Design and evaluation of lipoprotein resembling curcumin-encapsulated protein-free nanostructured lipid carrier for brain targeting.
Many nanoparticle matrixes have been demonstrated to be efficient in brain targeting, but there are still certain limitations for them. To overcome the shortcomings of the existing nanoparticulate systems for brain-targeted delivery, a lipoprotein resembling protein-free nanostructured lipid carrier (PS80-NLC) loaded with curcumin was constructed and assessed for in vitro and in vivo performance. Firstly, single factor at a time approach was employed to investigate the effects of various formulation factors. Mean particle sizes of ≤100nm, high entrapment efficiency (EE, about 95%) and drug loading (DL, >3%) were obtained for the optimized formulations. In vitro release studies in the presence of plasma indicated stability of the formulation under physiological condition. Compared with NLC, PS80-NLC showed noticeably higher affinity for bEnd.3 cells (1.56 folds greater than NLC) but with lower uptake in macrophages. The brain coronal sections showed strong and widely distributed fluorescence intensity of PS80-NLC than that of NLC in the cortex. Ex vivo imaging studies further confirmed that PS80-NLC could effectively permeate BBB and preferentially accumulate in the brain (2.38 times greater than NLC). The considerable in vitro and in vivo performance of the safe and biocompatible PS80-NLC makes it a suitable option for further investigations in brain targeted drug delivery.
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Fanfei
F
Meng
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
Sajid
S
Asghar
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Yurui
Y
Xu
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Jianping
J
Wang
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Xin
X
Jin
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Zhilin
Z
Wang
Department of Clinical Laboratory, People's Hospital of Liaocheng, Liaocheng 252000, PR China.
Jing
J
Wang
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China.
Qineng
Q
Ping
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: zhoujianp60@163.com.
Jianping
J
Zhou
Department of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: cpuyanyuxiao@163.com.
Yanyu
Y
Xiao
D000818:Animals; D001921:Brain / Q000187:drug effects*; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry*; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D004337:Drug Carriers; D008055:Lipids; D008074:Lipoproteins; D003474:Curcumin
Brain targeting; Curcumin; Drug delivery; Lipoprotein; Protein-free nanostructured lipid carrier