DNA-driven enhancement of ocular drug delivery: formulation and evaluation of diclofenac-loaded HPMC films

The use of DNA in ocular drug delivery as a polymeric bio additive has potential in modulating the physicochemical properties of the film former to sustain drug release. This study reports the development and evaluation of DNA-incorporated HPMC film matrices to improve the ocular delivery and therapeutic efficacy of Diclofenac. Four formulations (DH1-DH4) were prepared with increasing DNA ratios (0, 1:0.01, 1:0.02, and 1:0.03). FTIR, DSC, and XRD analyses confirmed amorphous dispersion of Diclofenac within the matrix without chemical degradation, while SEM revealed a uniform and smooth film morphology. DNA incorporation significantly enhanced hydration (DH4: 620 ± 31.45%), transparency (DH4: ∼55% transmittance at 800 nm), and matrix erosion (DH4: 432 ± 30.25%), which contributed to improved drug release (DH4: 88.3 ± 2.6% at 300 min) and permeation (DH4: 89.5 ± 3.2% at 12 h). Kinetic modeling indicated a strong fit to the Higuchi model (R² = 0.95-0.99), while Korsmeyer-Peppas n values (0.37-0.52) suggested anomalous (non-Fickian) diffusion mechanisms. Stability studies confirmed high moisture retention (DH4: 96 ± 1.5%) and tensile strength (DH4: 20 ± 1.5 MPa) over three months, ensuring the formulation's shelf stability. Antioxidant assays demonstrated superior activity in DH4, with DPPH (IC₅₀: 32 ± 1.8 μM) and H₂O₂ scavenging (IC₅₀: 39 ± 1.7 μM). Overall, Diclofenac-DNA-HPMC films, particularly DH4, exhibit significant potential for effective ocular drug delivery by enhancing the therapeutic performance while maintaining stability and patient compliance.