Lysine-Based C60-Fullerene Nanoconjugates for Monomethyl Fumarate Delivery: A Novel Nanomedicine for Brain Cancer Cells

被引：20
作者：
Kumar, Manish [1 ]
Sharma, Gajanand [2 ]
Kumar, Rajendra [3 ]
Singh, Bhupinder [2 ,3 ]
Katare, Om Prakash [2 ]
Raza, Kaisar [1 ]
机构：
[1] Cent Univ Rajasthan, Sch Chem Sci & Pharm, Dept Pharm, NH-8, Ajmer 305817, Rajasthan, India
[2] Panjab Univ, Univ Inst Pharmaceut Sci, UGC Ctr Adv Studies, Sect 14, Chandigarh 160014, India
[3] Panjab Univ, UGC Ctr Excellence Applicat Nanomat Nanoparticles, Chandigarh 160014, India
来源：
ACS BIOMATERIALS SCIENCE & ENGINEERING | 2018年 / 4卷 / 06期
关键词：
neuroblastoma; brain delivery; pharmacokinetics; Prato reaction; linker; prodrug; bioavailability; C-60 fullerene nanoconjugate; WALLED CARBON NANOTUBES; BLOOD-BRAIN; CELLULAR UPTAKE; PHARMACOKINETIC PROFILE; ANTICANCER ACTIVITY; TARGETED THERAPY; DRUG-DELIVERY; MITOMYCIN-C; IN-VIVO; FULLERENE;
D O I：
10.1021/acsbiomaterials.7b01031
中图分类号：
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号：
0805 ; 080501 ; 080502 ;
摘要：
In the present study, water-soluble lysine-based C-60-fullerene nanoconjugates (CF-LYS-TEG-MMF) were synthesized using a biodegradable linker for the better delivery of monomethyl fumarate (MMF) employing Prato reaction. CF-LYS-TEG-MMF resulted in enhanced cytotoxicity on neuroblastoma cells, meanwhile found to be substantially biocompatible to erythrocytes. The designed nanoconjugate exhibited a pH-based drug release pattern, minimizing the leaching of drug at plasma pH. However, the carrier offered maximum drug release at cancer cell pH, indicating huge promise in internalization of drug molecules at the site of target. The pharmacokinetics of MMF in rodents was significantly improved in terms of enhanced bioavailable drug fraction in the central compartment, reduced drug clearance, elevated plasma concentrations and prolonged biological residence of drug. Enhanced in vitro efficacy in SH-SYSY neuroblastoma cells, improved erythrocyte compatibility, high drug loading, and conducive pharmacokinetic profile by CF-LYS-TEG-MMF offers a huge promise in brain drug delivery, dose reduction, and dosage-regimen alteration for the management of brain tumors employing MMF.
引用
收藏
页码：2134 / 2142
页数：17
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