Therapeutic potential of phosphodiesterase inhibitor-loaded nanomicelles to treat endotoxin-induced anterior uveitis
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [177]
Cites
Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2)
Honary, S., & Zahir, F. (2013) · Tropical Journal of Pharmaceutical Research · doi:10.4314/tjpr.v12i2.20 · Cited by 1,310 · see citing works
Mandal, A., Bisht, R., Rupenthal, I. D., & Mitra, A. K. (2017) · Journal of Controlled Release · doi:10.1016/j.jconrel.2017.01.012 · Cited by 481 · see citing works
Apremilast mechanism of action and application to psoriasis and psoriatic arthritis
Schafer, P. H. (2012) · Biochemical Pharmacology · doi:10.1016/j.bcp.2012.01.001 · Cited by 440 · see citing works
Schafer, P., Parton, A., Gandhi, A., Capone, L., Adams, M., Wu, L., Bartlett, J., Loveland, M., Gilhar, A., Cheung, Y., et al. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2009.00559.x · Cited by 414 · see citing works
The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases
Raker, V., Becker, C., & Steinbrink, K. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00123 · Cited by 321 · see citing works
Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity
Schafer, P. H., Parton, A., Capone, L., Cedzik, D., Brady, H. A., Evans, J. F., Man, H., Muller, G. W., Stirling, D., & Chopra, R. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.05.014 · Cited by 311 · see citing works
Barisani‐Asenbauer, T., Maca, S. M., Mejdoubi, L., Emminger, W., Machold, K. P., & Auer, H. (2012) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-7-57 · Cited by 252 · see citing works
Pandit, J., Sultana, Y., & Aqil, M. (2016) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2016.1243545 · Cited by 134 · see citing works
Phosphodiesterase 4 inhibitors
Zebda, R., & Paller, A. S. (2017) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2017.11.056 · Cited by 126 · see citing works
In situ gelling dorzolamide loaded chitosan nanoparticles for the treatment of glaucoma.
Katiyar, S., Pandit, J., Mondal, R. S., Mishra, A., Chuttani, K., Aqil, M., Ali, A., & Sultana, Y. (2014) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2013.10.079 · Cited by 104 · see citing works
How do polymeric micelles cross epithelial barriers?
Pepić, I., Lovrić, J., & Filipović-Grčić, J. (2013) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2013.04.012 · Cited by 102 · see citing works
Apremilast: A Novel Oral Treatment for Psoriasis and Psoriatic Arthritis
Torres, T., & Puig, L. (2017) · American Journal of Clinical Dermatology · doi:10.1007/s40257-017-0302-0 · Cited by 95 · see citing works
Thermodynamics of Sodium Dodecyl Sulfate (SDS) Micellization: An Undergraduate Laboratory Experiment
Marcolongo, J. P., & Mirenda, M. (2011) · Journal of Chemical Education · doi:10.1021/ed900019u · Cited by 91 · see citing works
Pérez‐Aso, M., Montesinos, M. C., Mediero, A., Wilder, T., Schafer, P. H., & Cronstein, B. N. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0771-6 · Cited by 89 · see citing works
Di Tommaso, C., Torriglia, A., Furrer, P., Behar-Cohen, F., Gurny, R., & Möller, M. (2011) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2011.01.004 · Cited by 84 · see citing works
In vitro and ex vivo correlation of drug release from ophthalmic ointments
Bao, Q., Newman, B. W., Wang, Y., Choi, S. H., & Burgess, D. J. (2018) · Journal of Controlled Release · doi:10.1016/j.jconrel.2018.03.003 · Cited by 84 · see citing works
Rafie, F., Javadzadeh, Y., Javadzadeh, A., Ghavidel, L. A., Jafari, B., Moogooee, M., & Davaran, S. (2010) · Current Eye Research · doi:10.3109/02713683.2010.508867 · Cited by 83 · see citing works
Retino-Choroidal Changes in Endotoxin-Induced Uveitis in the Rat
Ruiz‐Moreno, J. M., Thillaye-Goldenberg, B., & de Kozak, Y. (2009) · Ophthalmic Research · doi:10.1159/000267163 · Cited by 82 · see citing works
The Role of Nitric Oxide in Uveitis
Parks, D. J. (1994) · Archives of Ophthalmology · doi:10.1001/archopht.1994.01090160124032 · Cited by 80 · see citing works
