Mixed Materials
Pharmacokinetic Study of Fingolimod Nasal Films Administered via Nose-to-Brain Route in C57BL/6 J Mice as Potential Treatment for Multiple Sclerosis
| Τίτλος: | Pharmacokinetic Study of Fingolimod Nasal Films Administered via Nose-to-Brain Route in C57BL/6 J Mice as Potential Treatment for Multiple Sclerosis |
|---|---|
| Additional Titles: | Background: Fingolimod hydrochloride (FH) has emerged as a vital medication for managing Multiple Sclerosis (MS). Despite its high oral bioavailability of 93%, it is plagued by slow oral absorption (Tmax = 8–12 h) and extensive hepatic metabolism. Intranasal administration has emerged as an alternative to address these limitations, ensuring efficient central nervous system delivery and minimizing peripheral exposure and first-pass metabolism. Objective: This study aims to develop and evaluate FH nasal films for enhanced drug delivery. Methods: A Design of Experiments approach was employed to formulate FH nasal films, utilizing HPMC E50 as a film-forming polymer, PEG 400 as a plasticizer, and Me-β-CD as a permeation enhancer. Two formulations with superior in vitro and ex vivo performance were selected for in vivo evaluation. A comparative pharmacokinetic study was conducted in C57BL/6 J mice in the brain and serum after administration of nasal films and oral FH solution, respectively. Sparse sampling and non-compartmental analysis were used. Results: FH nasal films efficiently delivered the drug to both serum (Cmax(F3) = 0.35 ± 0.021, Cmax(F4) = 0.38 ± 0.029 μg/mL) and brain (Cmax(F3) = 0.39 ± 0.05, Cmax(F4) = 0.44 ± 0.048 μg/mL), achieving higher levels than oral delivery. Brain relative bioavailability (% Frel (0-6 h)) was 519% and 534%, while serum % Frel (0-6 h) was 295% and 343%. Conclusions: The rapid nose-to-brain delivery within 30 min, in contrast to 10-h Tmax of the oral solution, indicates the potential of a combined IN and oral treatment regimen. This approach could expedite the attainment of steady-state concentrations, offering a promising method for managing multiple sclerosis (MS). Graphical Abstract: (Figure presented.) © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. |
| Συγγραφείς: | Papakyriakopoulou, Paraskevi, Balafas, Evangelos, Kostomitsopoulos, Nikolaos, Rekkas, Dimitrios M., Dev, Kumlesh K., Valsami, Georgia |
| Στοιχεία εκδότη: | 2024 |
| Τύπος εγγράφου: | Mixed materials |
| Όροι ευρετηρίου: | scientific_publication_article, Scientific publication - Journal Article |
| Σύνδεσμος: | |
| Διαθεσιμότητα: | Open access content. Open access content Creative Commons Attribution-NonCommercial 4.0 (CC-BY-NC) |
| Σημείωση: | English |
| Other Numbers: | GRNKU oai:lib.uoa.gr:uoadl:3491635 uoadl:3491635 1523434331 |
| Πηγή συνεισφοράς: | NATIONAL & KAPODISTRIAN UNIV OF ATHENS From OAIster®, provided by the OCLC Cooperative. |
| Αριθμός Καταχώρησης: | edsoai.on1523434331 |
| Βάση Δεδομένων: | OAIster |
| Η περιγραφή δεν είναι διαθέσιμη |