Fixed-Combination Eye Drops Based on Fluorometholone Nanoparticles and Bromfenac/Levofloxacin Solution Improve Drug Corneal Penetration.
bromfenac
corneal permeability
endocytosis
fixed-combination eye drops
fluorometholone
levofloxacin
Journal
International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847
Informations de publication
Date de publication:
2021
2021
Historique:
received:
24
04
2021
accepted:
22
07
2021
entrez:
20
8
2021
pubmed:
21
8
2021
medline:
25
11
2021
Statut:
epublish
Résumé
The multi-instillation of three commercially available (CA) eye drops [fluorometholone (FL)-, bromfenac (BF)- and levofloxacin (LV)-eye drops] has been used to manage pain and inflammation post-intraocular surgery. However, the multi-instillation of these three eye drops causes corneal damage, and the FL drops have the disadvantage of low ocular bioavailability. To overcome these problems, we prepared fixed-combination eye drops based on FL nanoparticles (FL-NPs) and BF/LV solution (nFBL-FC), and evaluated the corneal toxicity and transcorneal penetration of the nFBL-FC eye drops. FL powder was mixed in 2-hydroxypropyl-β-cyclodextrin solution containing benzalkonium chloride, mannitol and methylcellulose, and milled with a Bead Smash 12 (5500 rpm for 30 s×30 times). The BF/LV solution was then added to the milled-dispersions to be used as nFBL-FC. The FL, BF and LV concentrations were measured by HPLC methods, and transcorneal penetration was evaluated in rabbits. The FL particle size in nFBL-FC was 40-150 nm, with only 0.0018% in liquid form. No aggregation of FL particles in the nFBL-FC was observed for 1 month. The viability of human corneal epithelial cells treated with nFBL-FC was remarkably higher than that of cells subjected to the multi-instillation of the corresponding three CA-eye drops. In addition, the corneal penetrations (AUC) of the FL, BF and LV in nFBL-FC were 4.9-, 1.8-, and 7.1-fold those of the corresponding CA-eye drops, respectively. Moreover, the caveolae-dependent endocytosis (CavME) inhibitor (nystatin) significantly prevented the transcorneal penetration of these drugs. We prepared fixed-combination eye drops based on FL-NPs and BF/LV solution (nFBL-FC), and show that high levels of FL-NPs and dissolved BF/LV (liquid drugs) can be delivered into the aqueous humor by the instillation of nFBL-FC. Further, we show that CavME is mainly related to the enhancement of transcorneal penetration of both the solid (NPs) and liquid drugs.
Identifiants
pubmed: 34413642
doi: 10.2147/IJN.S317046
pii: 317046
pmc: PMC8369340
doi:
Substances chimiques
Benzophenones
0
Bromobenzenes
0
Ophthalmic Solutions
0
Levofloxacin
6GNT3Y5LMF
bromfenac
864P0921DW
Fluorometholone
SV0CSG527L
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5343-5356Informations de copyright
© 2021 Otake et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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