In vivo intranasal delivery of coagulation factor IX: a proof-of-concept study.
J Thromb Haemost
; 21(11): 3117-3123, 2023 11.
Article
in En
| MEDLINE
| ID: mdl-37633640
ABSTRACT
BACKGROUND:
Hemophilia B (HB) is a bleeding disorder characterized by coagulation factor (F) IX (FIX) deficiency. The current standard-of-care for severe HB is prophylaxis with long-term repetitive intravenous (i.v.) infusions of recombinant FIX (rFIX) with standard half-life or extended half-life. Unmet needs remain regarding the development of non-invasive administration routes for coagulation factors. The aim of this study was to evaluate the effectiveness of intranasal delivery (IND) of rFIX and rFIX fused to Fc fragment (rFIX-Fc) in mice.METHODS:
Drops of rFIX and rFIX-Fc were deposited in the nostrils of wild-type, FcRn knock-out, FcRn humanized, and FIX knock-out mice. rFIX mucosal uptake was evaluated by measuring plasma FIX antigen and FIX activity (FIXC) levels, and by performing histologic analysis of the nasal mucosa following IND.RESULTS:
After IND, both rFIX and rFIX-Fc were equally delivered to the blood compartment, irrespective of the mouse strain studied, mostly through a passive mechanism of transportation across the mucosal barrier, independent of FcRn receptor. Both plasma FIX antigen and FIXC activity levels increased following IND in FIX knock-out mice.CONCLUSION:
This proof-of-concept study describes evidence supporting the nasal route as an alternative to FIX i.v. infusion for the treatment of HB.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hemophilia B
/
Hemophilia A
Limits:
Animals
Language:
En
Journal:
J Thromb Haemost
Journal subject:
HEMATOLOGIA
Year:
2023
Document type:
Article