Guo, C., Zhang, Y., Yang, Z., Li, M., Li, F., Cui, F., Liu, T., Shi, W., & Wu, X. (2015) · Scientific Reports · doi:10.1038/srep12968 · Cited by 80 · see citing works
Madan, J., Khobaragade, S., Dua, K., & Awasthi, R. (2020) · Dermatologic Therapy · doi:10.1111/dth.13370 · Cited by 78 · see citing works
Prodrugs and nanomicelles to overcome ocular barriers for drug penetration
Gote, V., Michael, A., & Pal, D. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1803278 · Cited by 73 · see citing works
Immunosuppressive therapy for chronic uveitis: optimising therapy with steroids and cyclosporin A
Dick, A. D., Azim, M., & Forrester, J. V. (1997) · British Journal of Ophthalmology · doi:10.1136/bjo.81.12.1107 · Cited by 67 · see citing works
PLGA nanoparticles for ocular delivery of loteprednol etabonate: a corneal penetration study
Sah, A. K., Suresh, P. K., & Verma, V. K. (2016) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2016.1203794 · Cited by 67 · see citing works
Ashjari, M., Khoee, S., Mahdavian, A. R., & Rahmatolahzadeh, R. (2012) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-012-4562-1 · Cited by 62 · see citing works
Chen, Y., Li, Z., Li, H., Su, W., Xie, Y., Pan, Y., Chen, X., & Liang, D. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.581673 · Cited by 61 · see citing works
Medical Management of Uveitis - Current Trends
Babu, K., & Mahendradas, P. (2013) · Indian Journal of Ophthalmology · doi:10.4103/0301-4738.114099 · Cited by 59 · see citing works
Novel nanocrystal-based formulations of apremilast for improved topical delivery
Parmar, P. K., & Bansal, A. K. (2020) · Drug Delivery and Translational Research · doi:10.1007/s13346-020-00809-1 · Cited by 56 · see citing works
Optimization of Dexamethasone Mixed Nanomicellar Formulation
Cholkar, K., Hariharan, S., Gunda, S., & Mitra, A. K. (2014) · AAPS PharmSciTech · doi:10.1208/s12249-014-0159-y · Cited by 55 · see citing works
Mahdi, W. A., Bukhari, S. I., Imam, S. S., Alshehri, S., Zafar, A., & Yasir, M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13071087 · Cited by 53 · see citing works
Rapalli, V. K., Tomar, Y., Sharma, S., Roy, A., & Singhvi, G. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114634 · Cited by 52 · see citing works
Raval, N., Khunt, D., & Misra, M. (2018) · Journal of Microencapsulation · doi:10.1080/02652048.2018.1425750 · Cited by 49 · see citing works
Ke, Z., Zhang, Z., Wu, H., Jia, X., & Wang, Y. (2016) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2016.12.047 · Cited by 47 · see citing works
Lipopolysaccharide-induced inflammation increases nitric oxide production in taste buds
Wu, Z., Huang, Y., Hu, W., Ren, L., Jiang, P., Margolskee, R. F., Wang, H., & Feng, S. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.04.016 · Cited by 47 · see citing works
Ahmed, T. A., El‐Say, K. M., Ahmed, O. A. A., & Aljaeid, B. M. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s213086 · Cited by 46 · see citing works
Zhou, T., Zhu, L., Xia, H., He, J., Liu, S., He, S., Wang, L., & Zhang, J. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.08.020 · Cited by 45 · see citing works
Wu, L., Li, X., Wu, H., Long, W., Jiang, X., Shen, T., Qiang, Q., Si, C., Wang, X., Jiang, Y., et al. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030315 · Cited by 38 · see citing works
HET-CAM test for determining the possible eye irritancy of pesticides
Budai, P., Lehel, J., Tavaszi, J., & Kormos, É. (2010) · Acta Veterinaria Hungarica · doi:10.1556/avet.58.2010.3.9 · Cited by 35 · see citing works
Polymeric micelles as a novel carrier for ocular drug delivery
Özsoy, Y., Güngör, S., Kahraman, E., & Durgun, M. E. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816200-2.00005-0 · Cited by 27 · see citing works
Lu, P., Liang, Z. C., Zhang, Z., Yang, J., Song, F., Zhou, T., Li, J., & Zhang, J. (2023) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2023.106629 · Cited by 27 · see citing works
