Mono-guanidine heterolipid based SMEDDS: A promising tool for cytosolic delivery of antineoplastics

被引：9

作者：

Shete, Harshad ^{[1
]}

Sable, Sandip ^{[1
]}

Tidke, Pritish ^{[2
]}

Selkar, Nilakash ^{[3
]}

Pawar, Yogita ^{[4
]}

Chakraborty, Avik ^{[4
]}

De, Abhijit ^{[2
]}

Vanage, Geeta ^{[3
]}

Patravale, Vandana ^{[1
]}

机构：

[1] Inst Chem Technol, Dept Pharmaceut Sci & Technol, Bombay 400019, Maharashtra, India

[2] Tata Mem Hosp, ACTREC, Mol Funct Imaging Lab, Navi Mumbai 410210, Maharashtra, India

[3] Natl Inst Res Reprod Hlth, Natl Ctr Preclin Reprod & Genet Toxicol, Bombay 400012, Maharashtra, India

[4] Tata Mem Ctr Annex, Radiat Med Ctr BARC, Bombay 400012, Maharashtra, India

来源：

BIOMATERIALS | 2015年 / 57卷

关键词：

Mono-guanidine heterolipid; Etoposide; Cationic SMEDDS; Intratumoral; Melanoma; IN-VITRO; CATIONIC LIPIDS; GENE DELIVERY; DRUG; SIRNA; FORMULATION; SYSTEMS; DESIGN; TUMOR; OIL;

D O I：

10.1016/j.biomaterials.2015.03.040

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

In the present work, we designed and synthesized a novel mono-guanidine heterolipid (MGH) and confirmed its structure by NMR and ESI-MS. The MGH was used as cationic lipid in developing etoposide loaded cationic self-microemulsifying drug delivery system (ECS) intended to be delivered by intratumoral route. The ECS exhibited size <50 nm and zeta potential +32.6 mV on dilution with various isotonic vehicles with no phase separation or drug precipitation. The ECS could be easily sterilized by membrane filtration method and showed excellent stability for 6 months. The ECS demonstrated excellent in vitro antiproliferative activity against B16F10 cells which is attributed to its high transfection efficiency and capability to cause prolonged drug release in cytosolic space. In vivo antitumor activity of ECS was conducted in B16F10 induced melanoma tumor model. ECS at 12 mg/kg dose showed superior tumor suppression ability and exhibited 100% survival compared to other formulations. Mice treated with ECS by intratumoral route, showed neither systemic side effect nor any evidences of hepatotoxicity and nephrotoxicity. In contrast, etoposide administered by intravenous route showed remarkable systemic toxicity, hepatotoxicity and nephrotoxicity. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：116 / 132

页数：17