In vitro and in vivo evaluation of DNA-integrated diclofenac–HPMC hydrogel for enhanced ocular anti-inflammatory drug delivery

Ocular inflammation is a major ophthalmic disorder associated with redness, irritation, pain, and tissue damage, requiring effective and sustained drug delivery for improved therapeutic management. The present study aimed to develop and evaluate diclofenac-loaded HPMC hydrogel (D-HG) and diclofenac–DNA–HPMC hydrogel (D-DNA-HG) for enhanced ocular anti-inflammatory therapy. The developed formulations exhibited ocular-compatible pH values of 7.11 ± 0.03 and 7.19 ± 0.02 for D-HG and D-DNA-HG, respectively. D-DNA-HG demonstrated higher drug content (89.45 ± 1.6%), improved spreadability (20.31 ± 0.4 g·cm/sec), and faster gelation behavior compared with D-HG. FTIR, XRD, and DSC studies confirmed successful incorporation of diclofenac and DNA into the HPMC hydrogel matrix with reduced crystallinity and enhanced intermolecular interactions. SEM and AFM analyses revealed compact and homogeneous morphology after DNA incorporation. D-DNA-HG showed enhanced transparency, superior rheological properties, sustained in-vitro drug release (98 ± 1.8% at 300 min), and improved ex-vivo permeation (98 ± 1.5% at 4 h). The formulation also exhibited strong antioxidant activity, excellent anti-inflammatory potential (93.8 ± 2.7%), minimal ocular irritation, and significant in-vivo therapeutic efficacy, indicating its potential as an advanced ocular drug delivery system.