To Enhance Mucus Penetration and Lung Absorption of Drug by Inhalable Nanocrystals-In-Microparticles
Huang, G. S., Shuai, S., Zhou, W., Chen, Y., Shen, B., & Yue, P. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14030538 · Cited by 26 · see citing works
Veeren, A., Bhaw‐Luximon, A., Mukhopadhyay, D., & Jhurry, D. (2017) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2017.03.021 · Cited by 23 · see citing works
Wu, M., Kao, I.-F., Fu, C., & Yen, S. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15082025 · Cited by 23 · see citing works
Nanomicelles empower natamycin in treating fungal keratitis: An in vitro, ex vivo and in vivo study
Sathe, P., Kailasam, V., Nagarjuna, V., Sharma, H. P., Velpandian, T., Garg, P., & Nirmal, J. (2024) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2024.124118 · Cited by 22 · see citing works
Self-citationNalinbenjapun, S., Sripetthong, S., Basit, A., Suksuwan, A., Sajomsang, W., & Ovatlarnporn, C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135904 · Cited by 21 · see citing works
Kailasam, V., Kumara, B. N., Prasad, K. S., & Nirmal, J. (2024) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2024.114208 · Cited by 19 · see citing works
Self-citationRole of CD4+ T cell-derived cytokines in the pathogenesis of uveitis
Meng, T., Nie, L., & Wang, Y. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01565-7 · Cited by 19 · see citing works
Lu, Y., Shen, X., Hang, T., & Song, M. O. (2017) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2017.03.067 · Cited by 18 · see citing works
Muvva, A., Yarlagadda, D. L., Dwibhashyam, V. S. N. M., Dengale, S. J., & Lewis, S. A. (2020) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2020.101844 · Cited by 18 · see citing works
Anti-inflammatory effects of vitamin E on experimental lens-induced uveitis
Cid, L., Pararajasegaram, G., Sevanian, A., Gauderman, W. J., Romero, J. L., Marak, G. E., & Rao, N. A. (1992) · International Ophthalmology · doi:10.1007/bf00917069 · Cited by 17 · see citing works
Regulatory T Cells: Therapeutic Opportunities in Uveitis
Lee, A. Y., & Foulsham, W. (2022) · Frontiers in Ophthalmology · doi:10.3389/fopht.2022.901144 · Cited by 15 · see citing works
Campanati, A., Caffarini, M., Diotallevi, F., Radi, G., Lucarini, G., Vincenzo, M. D., Orciani, M., & Offidani, A. (2020) · Inflammation Research · doi:10.1007/s00011-020-01412-3 · Cited by 10 · see citing works
Anti-Inflammatory Effects of GM1 Ganglioside on Endotoxin-Induced Uveitis in Rats
Weng, T., Ke, C.-C., & Huang, Y. (2022) · Biomolecules · doi:10.3390/biom12050727 · Cited by 10 · see citing works
Treatment of Uveitis—An Overview
Foster, C. S., & Vitale, A. T. (2013) · Jaypee Brothers Medical Publishers (P) Ltd. eBooks · doi:10.5005/jp/books/11822_8 · Cited by 8 · see citing works
Su, L., Yu, Z., & Zhao, W. (2025) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.14151 · Cited by 8 · see citing works
Retinal Pathophysiological Evaluation in a Rat Model
Malani, M., & Nirmal, J. (2022) · Journal of Visualized Experiments · doi:10.3791/63111 · Cited by 7 · see citing works
Self-citationSutar, K. P., Jalalpure, S. S., & Kurangi, B. K. (2024) · Separation Science Plus · doi:10.1002/sscp.202400070 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics
Sun, M., Wang, J., Fan, W., Wang, K., Wang, Y., Zhang, J., Ding, S., Zhang, C., Feng, Z., Wang, Y.-G., et al. (2025) · Materials today. Bio · doi:10.1016/j.mtbio.2025.102537 · Cited by 7 · see citing works
“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].”
Kondapaneni, L. P., Choudhury, N., Asenso, J., Arora, M., Kumar, M. N. V. R., & Ganugula, R. (2026) · Research Square · doi:10.21203/rs.3.rs-11132123/v1
Management strategies of noninfectious scleritis: An update
Sheth, J. U., Murthy, S. I., & Karande, S. (2026) · Indian Journal of Ophthalmology · doi:10.4103/ijo.ijo_1004_26
- 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
- Licence
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review