The proton permeability of self-assembled polymersomes and their neuroprotection by enhancing a neuroprotective peptide across the blood-brain barrier after modification with lactoferrin.
Yu. Yuan Y; Jiang. Xinguo X; Gong. Shuyu S; Feng. Liang L; Zhong. Yanqiang Y; Pang. Zhiqing Z
Key Findings
- Polymersomes are far more stable and less leaky than regular liposomes
- Adding about 101 lactoferrin molecules per polymersome gives the best brain‑crossing ability
- Lactoferrin‑modified polymersomes loaded with S14G‑humanin protect rats from amyloid‑induced learning and memory deficits
Practical Outcomes
- For now, the takeaway is that simply taking humanin supplements won’t reach the brain effectively. Future therapies may use similar nanocarriers to get humanin into the CNS, but you’ll need to wait for commercial products or clinical trials before applying this.
Summary
Scientists built tiny, stable particles called polymersomes and coated them with a protein (lactoferrin) so they can slip across the brain’s protective barrier. When they loaded these particles with a modified version of the peptide humanin, they got it into mouse brains and saw protection against memory loss caused by an Alzheimer‑like toxin. The study shows a promising way to deliver humanin to the brain, but the method isn’t something you can do at home yet.
Abstract
Biotherapeutics such as peptides possess strong potential for the treatment of intractable neurological disorders. However, because of their low stability and the impermeability of the blood-brain barrier (BBB), biotherapeutics are difficult to transport into brain parenchyma via intravenous injection. Herein, we present a novel poly(ethylene glycol)-poly(d,l-lactic-co-glycolic acid) polymersome-based nanomedicine with self-assembled bilayers, which was functionalized with lactoferrin (Lf-POS) to facilitate the transport of a neuroprotective peptide into the brain. The apparent diffusion coefficient (D*) of H(+) through the polymersome membrane was 5.659 × 10(-26) cm(2) s(-1), while that of liposomes was 1.017 × 10(-24) cm(2) s(-1). The stability of the polymersome membrane was much higher than that of liposomes. The uptake of polymersomes by mouse brain capillary endothelial cells proved that the optimal density of lactoferrin was 101 molecules per polymersome. Fluorescence imaging indicated that Lf101-POS was effectively transferred into the brain. In pharmacokinetics, compared with transferrin-modified polymersomes and cationic bovine serum albumin-modified polymersomes, Lf-POS obtained the greatest BBB permeability surface area and percentage of injected dose per gram (%ID per g). Furthermore, Lf-POS holding S14G-humanin protected against learning and memory impairment induced by amyloid-β25-35 in rats. Western blotting revealed that the nanomedicine provided neuroprotection against over-expression of apoptotic proteins exhibiting neurofibrillary tangle pathology in neurons. The results indicated that polymersomes can be exploited as a promising non-invasive nanomedicine capable of mediating peptide therapeutic delivery and controlling the release of drugs to the central nervous system.
Study Information
pubmed
2014
2014-02-07T00:00:00.000Z
10.1039/c3nr05196j
41
35