L-type amino acid transporter 1 targeting self-assembly polyelectrolyte nanocomplex with enhanced nose to brain delivery of oxytocin.
Oxytocin just got a serious delivery upgrade. Researchers in China engineered a new nanocomplex targeting the L-type amino acid transporter 1 (LAT1) to shuttle oxytocin from nose to brain, bypassing the usual roadblocks of the blood-brain barrier. This could open new doors for peptide brain delivery, and the details are worth a look for anyone working with neuropeptides.
J Control Release
by Hu Y, Liu T, Zhang Y et al.
“L-type amino acid transporter 1 targeting self-assembly polyelectrolyte nanocomplex with enhanced nose to brain delivery of oxytocin. Hu Y(1), Liu T(1), Zhang Y(2), Ding M(2), Shi G(3), Su H(4), Guan J(5), Fan X(6). Author information: (1)Department of Otolaryngology Head and Neck Surgery, Shengjing Hospital of China Medical University, Shenyang, China. (2)Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China. (3)Department of Neurology, People's Hospital of China Medical University, Shenyang, China. (4)School of Pharmacy, China Pharmaceutical University, Nanjing, China. (5)School of Pharmacy, Shenyang Key Laboratory of Intelligent Mucosal Drug Delivery Systems, Shenyang Pharmaceutical University, Shenyang, China; Joint International Research Laboratory of Intelligent Drug Delivery Systems, Ministry of Education, China; Lunan Pharmaceutical Group Co., Ltd., Shandong, China. (6)Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: fanxy@sj-hospital.org. L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids (AA) across the blood-brain barrier (BBB), which plays a crucial role and is widely employed in brain drug delivery. Thus, in this study, tryptophan (Trp), leucine (Leu) and tyrosine (Tyr) were selected and various amino acid grafted chitosan (CTS) was first synthesized and characterized by Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectrum. Furthermore, oxytocin (OT) loaded polyelectrolyte complex (PEC) based on various amino acid grafted chitosan and chondroitin sulfate (CS) as well as OT loaded chitosan-chondroitin sulfate PEC was fabricated and optimized by particle size, zeta potential and encapsulation efficiency (EE%). The morphologies and OT conformation stability of different PEC formulations were investigated by transmission electron microscopy (TEM) and circular dichroism (CD) spectroscopy respectively. Moreover, to further reveal the superiority of amino acid grafted chitosan PECs on mucosal permeation and brain targeting via LAT1 transporter, the ex vivo permeation study, in vivo pharmacokinetics behavior as well as brain distribution of OT in different PECs were also carried out by intranasal administration. It was found that both chitosan-chondroitin sulfate and amino acid grafted chitosan-chondroitin sulfate PECs exhibited comparable particle size ranging from 180 to 210 nm with a positive charge. The PEC formulation presented a sustained release behavior compared to the OT solution and better nasal mucosal permeation was observed for amino acid grafted chitosan-chondroitin sulfate PECs. Both pharmacokinetics behavior and brain distribution results demonstrated that amino acid grafted chitsaon could significantly improve the OT absorption and brain accumulation in the order of Trp > Tyr > Leu, compared to naked chitosan-chondroitin sulfate PECs and OT solution. The behavioral and immunofluorescence results also revealed that amino acid grafted chitosan-chondroitin sulfate PECs exhibited a superior inhibitory effect on oxycodone (Oxy) addiction. In conclusion, amino acid grafted chitosan-chondroitin sulfate PECs could significantly promote brain drug transportation and could be a potential vehicle for protein or peptide delivery via nasal to brain pathway. Copyright © 2026 Elsevier B.V. All rights reserved. Conflict of interest statement: Declaration of competing interest The authors declare that there is no conflict of interest.”
The team started with chitosan—already popular for nasal delivery—then grafted it with different amino acids (tryptophan, tyrosine, leucine). They paired this with chondroitin sulfate to build self-assembling polyelectrolyte complexes, then loaded these with oxytocin. The goal: see if these nano-vehicles could use LAT1 to boost brain uptake.
Key findings:
Particle size stayed tight—180 to 210 nm—with a positive charge, good for nasal mucosa sticking power.
The amino acid-grafted versions beat plain chitosan at getting oxytocin across the nasal tissue.
Brain levels weren’t just a little higher—the tryptophan-grafted complex delivered more oxytocin to the brain than the other versions, or oxytocin solution alone.
Sustained release: the nanocomplexes didn’t dump their payload all at once, keeping oxytocin available over time.
Animal studies showed not just better brain penetration, but also behavioral effects—these formulations reduced oxycodone-seeking behavior.
For peptide researchers, this is big. Oxytocin’s classic delivery challenges aren’t unique—most research peptides struggle to cross the BBB. This LAT1-targeted nanocomplex could be a new platform for getting peptides where you want them, fast.
Interested in the specifics of oxytocin research? Check the oxytocin page for more background. Looking to optimize your own formulations or protocols? The research tools page is a good place to start.
End result: Targeted nanotechnology is making intranasal peptide delivery a lot more practical. This isn’t just theoretical—it’s moving the needle in real research labs.
Related Reading
Eu(3+)-mediated dual-crosslinked collagen-mimetic peptide/sodium alginate hydrogel for 3D-printed skin wound dressings.
News · Acta BiomaterAntimicrobial-potentiated colorectal cancer therapy with synchronized tumoricidal immunity via a self-deliverable nanopeptide.
News · J Am Pharm Assoc (2003)Real-world weight impact upon tirzepatide discontinuation at a single-center endocrinology clinic in patients with overweight or obesity.
For Research Use Only
All content published on Pushing Peptides is intended for educational and informational purposes only. The information provided is not intended as medical advice, diagnosis, or treatment. Peptides discussed in this article are research compounds and are not approved for human therapeutic use by the FDA or any other regulatory agency. All studies referenced involve animal models or in vitro research unless otherwise stated. Consult a qualified healthcare professional before making any decisions related to your health. Pushing Peptides does not sell peptides — we are a vendor directory and educational resource.