Administering antipsychotic drugs using a nasal spray may raise bioavailability and lower side effects according to a study published in the Journal of Controlled Release.

Existing oral or injectable antipsychotic drugs tend to demonstrate low bioavailability, making long-term medication delivery a challenge. They also come with serious side effects.

Because it facilitates a direct path to the brain through the olfactory and/or trigeminal nerves, intranasal administration may improve delivery while minimizing side effects.


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The researchers developed a sprayable in situgelling hydrogel to deliver the antipsychotic peptide PAOPA. The intranasal spray uses carboxymethyl chitosan, a water-soluble and mucoadhesive polymer, as well as oxidized starch nanoparticles.

In vivo animal studies used age-matched male Sprague-Dawley rats. Rats received a 0.5 mg/kg dose of PAOPA. A total of 6ix groups were tested using various combinations of the drug with and without the hydrogel and with and without an MK-801 neuroprotective agent, which was used to induce schizophrenia-like behavior.

Tests on the rats suggest that the intranasal spray using the hydrogel solution enhances PAOPA delivery to the brain using a combination of 3 mechanisms: PAOPA diffusion out of the immobilized gel, across the nasal epithelium, and into the brain, which prolongs the release of PAOPA in the nose; SNP-mediated transport of PAOPA across the nasal epithelium and to the brain; and/or SNP-mediated transport of PAOPA across the nasal epithelium followed by PAOPA release from the epithelial cells following SNP endocytosis.

“Hydrogels loaded with 0.5 mg/kg PAOPA can enable full alleviation of induced schizophrenia symptoms in rats for up to 3 days (72 h), while a semi-quantitative nanoparticle distribution analysis indicated the presence of significant concentrations of SNPs in the brain over the same time period,” the researchers concluded.

“We fully expect that similar benefits could be achieved with other emerging antipsychotic peptides, offering the potential to enable effective and minimally invasive schizophrenia therapy while significantly reducing the burden of repeated administration that currently limits patient adherence to schizophrenia treatment regimens.”

Multiple authors are co-inventors on a provisional patent application based in part on work disclosed in the study.

Reference

Majcher MJ, Babar A, Lofts A, et al.  In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide. J Control Release. 2020 Dec 28;330:738-752. doi:10.1016/j.jconrel.2020.12.050