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Meibomian Gland-Mediated Drug Delivery via Eyelid Application of Troxipide Nanoparticles Improves an N-Acetylcysteine-Induced Dry Eye

delete2026-08-11
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OA
AI
H
Hiroko Otake
R
Rie Tanaka
F
Fumihiko Ogata
M
Manju Misra
K
K. Kánai
M
Masanobu Tsubaki
N
Naoki Yamamoto
N
Naohito Kawasaki
N
Noriaki Nagai *
DOI:10.3390/pharmaceutics18080973delete
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Abstract

Abstract

En 中文
Background/Objectives: Dry eye disease (DED) is a multifactorial disorder characterized by tear film instability, inflammation, and ocular surface damage, which significantly impairs visual function and quality of life. Conventional ophthalmic formulations, such as eye drops, have low bioavailability owing to rapid elimination, necessitating frequent administration. In this study, we developed an eyelid-applied drug delivery system (DDS) based on troxipide (TRO) nanoparticle formulation (TRO-NP@EG) to achieve sustained ocular surface delivery. Methods: TRO nanosuspensions were prepared by wet bead milling and incorporated into a Carbopol-based gel. Particle size, dispersion stability, and uniformity were evaluated, and in vitro drug release studies was compared with that of TRO-MP@EG. In vivo drug transfer into tear fluid was assessed in rabbits following eyelid application, and therapeutic efficacy was evaluated in an N-acetylcysteine-induced dry eye model. Results: TRO nanosuspensions had a mean particle size of approximately 118 nm. TRO-NP@EG exhibited superior dispersion stability and uniformity and achieved 2.5-fold higher drug release than TRO-MP@EG, while the nanoparticles remained in solid form. In vivo studies in rabbits, TRO-NP@EG significantly enhanced drug transfer into tear fluid, primarily via the meibum pathway. Furthermore, TRO-NP@EG significantly improved mucin levels, tear secretion, and tear film stability compared with TRO-MP@EG in an N-acetylcysteine-induced dry eye model. Conclusions: These findings suggest that eyelid application of nanoparticle-based formulations enables efficient and sustained drug delivery to the ocular surface via the meibomian glands. Therefore, TRO-NP@EG represents a promising therapeutic strategy for DED, providing enhanced efficacy and a novel route of administration for ophthalmic DDSs.
Keywords:
troxipide
nanoparticle
dry eye
eyelid
ocular drug delivery

Journal

Pharmaceutics cover
Pharmaceutics
IF:
5.5
Papers:
1.4W
Citations:
6.2W

Organization

K
kitasato university
Scholars:
1.2K
Papers: 365
Citations: 0
K
kindai university
Scholars:
377
Papers: 191
Citations: 0
L
L. M. College of Pharmacy
Scholars:
26
Papers: 11
Citations: 0
T
Tokushima Bunri University
Scholars:
837
Papers: 706
Citations: 502
F
fujita health university
Scholars:
1.1K
Papers: 327
Citations: 1
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