2. Academic Validation
  3. Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent

Repositioning of Omarigliptin as a once-weekly intranasal Anti-parkinsonian Agent

  • Sci Rep. 2018 Jun 12;8(1):8959. doi: 10.1038/s41598-018-27395-0.
Bassam M Ayoub 1 2,  Shereen Mowaka 3 4 5,  Marwa M Safar 4 6 7,  Nermeen Ashoush 4 8,  Mona G Arafa 4 9 10,  Haidy E Michel 11,  Mariam M Tadros 12,  Mohamed M Elmazar 4 6,  Shaker A Mousa 13
Affiliations

Affiliations

  • 1 Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt. bassam.ayoub@bue.edu.eg.
  • 2 The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt. bassam.ayoub@bue.edu.eg.
  • 3 Pharmaceutical Chemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
  • 4 The Center for Drug Research and Development (CDRD), Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
  • 5 Analytical Chemistry Department, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo, Egypt.
  • 6 Pharmacology & Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
  • 7 Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini st., Cairo, Egypt.
  • 8 Clinical Pharmacy and Pharmacy Practice Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
  • 9 Pharmaceutics Department, Faculty of Pharmacy, The British University in Egypt, El-Sherouk city, Cairo, Egypt.
  • 10 Chemotheraputic Unit, Mansoura University Hospitals, Mansoura, 35516, Egypt.
  • 11 Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, El-Abaseya, Cairo, Egypt.
  • 12 Analytical Chemistry Department, Faculty of Pharmacy, Ain Shams University, El-Abaseya, Cairo, Egypt.
  • 13 The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, United States.
PMID: 29895906 DOI: 10.1038/s41598-018-27395-0
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.

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