Nasal Spray Peptides: What the Research Reports on Intranasal Delivery

"Nasal spray peptides" is a phrase used loosely online, but in the published literature it maps onto a specific research field: intranasal delivery of peptides, proteins and peptide-carrying nanocarriers, studied mostly in animals and formulation laboratories, with a smaller number of clinical programmes. This page describes what those papers reported. It does not compare products, does not suggest a route of administration, and does not describe protocols. This page is for educational purposes only and is not medical advice; consult a licensed physician before making any health decision.

Why researchers studied the nasal route at all

The central rationale in the literature is anatomical. A 2025 review in MedComm described the nasal-brain drug delivery route, its mechanisms, and applications to central nervous system diseases, framing the olfactory and trigeminal nerve pathways as routes by which molecules applied to the nasal mucosa may reach the brain (https://pubmed.ncbi.nlm.nih.gov/40487748/). A 2018 review in the Journal of Controlled Release examined nose-to-brain drug delivery with an update on clinical challenges and progress towards approval of anti-Alzheimer drugs, and researchers there focused on the gap between promising preclinical delivery data and regulatory approval (https://pubmed.ncbi.nlm.nih.gov/29772289/).

The interest is not peptide-specific in origin. Peptides are large, polar and enzymatically fragile, which is the same set of properties that limits their passage across the blood-brain barrier. A 2019 Biomaterials review catalogued nanomaterial-based blood-brain-barrier crossing strategies, describing the engineering approaches investigators have used to move payloads into the central nervous system (https://pubmed.ncbi.nlm.nih.gov/31546096/). Earlier, a 2014 ACS Nano review of precision nanomedicine in neurodegenerative diseases surveyed how nanoscale carriers were being applied to neurodegenerative targets (https://pubmed.ncbi.nlm.nih.gov/24660817/). Intranasal administration appears in this body of work as one delivery strategy among several, not as a settled solution.

Peptides and peptide-related agents with published intranasal research

The table below lists compounds and constructs for which intranasal work has been published in the papers cited on this page. It is a map of where literature exists, not a comparison of effectiveness.

Insulin as the most-studied intranasal peptide

Insulin is the peptide with the longest intranasal research record, and formulation science has repeatedly returned to it. A 2021 study in Biotechnology and Applied Biochemistry reported the synthesis and characterisation of a thermosensitive hydrogel based on quaternized chitosan designed for intranasal delivery of insulin, in which the researchers characterised the carrier system rather than treating patients (https://pubmed.ncbi.nlm.nih.gov/32250466/). Work of this kind illustrates a recurring theme: much of the intranasal peptide literature is about the vehicle — gels, micelles, nanoparticles, mucoadhesives — rather than about the peptide alone in saline.

GHK

GHK is frequently discussed in relation to skin and copper binding, but a 2023 bioRxiv preprint reported that intranasal GHK peptide enhanced resilience to cognitive decline in aging mice (https://pubmed.ncbi.nlm.nih.gov/38014118/). Two caveats belong in the same breath: that report was a preprint, meaning it had not completed journal peer review at the time of posting, and the study was conducted in mice, not humans (https://pubmed.ncbi.nlm.nih.gov/38014118/).

Peptide vaccines and mucosal immunity

A second cluster of intranasal peptide research sits in immunology, where the nasal mucosa is of interest as an immune induction site rather than as a shortcut to the brain. A 2025 Advanced Materials study reported that intranasal and intravenous sequential administration of survivin peptide–CpG nanovaccines elicited potent immunity toward glioblastoma (https://pubmed.ncbi.nlm.nih.gov/40489066/). In parallel, a 2025 ACS Nano study examined intranasal delivery of HPV therapeutic vaccines for enhanced mucosal immunisation and anti-tumour immunity (https://pubmed.ncbi.nlm.nih.gov/40794451/). These are oncology-directed immunology programmes in research models, and the peptides involved are antigens, not general-purpose "wellness" compounds.

