In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide

Existing oral or injectable antipsychotic drug delivery strategies typically demonstrate low bioavailability to targeted brain regions, incentivizing the development of alternative delivery strategies. Delivery via the nasal cavity circumvents multiple barriers for reaching the brain but requires drug delivery vehicles with very specific properties to be effective.

Highlights

Bulk hydrogels made from SNPs and CMCh can be formed in situ within the rat nasal cavity.

Hydrogels are sprayable, hydrolytically-degradable, and mucoadhesive.

PAOPA-loaded hydrogels alleviate behavioural abnormalities in a pre-clinical model for at least 72h.

Behavioural abnormalities are alleviated at up to 75% lower drug dose versus conventional delivery.

Herein, we report in situ–gelling and degradable bulk nanoparticle network hydrogels consisting of oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) that enable intranasal delivery via spray, high nasal mucosal retention, and functional controlled release of the peptide drug PAOPA, a positive allosteric modulator of dopamine D2 receptor. PAOPA-loaded SNP-CMCh hydrogels can alleviate negative symptoms like behavioural abnormalities associated with schizophrenia (i.e. decreased social interaction time) for up to 72 h in an MK-801-induced pre-clinical rat model of schizophrenia at a low drug dosage (0.5 mg/kg); in comparison, conventional PAOPA administration via the intraperitoneal route requires twice the PAOPA dose to achieve a therapeutic effect that persists for only a few hours.

This strategy offers potential for substantially decreasing re-administration frequencies and overall drug doses (and thus side-effects) of a range of potential antipsychotic drugs via a minimally-invasive administration route.

Read the full article here

Article Information: Michael J. Majcher, Ali Babar, Andrew Lofts, Ashlyn Leung, Xiaoyun Li, Fahed Abu-Hijleh, Niels M.B. Smeets, Ram K. Mishra, Todd Hoare. Journal of Controlled Release, Volume 330, 2021, https://doi.org/10.1016/j.jconrel.2020.12.050.