A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-β₂₅₋₃₅-treated rats following intranasal administration.
Wu. Hongbing H; Li. Jianxu J; Zhang. Qizhi Q; Yan. Xiluan X; Guo. Liangran L; Gao. Xiaoling X; Qiu. Mingfeng M; Jiang. Xinguo X; Lai. Ren R; Chen. Hongzhuan H
Key Findings
- OL‑modified cubosomes increased brain uptake of the cargo 1.66‑ to 3.46‑fold versus unmodified cubosomes
- Intranasal delivery of S14G‑Humanin in OL‑cubosomes improved Morris water maze performance and lowered acetylcholinesterase activity in AD rats
- The OL coating remained biologically active and non‑immunogenic, enabling effective peptide delivery
Practical Outcomes
- For biohackers, the main takeaway is that intranasal delivery can enhance brain uptake of peptides like humanin, especially when paired with a carrier that improves nose‑to‑brain transport. The specific cubosome‑OL system is complex and not DIY‑ready, but the concept supports exploring nasal spray formulations of humanin or similar peptides, keeping in mind that current evidence is limited to animal studies.
Summary
Scientists created tiny, brain‑targeting particles called cubosomes and coated them with a small, non‑immune peptide (Odorranalectin) to help carry a humanin variant into the brain through the nose. In rats with Alzheimer‑like symptoms, this nose‑to‑brain delivery boosted brain levels of the peptide and improved memory test performance compared to regular particles.
Abstract
Because of the immunogenicity and toxicity in vivo of large molecules such as lectins, the application of these molecules is remarkably restricted in drug delivery systems. In this study, to improve the brain drug delivery and reduce the immunogenicity of traditional lectin modified delivery system, Odorranalectin (OL, 1700 Da), a novel non-immunogenic small peptide, was selected to establish an OL-modified cubosomes (Cubs) system. The streptavidin (SA)-conjugated Cubs were prepared by incorporating maleimide-PEG-oleate and taking advantage of its thiol group binding reactivity to conjugate with 2-iminothiolane thiolated SA; mono-biotinylated OL was then coupled with the SA-modified Cubs. The OL-decorated Cubs (OL-Cubs) devised via a non-covalent SA-biotin "bridge" made it easy to conjugate OL and determine the number of ligands on the surface of the Cubs using sensitive chemiluminescent detection. Retention of the bio-recognitive activity of OL after covalent coupling was verified by hemagglutination testing. Nose-to-brain delivery characteristic of OL-Cubs was investigated by in vivo fluorescent biodistribution using coumarin-6 as a marker. The relative uptake of coumarin carried by OL-Cubs was 1.66- to 3.46-fold in brain tissues compared to that incorporated in the Cubs. Besides, Gly14-Humanin (S14G-HN) as a model peptide drug was loaded into cubosomes and evaluated for its pharmacodynamics on Alzheimer's disease (AD) rats following intranasal administration by Morris water maze test and acetylcholinesterase activity determination. The results suggested that OL functionalization enhanced the therapeutic effects of S14G-HN-loaded cubosomes on AD. Thus, OL-Cubs might offer a novel effective and noninvasive system for brain drug delivery, especially for peptides and proteins.
Study Information
pubmed
2011
2011-10-28T00:00:00.000Z
10.1016/j.ejpb.2011.10.012
108
64