PMID- 35194614
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
DP  - 2022 Feb 17
TI  - Safety and Pharmacokinetics of Intranasally Administered Heparin.
LID - 2021.07.05.21259936 [pii]
LID - 10.1101/2021.07.05.21259936 [doi]
AB  - PURPOSE: Intranasally administered unfractionated heparin (UFH) and other 
      sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of 
      this research was to measure the safety and pharmacokinetics of clearance of 
      intranasally administered UFH solution from the nasal cavity. METHODS: 
      Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 
      60 mug) of UFH was carried out for fourteen consecutive days, with both blood 
      coagulation measurements and subject adverse event monitoring. The 
      pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were 
      measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with 
      nasal spray device was tested for safety in a small number of healthy human 
      subjects. RESULTS: UFH showed no evidence of toxicity in mice at any dose 
      measured. No significant changes were observed in activated partial 
      thromboplastin time (aPTT), platelet count, or frequency of minor irritant events 
      over vehicle-only control. Human subjects showed no significant changes in aPTT 
      time, international normalized ratio (INR), or platelet count over baseline 
      measurements. No serious adverse events were observed. In vivo imaging in a mouse 
      model showed a single phase clearance of UFH from the nasal cavity. After 12 
      hours, 3.2% of the administered UFH remained in the nasal cavity, decaying to 
      background levels by 48 hours. CONCLUSIONS: UFH showed no toxic effects for 
      extended daily intranasal dosing in mice as well as humans. The clearance 
      kinetics of intranasal heparin solution from the nasal cavity indicates 
      potentially protective levels for up to 12 hours after dosing.
FAU - Harris, Hannah M
AU  - Harris HM
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Boyet, Katherine L
AU  - Boyet KL
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Liu, Hao
AU  - Liu H
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Dwivedi, Rohini
AU  - Dwivedi R
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Ashpole, Nicole M
AU  - Ashpole NM
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Tandon, Ritesh
AU  - Tandon R
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
AD  - Department of Medicine, University of Mississippi Medical Center, Jackson, MS 
      39216.
FAU - Bidwell, Gene L 3rd
AU  - Bidwell GL 3rd
AD  - Department of Neurology, University of Mississippi Medical Center, Jackson, MS 
      39216.
FAU - Cheng, Zhi
AU  - Cheng Z
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Fassero, Lauren A
AU  - Fassero LA
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Yu, Christian S
AU  - Yu CS
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Pomin, Vitor H
AU  - Pomin VH
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
FAU - Mitra, Dipanwita
AU  - Mitra D
AD  - Department of Microbiology and Immunology, University of Mississippi Medical 
      Center, Jackson, MS 39216.
FAU - Harrison, Kerri A
AU  - Harrison KA
AD  - National Center for Natural Products Research, University of Mississippi, Oxford, 
      MS 38677.
FAU - Dahl, Eric
AU  - Dahl E
AD  - National Center for Natural Products Research, University of Mississippi, Oxford, 
      MS 38677.
FAU - Gurley, Bill J
AU  - Gurley BJ
AD  - National Center for Natural Products Research, University of Mississippi, Oxford, 
      MS 38677.
FAU - Kotha, Arun Kumar
AU  - Kotha AK
AD  - Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, 
      MS 38677.
AD  - Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341.
FAU - Chougule, Mahavir Bhupal
AU  - Chougule MB
AD  - Department of Pharmaceutics and Drug Delivery, University of Mississippi, Oxford, 
      MS 38677.
AD  - Department of Pharmaceutical Sciences, Mercer University, Atlanta, GA 30341.
FAU - Sharp, Joshua S
AU  - Sharp JS
AD  - Department of BioMolecular Sciences, University of Mississippi, Oxford, MS 38677.
AD  - Department of Chemistry and Biochemistry, University of Mississippi, Oxford, MS 
      38677.
LA  - eng
GR  - 80NSSC18K1603/ImNASA/Intramural NASA/United States
GR  - P30 GM122733/GM/NIGMS NIH HHS/United States
PT  - Preprint
DEP - 20220217
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - Pharm Res. 2022 Mar 2;:. PMID: 35237922
PMC - PMC8863150
COIS- Conflict of Interest Statement The authors declare no conflicts of interest.
EDAT- 2022/02/24 06:00
MHDA- 2022/02/24 06:01
PMCR- 2022/02/22
CRDT- 2022/02/23 05:34
PHST- 2022/02/23 05:34 [entrez]
PHST- 2022/02/24 06:00 [pubmed]
PHST- 2022/02/24 06:01 [medline]
PHST- 2022/02/22 00:00 [pmc-release]
AID - 2021.07.05.21259936 [pii]
AID - 10.1101/2021.07.05.21259936 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2022 Feb 17:2021.07.05.21259936. doi: 
      10.1101/2021.07.05.21259936.