Nanomicellar topical aqueous drop formulation of rapamycin for back-of-the-eye delivery
Open accessAbstract
The objective of this study was to develop a clear, aqueous rapamycin-loaded mixed nanomicellar formulations (MNFs) for the back-of-the-eye delivery. MNF of rapamycin (0.2%) was prepared with vitamin E tocopherol polyethylene glycol succinate (TPGS) (Vit E TPGS) and octoxynol-40 (Oc-40) as polymeric matrix. MNF was characterized by various parameters such as size, charge, shape, and viscosity. Proton nuclear magnetic resonance ((1)H NMR) was used to identify unentrapped rapamycin in MNF. Cytotoxicity was evaluated in human retinal pigment epithelial (D407) and rabbit primary corneal epithelial cells (rPCECs). In vivo posterior ocular rapamycin distribution studies were conducted in male New Zealand white rabbits. The optimized MNF has excellent rapamycin entrapment and loading efficiency. The average size of MNF was 10.98 ± 0.089 and 10.84 ± 0.11 nm for blank and rapamycin-loaded MNF, respectively. TEM analysis revealed that nanomicelles are spherical in shape. Absence of free rapamycin in the MNF was confirmed by (1)H NMR studies. Neither placebo nor rapamycin-loaded MNF produced cytotoxicity on D407 and rPCECs indicating formulations are tolerable. In vivo studies demonstrated a very high rapamycin concentration in retina-choroid (362.35 ± 56.17 ng/g tissue). No drug was identified in the vitreous humor indicating the sequestration of rapamycin in lipoidal retinal tissues. In summary, a clear, aqueous MNF comprising of Vit E TPGS and Oc-40 loaded with rapamycin was successfully developed. Back-of-the-eye tissue distribution studies demonstrated a very high rapamycin levels in retina-choroid (place of drug action) with a negligible drug partitioning into vitreous humor.
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A clear aqueous mixed nanomicellar formulation loaded with rapamycin improves retinal drug delivery; in white rabbits, very high rapamycin levels were found in retina-choroid with negligible partitioning into vitreous humor.
“Back-of-the-eye tissue distribution studies on white rabbits demonstrated very high rapamycin levels in retina-choroid (place of drug action) with a negligible pharmacokinetic partitioning into vitreous humor [40].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [40]
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“Back-of-the-eye tissue distribution studies on white rabbits demonstrated very high rapamycin levels in retina-choroid (place of drug action) with a negligible pharmacokinetic partitioning into vitreous humor [40].”
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- Authors
- Cholkar, K., Gunda, S., Earla, R., Pal, D., & Mitra, A. K.
- Affiliations
- University of Missouri–Kansas City (US)
- Corresponding author
- Mitra, Ashim K.
- Venue
- AAPS PharmSciTech
- Published
- 2014-11-26
- Volume
- 16
- Issue
- 3
- Pages
- 610-622
- ISSN
- 1530-9932 (ISSN-L)
- PMC
- PMC4444623
- OpenAlex
- W2160165998
- Cited by
- 108
- References
- 45
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 11 · 2023: 11 · 2022: 12 · 2021: 12 · 2020: 8 · 2019: 8 · 2018: 12 · 2017: 10 · 2016: 1 · 2015: 9
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- AAPS PharmSciTech (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Missouri-Kansas City
- National Institutes of Health
- National Eye Institute (R01EY009171, R01EY09171-16, R01EY010659)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- rapamycin, vitreous humor, TPGS, retinal pigment epithelium, corneal epithelial cells, cytotoxicity, ocular tissue distribution, encapsulation efficiency, mTOR inhibitors
- MeSH terms
- Administration, Topical, Animals, Aqueous Humor, Cells, Cultured, Chemistry, Pharmaceutical, Epithelial Cells, Humans, Male, Ophthalmic Solutions, Polyethylene Glycols, Rabbits, Tissue Distribution, Vitamin E, Drug Delivery Systems, Epithelium, Corneal, Sirolimus, Retinal Pigment Epithelium, Administration, Ophthalmic
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