Neuro-targeted peptides and carriers

Some neuroactive peptides appear in the literature without the intranasal route being the study's subject. A 2019 Translational Psychiatry paper reported on the autism/neuroprotection-linked ADNP and the NAP peptide regulating the excitatory glutamatergic synapse (https://pubmed.ncbi.nlm.nih.gov/30664622/). That paper is mechanistic, and it is worth separating mechanism papers from delivery papers when reading claims about "nasal peptides" online.

Carrier-focused neuro work has moved quickly. A 2025 International Journal of Pharmaceutics study described intranasal delivery of rapamycin via brain-targeting polymeric micelles for Alzheimer's disease treatment in a preclinical setting (https://pubmed.ncbi.nlm.nih.gov/40780467/), and a 2026 study in Small reported engineered biomimetic nanorobots orchestrating targeted nose-to-brain delivery to resolve neuron–glia entanglement against Parkinson's disease (https://pubmed.ncbi.nlm.nih.gov/41607240/). A 2026 Nature Biotechnology paper described self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins, addressing the separate problem of getting a macromolecule inside a cell once it has arrived (https://pubmed.ncbi.nlm.nih.gov/40374955/).

What delivery and bioavailability studies actually measured

Readers looking for a single "intranasal bioavailability percentage" for peptides will not find one in this literature, because the reported figures depend on the molecule, the formulation, the species and the sampling method. What the reviews describe instead are the variables that determine whether anything crosses at all. The 2025 MedComm review set out mechanisms of the nasal-brain route and its applications to central nervous system diseases, organising the field around those transport pathways (https://pubmed.ncbi.nlm.nih.gov/40487748/). Recurring formulation variables in the cited work include:

• Residence time on the mucosa — the rationale behind thermosensitive and mucoadhesive systems such as the quaternized chitosan hydrogel characterised for intranasal insulin (https://pubmed.ncbi.nlm.nih.gov/32250466/).
• Carrier design for brain targeting — polymeric micelles engineered for nose-to-brain transport of a payload (https://pubmed.ncbi.nlm.nih.gov/40780467/) and biomimetic nanorobots designed for targeted nose-to-brain delivery (https://pubmed.ncbi.nlm.nih.gov/41607240/).
• Intracellular release — self-assembling protein nanoparticles reported for cytosolic delivery of nucleic acids and proteins (https://pubmed.ncbi.nlm.nih.gov/40374955/).
• Barrier strategy generally — the nanomaterial-based blood-brain-barrier crossing strategies reviewed in 2019 (https://pubmed.ncbi.nlm.nih.gov/31546096/).

How intranasal compared with other routes in the published work

The literature rarely treats intranasal delivery as a straight substitute for injection. The clearest example of routes being studied together is the 2025 glioblastoma nanovaccine work, in which researchers reported intranasal and intravenous sequential administration of survivin peptide–CpG nanovaccines rather than intranasal alone (https://pubmed.ncbi.nlm.nih.gov/40489066/). In immunology, the argument for the nasal route is the mucosal compartment itself, as in the intranasal HPV therapeutic vaccine study aimed at enhanced mucosal immunisation and anti-tumour immunity (https://pubmed.ncbi.nlm.nih.gov/40794451/). In CNS work, the argument is access, with the 2018 review discussing nose-to-brain delivery specifically in the context of clinical challenges and progress towards approval of anti-Alzheimer drugs (https://pubmed.ncbi.nlm.nih.gov/29772289/).

In other words, the published comparison is contextual: the route was selected in each study for a mechanistic reason tied to that target. None of the cited papers positioned intranasal administration as a general-purpose replacement for systemic dosing of peptides, and none of them constitute guidance for individuals.

