Cited by 3Advanced Drug Delivery SystemsOcular Diseases and Behçet’s SyndromeOcular Infections and Treatments

Therapeutic potential of phosphodiesterase inhibitor-loaded nanomicelles to treat endotoxin-induced anterior uveitis

Kailasam, Velmurugan, Malani, Manisha, Nirmal, Jayabalan·2025·International Journal of Pharmaceutics

Abstract

Uveitis is an ocular inflammatory condition that can be infectious or non-infectious, affecting various ocular structures. Corticosteroids and immunomodulators are the current standard of care for treating anterior uveitis, which has side effects such as cataracts and increased intraocular pressure. Therefore, a continuous search is going on to find an alternate strategy (steroid-sparing agent) to treat uveitis with improved safety. Apremilast, a phosphodiesterase-4 (PDE-4) inhibitor, has an anti-inflammatory activity, which could regulate the production of inflammatory mediators such as TNF-alpha and nitric oxide by inhibiting the conversion of cyclic adenosine monophosphate to adenosine monophosphate. A dose-inverted therapeutic effect was observed for Apremilast to treat acute anterior uveitis in an endotoxin-induced uveitis rat model. Further, to address the poor solubility and permeability, Apremilast-loaded nanomicelles (Aprecel) were developed and thoroughly characterized. Ocular pharmacokinetics study indicates that the developed nanomicelles facilitated the permeation of Apremilast across the corneal barrier due to increased solubility and residence time. Also, an in vivo efficacy study shows that the developed Aprecel effectively reduces the cell infiltration and protein levels in the endotoxin-induced uveitis rat model, along with inflammatory cytokines such as TNF-alpha. Therefore, Apremilast-loaded nanomicelles could be used as a potential steroid-sparing alternative to treat acute anterior uveitis with reduced side effects.

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Crossref · 10.1016/j.ijpharm.2025.126162

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  • Apremilast-loaded nanomicelles (Aprecel) can effectively alleviate the inflammatory response in the endotoxin-induced anterior uveitis rat model, providing a safe and effective steroid replacement treatment option for acute anterior uveitis.

    “Both in vivo and in vitro experiments have confirmed that it can effectively alleviate the inflammatory response in the endotoxin-induced anterior uveitis rat model, providing a safe and effective steroid replacement treatment option for acute anterior uveitis [177].”

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Authors
Kailasam, V., Malani, M., & Nirmal, J.
Affiliations
Birla Institute of Technology and Science - Hyderabad Campus (IN)
Corresponding author
Nirmal, Jayabalan
Venue
International Journal of Pharmaceutics
Publisher
Elsevier BV
Published
2025-11
Volume
684
Pages
126162
ISSN
0378-5173 (ISSN-L)
OpenAlex
W4414107753
Cited by
3
References
57
Citations by year
2026: 2 · 2025: 1
FWCI
1.26
Type
journal article
Language
en
Open access
closed
Locations
  • International Journal of Pharmaceutics (publishedVersion)
  • PubMed (publishedVersion)
Funders
Department of Science and Technology, Ministry of Science and Technology, India
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
Keywords
anterior uveitis, apremilast, phosphodiesterase-4 inhibitors, nanomicelles, endotoxin-induced uveitis, steroid-sparing therapy, ocular drug delivery, ocular pharmacokinetics, corneal permeation, TNF-α, anti-inflammatory drug delivery, ocular inflammation
MeSH terms
Animals, Disease Models, Animal, Endotoxins, Male, Micelles, Thalidomide, Tumor Necrosis Factor-alpha, Uveitis, Anterior, Rats, Sprague-Dawley, Rats, Nanoparticles, Phosphodiesterase 4 Inhibitors

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