Ophthalmology science · 2026
Topotecan Microneedle Scleral Patch: A Transscleral Drug Delivery Study for Retinoblastoma.
СтатьяНазвание и аннотация: Перевод в очереди
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Raval Vishal, Arawindh R, Naik Sharayu, Jakati Saumya, Venuganti Venkata Vamsi Krishna
Аннотация
PURPOSE: We aimed to design, fabricate, and evaluate the pharmacokinetic properties of topotecan loaded with microneedle scleral patch (MSP) in rabbit eye.
METHODS: The MSP was fabricated using a 3-dimensional printed master mold. The second step involved making polydimethylsiloxane mold using a Sylgard 184 Silicone Elastomer Kit. The MSP was fabricated using a high-molecular-weight sodium hyaluronate biopolymer containing 90 conical microneedles (MNs) in a 15 × 6 array format. The MSP was loaded with 100 μg of topotecan to study its pharmacokinetics across choroid-retina complex.
RESULTS: The dimensions of MNs were uniform across the array measuring 548 ± 3.7 μm length, 336 ± 7.5 μm width, and 18 μm tip diameter. In the ex vivo goat eye model, the required insertion force was 0.026 N per needle, which was 50 times lower than the compression strength of 1.27 N per needle. The MNs were inserted up to a depth of 225 μm. In the in vivo rabbit model (9 eyes), topotecan levels peaked at 1 hour (2.75 ± 2 μg/g) and decreased at 2 hours (0.64 ± 0.3 μg/g), attaining 200 times the therapeutic target level. At 8 hours, the drug level was undetectable (0.02 ± 0.01 μg/g). The patch completely dissolved within 2-4 minutes with unchanged fundus appearance and no retinal toxicity.
CONCLUSIONS: A single topotecan-loaded MSP (100 μg) achieved highly selective retinal tissue distribution, with a retinal-to-plasma ratio of 275-fold, which was 4.7-fold higher than intra-arterial chemotherapy (58.9) and 209-fold higher than intravenous chemotherapy (1.32), supporting its potential benefit for RB treatment.
FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
METHODS: The MSP was fabricated using a 3-dimensional printed master mold. The second step involved making polydimethylsiloxane mold using a Sylgard 184 Silicone Elastomer Kit. The MSP was fabricated using a high-molecular-weight sodium hyaluronate biopolymer containing 90 conical microneedles (MNs) in a 15 × 6 array format. The MSP was loaded with 100 μg of topotecan to study its pharmacokinetics across choroid-retina complex.
RESULTS: The dimensions of MNs were uniform across the array measuring 548 ± 3.7 μm length, 336 ± 7.5 μm width, and 18 μm tip diameter. In the ex vivo goat eye model, the required insertion force was 0.026 N per needle, which was 50 times lower than the compression strength of 1.27 N per needle. The MNs were inserted up to a depth of 225 μm. In the in vivo rabbit model (9 eyes), topotecan levels peaked at 1 hour (2.75 ± 2 μg/g) and decreased at 2 hours (0.64 ± 0.3 μg/g), attaining 200 times the therapeutic target level. At 8 hours, the drug level was undetectable (0.02 ± 0.01 μg/g). The patch completely dissolved within 2-4 minutes with unchanged fundus appearance and no retinal toxicity.
CONCLUSIONS: A single topotecan-loaded MSP (100 μg) achieved highly selective retinal tissue distribution, with a retinal-to-plasma ratio of 275-fold, which was 4.7-fold higher than intra-arterial chemotherapy (58.9) and 209-fold higher than intravenous chemotherapy (1.32), supporting its potential benefit for RB treatment.
FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.