Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent
Ayoub, Bassam M; Mowaka, Shereen; Safar, Marwa M; Ashoush, Nermeen; Arafa, Mona G; Effat, Haidy; Tadros, Mariam M; Elmazar, Mohamed M; Mousa, Shaker A;
Abstract
Drug repositioning is a revolution breakthrough of drug discovery that presents outstanding privilege with already safer agents by scanning the existing candidates as therapeutic switching or repurposing for marketed drugs. Sitagliptin, vildagliptin, saxagliptin & linagliptin showed antioxidant and neurorestorative effects in previous studies linked to DPP-4 inhibition. Literature showed that gliptins did not cross the blood brain barrier (BBB) while omarigliptin was the first gliptin that crossed it successfully in the present work. LC-MS/MS determination of once-weekly anti-diabetic DPP-4 inhibitors; omarigliptin & trelagliptin in plasma and brain tissue was employed after 2 h of oral administration to rats. The brain/plasma concentration ratio was used to deduce the penetration power through the BBB. Results showed that only omarigliptin crossed the BBB due to its low molecular weight & lipophilic properties suggesting its repositioning as antiparkinsonian agent. The results of BBB crossing will be of interest for researchers interested in Parkinson's disease. A novel intranasal formulation was developed using sodium lauryl sulphate surfactant to solubilize the lipophilic omarigliptin with penetration enhancing & antimicrobial properties. Intranasal administration showed enhanced brain/plasma ratio by 3.3 folds compared to the oral group accompanied with 2.6 folds increase in brain glucagon-like peptide-1 concentration compared to the control group.
Other data
Title | Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent | Authors | Ayoub, Bassam M; Mowaka, Shereen; Safar, Marwa M; Ashoush, Nermeen; Arafa, Mona G; Effat, Haidy ; Tadros, Mariam M; Elmazar, Mohamed M; Mousa, Shaker A | Keywords | DIPEPTIDYL PEPTIDASE-4 INHIBITOR;MASS-SPECTROMETRY METHOD;HIV-PROTEASE INHIBITORS;WEEKLY DPP-4 INHIBITOR;LC-MS/MS METHOD;BRAIN-TISSUE;RAT PLASMA;MOUSE PLASMA;COLON-CANCER;DRUG | Issue Date | 2018 | Publisher | NATURE PUBLISHING GROUP | Journal | Scientific Reports | ISSN | 2045-2322 | DOI | 10.1038/s41598-018-27395-0 | PubMed ID | 29895906 | Web of science ID | WOS:000434920800003 |
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