Computer-aided rational design for optimally Gantrez® S-97 and hyaluronic acid-based dissolving microneedles as a potential ocular delivery system

Abstract

Dissolving microneedles (DMNs) uses micron-scale technology that is minimally invasive for ocular drug delivery. The purpose of this study was to design and develop the optimal DMNs as a potential delivery system for ocular application. Computational design strategy by central composite design-response surface methodology (CCD-RSM) was used to design and select the optimal formulation. Fluorescein sodium (FS), a model hydrophilic compound, was loaded in DMNs. Gantrez® S-97 (GAN) and hyaluronic acid (HA) polymer in various ratios were used to fabricate DMNs. The physical and mechanical properties, ocular permeation, FS remaining in ocular tissue, dissolution time, insertion force, insertion depth and ex vivo ocular drug delivery were evaluated. From the results, the optimal DMNs formulation was 20.06%GAN+5%HA+1%FS that showed the conical-shaped with 11 × 11 MN arrays around 570.83 ± 14.78 μm in height, 300.23 ± 3.30 μm in width, and 600.10 ± 2.12 μm in interspacing with 25 mm2 of patch area. The optimal DMNs had appropriate properties with 25.42 ± 0.72% in height reduction, 52.15 ± 20.59% in FS permeation in 24 h, and 2.42 ± 0.21% of FS remaining in ocular tissue. DMNs completely dissolved in sclera tissue within 2 min. The insertion force needed for 100% insertion was 0.08 N/needle and the insertion depth was around 200–400 μm. In the ex vivo study, the optimal DMNs showed FS permeation in 24 h being higher than patch (control), indicating the ability to overcome the eye barrier and deliver FS into the eye. In conclusion, the optimal DMNs presented suitable minimally invasive microneedle properties for an effective ocular drug delivery system.