Ansari Mudassir, Gupta Chandan, Kulkarni Yogesh A, Singh Kavita
Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM's Narsee Monjee Institute of Management Studies (NMIMS) Deemed to be University, Mumbai, India.
Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, India.
Int J Pharm. 2025 Feb 25;671:125235. doi: 10.1016/j.ijpharm.2025.125235. Epub 2025 Jan 16.
The current research discusses polymer conjugation, formulation development, and evaluation of sorafenib-loaded polymeric nanomicelles of conjugated soluplus (solu-tin) and polymeric mixed nanomicelles of conjugated soluplus (solu-tin) with conjugated poloxamer 188 (polo-tin) for site-specific posterior segment delivery to the retina in managing retinoblastoma. Firstly, the soluplus and poloxamer 188 were conjugated with biotin by Fischer esterification reaction and evaluated by FTIR and H NMR for confirmation of covalent bond formation involving the carboxyl group of biotin and hydroxyl group of polymers. Secondly, the sorafenib-loaded solu-tin nanomicelles and mixed nanomicelles of solu-tin with polo-tin were formulated by the thin film hydration method. Thereafter, these nanomicelles were evaluated and displayed suitable outcomes for particle size (78.53 nm and 73.17 nm), PDI (0.089 and 0.074), zeta potential (-3.65 mV and -4.17 mv), entrapment efficiency (99.23 % and 99.83 %), in vitro drug release (4 h and 8 h), solid-state analysis, osmolality (290 mOsm/kg and 293 mOsm/kg), pH (7.4 and 7.4), TEM (spherical) and residual solvent analysis (287.90 ppm and 363.49 ppm). The ex vivo transcleral permeation at 8 h was found to be 548.45 ng/cm and 281.61 ng/cm, respectively. Both the drug-loaded nanomicelles displayed a dose-dependent anticancer effect on Y-79 cells at all time points i.e. 6, 12, 18, and 24 h, and were non-toxic to normal retinal pigmented epithelial cell line (ARPE-19) when incubated for 24 h. Furthermore, the formulations were non-irritant (HET-CAM) and stable for 6 months. Hence, the developed technology is safe and efficacious for targeting the retina in managing retinoblastoma.
当前的研究探讨了用于视网膜母细胞瘤治疗中向视网膜后段进行靶向递送的聚合物共轭、制剂开发以及载有索拉非尼的共轭苏鲁普拉斯（solu-tin）聚合物纳米胶束和共轭苏鲁普拉斯（solu-tin）与共轭泊洛沙姆188（polo-tin）的聚合物混合纳米胶束的评估。首先，通过费歇尔酯化反应将苏鲁普拉斯和泊洛沙姆188与生物素共轭，并通过傅里叶变换红外光谱（FTIR）和氢核磁共振（H NMR）进行评估，以确认涉及生物素羧基和聚合物羟基的共价键形成。其次，通过薄膜水化法制备了载有索拉非尼的solu-tin纳米胶束以及solu-tin与polo-tin的混合纳米胶束。此后，对这些纳米胶束进行了评估，结果显示其在粒径（78.53纳米和73.17纳米）、多分散指数（PDI，0.089和0.074）、zeta电位（-3.65毫伏和-4.17毫伏）、包封率（99.23%和99.83%）、体外药物释放（4小时和8小时）、固态分析、渗透压（290毫渗摩尔/千克和293毫渗摩尔/千克）、pH值（7.4和7.4）、透射电子显微镜（TEM，球形）以及残留溶剂分析（287.90 ppm和363.49 ppm）方面呈现出合适的结果。8小时时的离体经巩膜渗透分别为548.45纳克/平方厘米和281.61纳克/平方厘米。两种载药纳米胶束在所有时间点（即6小时、12小时、18小时和24小时）对Y-79细胞均表现出剂量依赖性抗癌作用，并且在孵育24小时时对正常视网膜色素上皮细胞系（ARPE-19）无毒。此外，这些制剂无刺激性（鸡胚绒毛尿囊膜试验）且在6个月内稳定。因此，所开发的技术在视网膜母细胞瘤治疗中靶向视网膜是安全有效的。
