Mustard-inspired delivery shuttle for enhanced blood-brain barrier penetration and effective drug delivery in glioma therapy.

Abstract

Effective penetration through the blood-brain barrier (BBB) remains a challenge for the treatment of many brain diseases. In this study, a small molecule, sinapic acid (SA), extracted from mustard, was selected as a novel bioinspired BBB-permeable ligand for efficient drug delivery in glioma treatment. SA was conjugated on the surface of zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-encapsulated bovine serum albumin (BSA)-based nanoparticles, yielding nBSA-SA. The PMPC shell serves as a protective layer to prolong the in vivo blood circulation time with a better chance to cross the BBB. Furthermore, temozolomide (TMZ), which can be loaded onto the nanoparticles via electrostatic interactions with acrylic acid (AA) to generate AA-nBSA-SA-TMZ, was applied as an excellent chemotherapeutic drug for glioma therapy. The obtained nanoparticles with a distinct size show great BBB permeability. Through the mechanism study, it was found that the cell internalization of the SA-conjugated nanoparticles is an energy-dependent process with only transient disruption of the BBB. The biological evaluation results unambiguously suggest that drug-loaded nanoparticles can lead to strong apoptosis on the tumor site and increase the median survival time of glioma-bearing mice. Overall, this novel BBB-permeable ligand SA paves the way for the delivery of cargo into the brain and provides a powerful nanoplatform for glioma therapy via intravenous administration.

• Authors: Nan Wang, Pei Sun, Mingming Lv, Gangsheng Tong, Xin Jin, Xinyuan Zhu
• Journal: Biomaterials science (Biomater Sci) Vol. 5 Issue 5 Pg. 1041-1050 (May 02 2017) ISSN: 2047-4849 [Electronic] England
• PMID: 28378865 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Alkylating
• Coumaric Acids
• Drug Carriers
• Polymethacrylic Acids
• poly(2-methacryloyloxyethyl-phosphorylcholine)
• Phosphorylcholine
• Serum Albumin, Bovine
• sinapinic acid
• Dacarbazine
• Temozolomide

Topics

• Animals
• Antineoplastic Agents, Alkylating (administration & dosage, pharmacokinetics, therapeutic use)
• Biological Transport
• Blood-Brain Barrier (drug effects, metabolism)
• Brain Neoplasms (drug therapy, metabolism)
• Cattle
• Cell Line, Tumor
• Coumaric Acids (chemistry, metabolism)
• Dacarbazine (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
• Drug Carriers (chemistry, metabolism)
• Drug Delivery Systems
• Glioma (drug therapy, metabolism)
• Humans
• Mice
• Models, Molecular
• Mustard Plant (chemistry)
• Nanoparticles (chemistry, metabolism)
• Phosphorylcholine (analogs & derivatives, chemistry, metabolism)
• Polymethacrylic Acids (chemistry, metabolism)
• Rats
• Serum Albumin, Bovine (chemistry, metabolism)
• Temozolomide
• Tissue Distribution