期刊
JOURNAL OF CONTROLLED RELEASE
卷 330, 期 -, 页码 738-752出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2020.12.050
关键词
Nanoparticle networks; Starch; Hydrogel; Intranasal; Antipsychotics; Schizophrenia; In situ-gelling; Sprayable
资金
- Natural Sciences and Engineering Research Council of Canada (NSERC, Collaborative Health Research Partnership grant) [CHRPJ508393-2017]
- Canadian Institutes for Health Research (CIHR, Collaborative Health Research Partnership grant) [CPG-151963]
Intranasal delivery of peptide drug PAOPA via novel nanoparticle hydrogels shows prolonged therapeutic effects in a rat model of schizophrenia, offering potential for reduced drug doses and administration frequencies.
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. 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.
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