Τίτλος:
Flurbiprofen sodium microparticles and soft pellets for nose-to-brain delivery: Serum and brain levels in rats after nasal insufflation
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Neuroinflammation in Alzheimer's disease (AD) revamped the role of a preventive therapeutic action of non steroidal anti-inflammatory drugs; flurbiprofen could delay AD onset, provided its access to brain is enhanced and systemic exposure limited. Nasal administration could enable direct drug access to central nervous system (CNS) via nose-to-brain transport. Here, we investigated the insufflation, deposition, dissolution, transmucosal permeation, and in vivo transport to rat brain of flurbiprofen from nasal powders combined in an active device. Flurbiprofen sodium spray-dried microparticles as such, or soft pellets obtained by agglomeration of drug microparticles with excipients, were intranasally administered to rats by the pre-metered insufflator device. Blood and brain were collected to measure flurbiprofen levels. Excipient presence in soft pellets lowered the metered drug dose to insufflate. Nevertheless, efficiency of powder delivery by the device, measured as emitted fraction, was superior with soft pellets than microparticles, due to their coarse size. Both nasal powders resulted into rapid flurbiprofen absorption. Absolute bioavailability was 33% and 58% for microparticles and pellets, respectively. Compared to intravenous flurbiprofen, the microparticles were more efficient than soft pellets at enhancing direct drug transport to CNS. Direct Transport Percentage index evidenced that more than 60% of the intranasal dose reached the brain via direct nose-to-brain transport for both powders. Moreover, remarkable drug concentrations were measured in the olfactory bulb after microparticle delivery. Bulb connection with the entorhinal cortex, from where AD initiates, makes flurbiprofen sodium administration as nasal powder worth of further investigation in an animal model of neuroinflammation. © 2021 Elsevier B.V.
Συγγραφείς:
Tiozzo Fasiolo, L.
Manniello, M.D.
Banella, S.
Napoli, L.
Bortolotti, F.
Quarta, E.
Colombo, P.
Balafas, E.
Kostomitsopoulos, N.
Rekkas, D.M.
Valsami, G.
Papakyriakopoulou, P.
Colombo, G.
Russo, P.
Περιοδικό:
International Journal of Pharmaceutics
Λέξεις-κλειδιά:
excipient; flurbiprofen; ketamine; flurbiprofen, aeration; Alzheimer disease; analytic method; animal experiment; animal tissue; Article; brain tissue; controlled study; direct transport percentage index; drug bioavailability; drug blood level; drug brain level; drug delivery system; drug pellet; drug solubility; drug transport; entorhinal cortex; ex vivo study; fluorescence; high performance liquid chromatography; in vitro study; in vivo study; limit of detection; limit of quantitation; male; maximum concentration; nasal insufflation; nonhuman; nose mucosa; nose to brain drug delivery; olfactory bulb; particle size; powder; rat; respiratory distress; spray drying; time to maximum plasma concentration; Wistar rat; animal; brain; drug delivery system; intranasal drug administration; nose, Administration, Intranasal; Animals; Brain; Drug Delivery Systems; Flurbiprofen; Insufflation; Nose; Rats
DOI:
10.1016/j.ijpharm.2021.120827
