Topotecan Microneedle Scleral Patch: A Transscleral Drug Delivery Study for Retinoblastoma

We aimed to design, fabricate, and evaluate the pharmacokinetic properties of topotecan loaded with microneedle scleral patch (MSP) in rabbit eye.

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.

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.

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.

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.