Topotecan microneedle scleral patch: A transscleral drug delivery study for retinoblastoma

<h2>Abstract</h2><h3>Purpose</h3> We aimed to design, fabricate, and evaluate the pharmacokinetic properties of topotecan loaded with microneedle scleral patch (MSP) in rabbit eye. <h3>Methods</h3> The MSP was fabricated using a 3D-printed master mold. The second step involved making polydimethylsiloxane mold using a Sylgard 184 Silicone Elastomer Kit. MSP was fabricated using a high-molecular-weight sodium hyaluronate biopolymer containing 90 conical microneedles (MN) in a 15 × 6 array format. MSP was loaded with 100 μg of topotecan to study its pharmacokinetics across choroid-retina complex. <h3>Results</h3> 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 <i>ex vivo</i> 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 <i>in vivo</i> rabbit model (9 eyes), topotecan levels peaked at 1 h (2.75±2 μg/mL) and decreased at 2 h (0.64±0.3 μg/mL), attaining 200 times the therapeutic target level. At 8 h, the drug level was undetectable (0.02±0.01 μg/mL). The patch completely dissolved within 2-4 min with unchanged fundus appearance and no retinal toxicity. <h3>Conclusions</h3> A single topotecan-loaded MSP (100 μg) achieved highly selective retinal tissue distribution, with a retinal-to-plasma ratio 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.