Biomimetic nanomicelles: utilizing peptide transporters to overcome corneal barrier for treating fungal infection
Abstract
The corneal barrier restricts the entry of xenobiotics (including drugs) in the anterior segment of the eye, resulting in less than 5% of the drug reaching the target site (deep corneal tissues) – necessitating frequent topical eye drop administration. Interestingly, despite these barriers, endogenous peptides are shuttled across the cornea by peptide transporters expressed on the corneal epithelium. The current study investigates the potential of targeting peptide transporters to increase the permeability of poorly permeable drugs across the cornea. D-α-tocopherol polyethylene glycol succinate (TPGS), an amphiphilic polymer, was conjugated with Glycyl-Sarcosine (Gly-Sar), a well-known peptide transporter ligand to develop nanomicelles. Natamycin, a poorly water-soluble and poorly permeable drug, was entrapped (0.6%) in Gly-Sar-TPGS-formulated nanomicelles. Both ex vivo and in vivo studies demonstrated that the natamycin-loaded Gly-Sar-TPGS nanomicelles (PeNatcel) enhanced permeation across the cornea. The PeNatcel demonstrated therapeutic efficiency against Candida albicans and Aspergillus flavus using in vitro and ex vivo antifungal studies. PeNatcel showed comparable activity against Candida albicans at 4 times a day dosing frequency compared to 12 times a day marketed 5% natamycin suspension. Consequently, the developed peptide transporter-specific ligand-conjugated nanomicelles delivery system can also be explored further for other water-insoluble and poorly permeable drugs.
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Gly-Sar-TPGS nanomicelles (PeNatcel) significantly enhanced corneal permeation and exhibited potent antifungal efficacy against Candida albicans and Aspergillus flavus.
“When loaded with natamycin, the resulting Gly-Sar-TPGS nanomicelles (PeNatcel) significantly enhanced corneal permeation and exhibited potent antifungal efficacy against Candida albicans and Aspergillus flavus.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [142]
PeNatcel achieved comparable therapeutic activity with only 4 daily administrations, in contrast to the 12 doses required by a commercial 5% natamycin suspension.
“Importantly, PeNatcel achieved comparable therapeutic activity with only 4 daily administrations, in contrast to the 12 doses required by a commercial 5 % natamycin suspension [142].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [142]
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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
“Importantly, PeNatcel achieved comparable therapeutic activity with only 4 daily administrations, in contrast to the 12 doses required by a commercial 5 % natamycin suspension [142].”
Artificial Intelligence in Corneal Drug Delivery Systems
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Hu, Y., Li, Y., Wu, Y., Zhu, Y., Chen, J., Ding, Y., Yang, Z., & Li, X. (2026) · Drug Delivery · doi:10.1080/10717544.2026.2677302
- Authors
- Sathe, P., Nagarjuna, V., Sharma, H., Velpandian, T., Garg, P., & Nirmal, J.
- Affiliations
- Birla Institute of Technology and Science - Hyderabad Campus (IN)
- L V Prasad Eye Institute (IN)
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Nirmal, Jayabalan
- Venue
- Molecular Pharmaceutics
- Publisher
- American Chemical Society (ACS)
- Published
- 2025-10-20
- Volume
- 22
- Issue
- 11
- Pages
- 6575-6587
- ISSN
- 1543-8384 (ISSN-L)
- 1543-8392
- OpenAlex
- W4415368501
- Cited by
- 3
- References
- 64
- Citations by year
- 2026: 2 · 2025: 1
- FWCI
- 1.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indian Council of Medical Research (5/3/8/21/ITR-F/2020-ITR)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- peptide transporters, corneal permeation, nanomicelles, TPGS, natamycin, antifungal drug delivery, Candida albicans, Aspergillus flavus, corneal epithelium, poorly water-soluble drugs, corneal barrier, topical ocular drug delivery
- MeSH terms
- Animals, Antifungal Agents, Aspergillus flavus, Candida albicans, Cornea, Humans, Micelles, Peptides, Permeability, Natamycin, Rabbits, Vitamin E, Drug Delivery Systems, Epithelium, Corneal, Biomimetics, Biomimetic Materials, Nanoparticles
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