Tolerability and Adverse Events: What Studies Report

Most of the cited literature is preclinical or formulation-oriented, so human tolerability data are limited within this citation set. The 2018 Journal of Controlled Release review is the most directly relevant, since it addressed clinical challenges standing between nose-to-brain delivery and regulatory approval for anti-Alzheimer drugs (https://pubmed.ncbi.nlm.nih.gov/29772289/). The 2025 MedComm review similarly treated the nasal-brain route as a mechanism-driven field being translated toward central nervous system disease applications rather than a solved clinical technology (https://pubmed.ncbi.nlm.nih.gov/40487748/). Safety considerations raised across the nanocarrier literature — including the 2019 review of nanomaterial-based blood-brain-barrier crossing strategies (https://pubmed.ncbi.nlm.nih.gov/31546096/) and the 2014 review of precision nanomedicine in neurodegenerative diseases (https://pubmed.ncbi.nlm.nih.gov/24660817/) — relate to the carriers as much as to the peptides they carry. No specific adverse-event rates for intranasal peptide sprays in humans are stated here, because the verified papers cited on this page do not supply them.

Reading nasal peptide claims critically

Several features of this literature are easy to lose in summary:

1. Species matters. The GHK cognitive-resilience finding was reported in aging mice (https://pubmed.ncbi.nlm.nih.gov/38014118/), and rodent nasal anatomy differs substantially from human nasal anatomy.
2. Publication stage matters. That same GHK report was a preprint rather than a peer-reviewed journal article (https://pubmed.ncbi.nlm.nih.gov/38014118/).
3. The formulation is part of the finding. Results obtained with a quaternized chitosan thermosensitive hydrogel (https://pubmed.ncbi.nlm.nih.gov/32250466/) or with brain-targeting polymeric micelles (https://pubmed.ncbi.nlm.nih.gov/40780467/) describe those systems, not arbitrary nasal solutions.
4. Mechanism papers are not delivery papers. Work on ADNP/NAP and the excitatory glutamatergic synapse addressed synaptic regulation (https://pubmed.ncbi.nlm.nih.gov/30664622/).
5. Approval is a separate question. The 2018 review framed nose-to-brain delivery as still working toward approval in the Alzheimer's setting (https://pubmed.ncbi.nlm.nih.gov/29772289/).

Regulatory context

Many peptides discussed under the "nasal spray" heading online are supplied for research use only and are not approved drug products; a research-use-only designation means a material has not been evaluated for human administration. Approved intranasal medicines exist in other drug classes and are regulated as finished pharmaceutical products with defined labelling. The research literature summarised above sits upstream of that process — the 2018 review explicitly addressed progress toward approval rather than approved status (https://pubmed.ncbi.nlm.nih.gov/29772289/). This page is educational and is not legal or medical advice.

References

• The Nasal-Brain Drug Delivery Route: Mechanisms and Applications to Central Nervous System Diseases (MedComm, 2025)
• Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs (Journal of Controlled Release, 2018)
• Nanomaterial-based blood-brain-barrier (BBB) crossing strategies (Biomaterials, 2019)
• Precision nanomedicine in neurodegenerative diseases (ACS Nano, 2014)
• Synthesis and characterization of thermosensitive hydrogel based on quaternized chitosan for intranasal delivery of insulin (Biotechnology and Applied Biochemistry, 2021)
• Intranasal GHK peptide enhances resilience to cognitive decline in aging mice (bioRxiv, 2023)
• Intranasal and Intravenous Sequential Administration of Survivin Peptide-CpG Nanovaccines Elicits Potent Immunity Toward Glioblastoma (Advanced Materials, 2025)
• Intranasal Delivery of HPV Therapeutic Vaccines for Enhanced Mucosal Immunization and Anti-Tumor Immunity (ACS Nano, 2025)
• Intranasal delivery of rapamycin via brain-targeting polymeric micelles for Alzheimer's disease treatment (International Journal of Pharmaceutics, 2025)
• Engineered Biomimetic Nanorobots Orchestrate Targeted Nose-to-Brain Delivery to Resolve Neuron-Glia Entanglement against Parkinson's Disease (Small, 2026)
• Self-assembling protein nanoparticles for cytosolic delivery of nucleic acids and proteins (Nature Biotechnology, 2026)
• The autism/neuroprotection-linked ADNP/NAP regulate the excitatory glutamatergic synapse (Translational Psychiatry, 2019)