低浓度(0.5%)的布林佐胺时,制剂的药效学作用无差异,甚至高于混悬液。基于上述方法的结果,我们开发的制剂有效、安全且耐受性良好,因此可作为布林佐胺眼部给药的合适载体引入。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f33a/7467242/e731583f5c33/tfaa066ga.jpg

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