Subconjunctival Delivery of Sorafenib-Tosylate-Loaded Cubosomes for Facilitated Diabetic Retinopathy Treatment: Formulation Development, Evaluation, Pharmacokinetic and Pharmacodynamic (PKPD) Studies

被引：2

作者：

Madhusudhan, Sharadha ^{[1
]}

Gupta, Naresh Vishal ^{[1
]}

Rahamathulla, Mohamed ^{[2
]}

Chidambaram, Saravana Babu ^{[3
,4
]}

Osmani, Riyaz Ali M. ^{[1
]}

Ghazwani, Mohammed ^{[2
,5
]}

Ahmed, Mohammed Muqtader ^{[6
]}

Farhana, Syeda Ayesha ^{[7
]}

Sarhan, Mohammed Y. ^{[8
]}

Tousif, Ahmed Hediyal ^{[3
,4
]}

机构：

[1] JSS Acad Higher Educ Res, JSS Coll Pharm, Dept Pharmaceut, Mysuru 570015, Karnataka, India

[2] King Khalid Univ, Coll Pharm, Dept Pharmaceut, Abha 62529, Saudi Arabia

[3] JSS Acad Higher Educ & Res, JSS Coll Pharm, Dept Pharmacol, Mysuru 570015, Karnataka, India

[4] JSS Acad Higher Educ & Res, Ctr Expt Pharmacol & Res, Cent Anim Facil, Toxicol, Mysuru 570015, Karnataka, India

[5] King Khalid Univ, Canc Res Unit, Abha 62529, Saudi Arabia

[6] Prince Sattam Bin Abdul Aziz Univ, Coll Pharm, Dept Pharmaceut, Al Kharj 11942, Saudi Arabia

[7] Qassim Univ, Unaizah Coll Pharm, Dept Pharmaceut, Unaizah 51911, Saudi Arabia

[8] Hashemite Univ, Dept Special Surg, Zarqa 13133, Jordan

来源：

PHARMACEUTICS | 2023年 / 15卷 / 10期

关键词：

diabetic retinopathy; cubosome nanocarriers; sorafenib tosylate; subconjunctival injection; VEGF; ENDOTHELIAL GROWTH-FACTOR; OPHTHALMIC DELIVERY; NANOPARTICLES; SYSTEM; OPTIMIZATION; PERMEATION; INHIBITORS; SAFETY; VEGF;

D O I：

10.3390/pharmaceutics15102419

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Diabetic retinopathy (DR) is a microvascular complication associated with vascular endothelial growth factor (VEGF) overexpression. Therapeutic delivery to the retina is a challenging phenomenon due to ocular biological barriers. Sorafenib tosylate (ST) is a lipophilic drug with low molecular weight, making it ineffective at bypassing the blood-retinal barrier (BRB) to reach the target site. Cubosomes are potential nanocarriers for encapsulating and releasing such drugs in a sustained manner. The present research aimed to compare the effects of sorafenib-tosylate-loaded cubosome nanocarriers (ST-CUBs) and a sorafenib tosylate suspension (ST-Suspension) via subconjunctival route in an experimental DR model. In this research, ST-CUBs were prepared using the melt dispersion emulsification technique. The distribution of prepared nanoparticles into the posterior eye segments was studied with confocal microscopy. The ST-CUBs were introduced into rats' left eye via subconjunctival injection (SCJ) and compared with ST-Suspension to estimate the single-dose pharmacokinetic profile. Streptozotocin (STZ)-induced diabetic albino rats were treated with ST-CUBs and ST-Suspension through the SCJ route once a week for 28 days to measure the inhibitory effect of ST on the diabetic retina using histopathology and immunohistochemistry (IHC) examinations. Confocal microscopy and pharmacokinetic studies showed an improved concentration of ST from ST-CUBs in the retina. In the DR model, ST-CUB treatment using the SCJ route exhibited decreased expression levels of VEGF, pro-inflammatory cytokines, and adhesion molecules compared to ST-Suspension. From the noted research findings, it was concluded that the CUBs potentially enhanced the ST bioavailability. The study outcomes established that the developed nanocarriers were ideal for delivering the ST-CUBs via the SCJ route to target the retina for facilitated DR management.

引用

页数：23