Development of Quercetin-Loaded Polymeric Nanoparticle Based Thermosensitive In-Situ Gel for Ocular Drug Delivery

Background: Conventional eye drops don't stay on the ocular surface for long: blinking and tear turnover clear most of an instilled dose within minutes, and quercetin's poor aqueous solubility makes matters worse for any water-based formulation. A combined nanoparticle–thermosensitive in-situ gel approach was investigated here to address both limitations at once and provide sustained release. Objective: To develop and characterize quercetin-loaded polymeric nanoparticles carried within a thermosensitive ophthalmic in-situ gel — built from Moringa oleifera gum and Eudragit as particle-forming polymers, poloxamer 407 as the thermogelling agent, and polyvinylpyrrolidone K30 as a stabilizer — and to identify a lead formulation on the basis of its physicochemical profile and in-vitro release. Methods: Nine formulations (F1–F9) were prepared using Moringa gum alone, Eudragit alone, or the two combined, then evaluated in vitro. Release kinetics were further assessed against standard mathematical models. Results: The quercetin nanoparticle dispersion showed a mean particle size of 150.72 nm, a PDI of 0.174, and a zeta potential of +9.3 mV, with SEM confirming predominantly spherical, smooth particles. All nine formulations were clear and free-flowing, with pH values of 6.52–7.43. Gelation was rapid throughout the series — 32.0–33.9°C, taking 13.1–16.7 s. F8 gave the strongest overall performance: pH 7.43, viscosity of 31.3 cP at 2–8°C rising to 74.8 cP at 30–32°C, gelation at 32.1±0.2°C within 13.5 s, cumulative release of 49.47% at 8 h and 60.54% at 24 h, and the highest entrapped-drug concentration recorded, 3.46 µg/mL. Conclusion: The nanoparticle–thermosensitive gel system delivered favourable formulation-level characteristics, a rapid sol-to-gel transition near ocular temperature, and sustained in-vitro release of quercetin, with F8 identified as the lead formulation. Because the underlying study stopped short of animal experimentation, ocular safety, precorneal retention, bioavailability, and therapeutic efficacy remain open questions that will need controlled, ethically approved preclinical studies to answer.