Amphiphilic Copolymers Shuttle Drugs Across the Blood–Brain Barrier

Abstract

Medical treatment of diseases of the central nervous system requires transport of drugs across the blood-brain barrier (BBB). Here, it is extended previously in vitro experiments with a model compound to show that the non-water-soluble and brain-impermeable drug domperidone (DOM) itself can be enriched in the brain by use of an amphiphilic copolymer as a carrier. This carrier consists of poly(N-(2-hydroxypropyl)-methacrylamide), statistically copolymerized with 10 mol% hydrophobic lauryl methacrylate, into whose micellar aggregates DOM is noncovalently absorbed. As tested in a BBB model efficient transport of DOM across, the BBB is achievable over a wide range of formulations, containing 0.8 to 35.5 wt% domperidone per copolymer. In neither case, the polymer itself is translocated across the BBB model. In vivo experiments in mice show that already 10 min after intraperitoneal injection of the polymer/domperidone (PolyDOM) formulation, domperidone can be detected in blood and in the brain. Highest serum and brain levels of domperidone are detected 40 min after injection. At that time point serum domperidone is increased 48-fold. Most importantly, domperidone is exclusively detectable in high amounts in the brain of PolyDOM injected mice and not in mice injected with bare domperidone.

In VitroBlood–Brain Barrier Permeability and Cytotoxicity of an Atorvastatin-Loaded Nanoformulation Against Glioblastoma in 2D and 3D Models

“…[45][46][47][48] In addition, Zentel and co-workers could show that also am-phiphilic copolymers based on 2-hydropropylacrylamide and laurylacrylate could increase transport of small molecules across the BBB in vitro and in vivo. [49][50][51]…”

“…It is important to note that bothcoated and uncoated nanoparticleswere able to penetrate the BBB in vivo , reaching the maximum brain concentration 1 h postintravenous injection. Pioneering work by Kabanov and co-workers revealed that several amphiphilic polymers can facilitate the transport of small molecules and proteins across the BBB. − In addition, Zentel and co-workers could show that also amphiphilic copolymers based on 2-hydropropylacrylamide and laurylacrylate could increase the transport of small molecules across the BBB in vitro and in vivo . − …”

Efficient Cholera Toxin B Subunit‐Based Nanoparticles with MRI Capability for Drug Delivery to the Brain Following Intranasal Administration

“…Due to the limitation of the blood–brain barrier (BBB), medicine cannot be effectively sent to the expected diseased region . As previously reported, the efficiency of drug delivery to the brain has been shown to be reduced to less than 5% . This intractable disease requires a traceable and effective delivery system.…”

Labeling of DOTA-conjugated HPMA-based polymers with trivalent metallic radionuclides for molecular imaging

“…Interestingly, our findings on the different blood components suggested that the homopolymer interacts with serum proteins and with blood cells. Former studies of our group showed that HPMA- ran -LMA copolymers interact with very low density lipoproteins in the blood [ 42 ] and with cell membranes [ 43 , 44 ]. Not only structure and size of the polymer but furthermore the cell type is crucial for polymer delivery.…”