DNA-Based Hybrid Hydrogels Sustain Water-Insoluble Ophthalmic Therapeutic Delivery against Allergic Conjunctivitis

Abstract

Clinical need for treating allergic conjunctivitis (AC) is rapidly increasing. However, AC-relevant anti-inflammatory compounds are generally difficult to solubilize in water, thus limiting their therapeutic potential. Solubility-improved eye drop formulations of these compounds have poor bioavailability and a short retention time in ophthalmic tissues. Herein, we report a DNA/poly­(lactic-co-glycolicacid) (PLGA) hybrid hydrogel (HDNA) for water-insoluble ophthalmic therapeutic delivery. PLGA pre-encapsulation enables loading of water-insoluble therapeutics. HDNA’s porous structure is capable of sustained delivery of therapeutics. Dexamethasone (DEX), with demonstrated activities in attenuating inflammatory symptom in AC, was used as a model system. The designed HDNA hybrid hydrogels significantly improved the DEX accumulation and mediated the gradual DEX release in ophthalmic cells and tissues. Using the HDNA–DEX complexes, potent efficacy in two animal models of AC was acquired. Given this performance, demonstrable biocompatibility, and biodegradability of DNA hydrogel, the HDNA-based ophthalmic therapeutic delivery system enables novel treatment paradigms, which will have widespread applications in the treatment of various eye diseases.

Distribution of serum specific IgE in children with allergic conjunctivitis and analysis of its concomitant allergic diseases

“…Some scholars have pointed out that the eye binding membrane is rich in blood vessels and exposed to external antigens, which can easily stimulate allergic symptoms (7). Allergens are affected by house dust, mites, fungi and other factors in different seasons, and there are many related studies on the increased positive expression of allergens.…”

New Developments in Medical Applications of Hybrid Hydrogels Containing Natural Polymers

“…The formation of these hybrid hydrogels was reversible [68]. A DNA/poly(lactic-co-glycolic acid) (PLGA) hybrid hydrogel (HDNA) was prepared for water-insoluble ophthalmic therapeutic delivery of dexamethasone and it may be applied in treatment of various eye diseases [69].…”

Recent Advances of DNA Hydrogels in Biomedical Applications

“…[69]), enabling a minimally invasive approach to local drug delivery. A hybrid hydrogel was developed to enhance the solubility of antiinflammatory compounds in water [70]. The pre-embedded DNA/poly(lactic-co-glycolic acid) can load water-insoluble therapeutic drugs (Fig.…”

“…1a in ref. [70]). The porous structure of DNA hydrogels enabled continuous delivery of therapeutic drugs to reduce the symptoms of allergic conjunctivitis.…”