Pluronic F127 and D-\u03b1-Tocopheryl Polyethylene Glycol Succinate (TPGS) Mixed Micelles for Targeting Drug Delivery across The Blood Brain Barrier

Xin Meng,Xiaotong Lu,Teng Shen,Jiajia Li,Jiansheng Liu,Xiangrong Yu

doi:10.1038/s41598-017-03123-y

Abstract

A novel polymeric mixed micelle composed of Pluronic F127 and D-α-tocopheryl polyethylene glycol succinate (TPGS) was developed to improve the delivery of fluorescent dyes and protein across the blood brain barrier (BBB). Rhodamine 123 (Rho123) and DiR loaded mixed micelles, composed of Pluronic F127 and TPGS with proportion of 4:1 (FT), were prepared by thin-film hydration, and β-galactosidase (β-Gal) loaded FT mixed micelles were prepared by self-assembly. The brain-targeted capability of FT mixed micelles were evaluated both in vitro and in vivo. The FT mixed micelles showed that a average particle size of 20.03 nm, and a low CMC of 0.0031% in water. The in vitro release of Rho123 from Rho123 loaded FT mixed micelles (FT/Rho123) presented a sustained-release property. FT/Rho123 also showed higher efficiency for the accumulation in brain capillary endothelial cells (BCECs) and brain tissues. β-Gal, a model protein, was also delivered and accumulated efficiently in the brain by spontaneous loading in the FT mixed micelles. Therefore, the results indicated that F127/TPGS mixed micelles may be considered as an effective nanocarrier for the brain-targeted delivery of diagnostic and therapeutic drugs.

Highlights

Delivery systems which make the full use of the properties of nanomaterials while not fundamentally modifying the molecular structure of them[9]
Pluronic block copolymers consist of hydrophilic polyethylene oxide (PEO) and hydrophobic poly propylene oxide (PPO) segments arranged in a basic tri-block structure: PEO-PPO-PEO, which were widely used as micellar carriers[6, 14]
We propose that Pluronic F127 and tocopheryl polyethylene glycol succinate (TPGS) could be used for preparing mixed micellar carriers, which may combine the effects of two biomaterials and enhance the drug transport across the blood brain barrier (BBB)

Summary

Introduction

Delivery systems which make the full use of the properties of nanomaterials while not fundamentally modifying the molecular structure of them (e.g. self-assembly)[9]. Pluronic block copolymers consist of hydrophilic polyethylene oxide (PEO) and hydrophobic poly propylene oxide (PPO) segments arranged in a basic tri-block structure: PEO-PPO-PEO, which were widely used as micellar carriers[6, 14] Besides their ability to self-assemble into micelles, Pluronic block copolymers such as Pluronic P85, L61, P123 have been shown to be able to inhibit multidrug transporters, e.g., P-glycoprotein (P-gp), for increasing the delivery of agents to the brain[15, 16]. The in vitro and in vivo brain targeting capability of FT mixed micelles loading with fluorescent probe Rho[123] were assessed using brain capillary endothelial cells (BCECs) and normal rats respectively Both small-molecule fluorescent probe Rho[123] and macromolecular model protein drug β-Gal, were used to evaluate the brain targeting ability of F127/TPGS mixed micelle-based nanocarriers

Results

Discussion

Conclusion