| Summary: | Hesperidin is a bioflavonoid constituent that among many other biological activities shows significant wound healing properties. However, the bioavailability of hesperidin when applied topically is limited due to its low solubility and systemic absorption, so novel dosage forms are needed to improve its therapeutic efficacy. The objectives of this study were to develop hesperidin-loaded lipid-polymer hybrid nanoparticles (HLPHNs) to enhance the delivery of hesperidin to endogenous sites in the wound bed and promote the efficacy of hesperidin. HLPHNs were optimized by response surface methodology (RSM) using the Box-Behnken design. HLPHNs were prepared using an emulsion-solvent evaporation method based on a double emulsion of water-in-oil-in-water (w/o/w) followed by freeze-drying to obtain nanoparticles. The prepared formulations were characterized using various evaluation parameters. In addition, the antioxidant activity of HLPHN 4 was investigated in vitro using the DPPH model. Seventeen different HLPHNs were prepared and the HLPHN4 exhibited the best mean particle size distribution, zeta potential, drug release and entrapment efficiency. The values are 91.43 nm, +23 mV, 79.97% and 92.8%, respectively. Transmission electron microscope showed similar spherical morphology as HLPHN4. Differential scanning calorimetry verified the physical stability of the loaded drug in a hybrid system. In vitro release studies showed uniform release of the drug over 24 h. HLPHN4 showed potent antioxidant activity in vitro in the DPPH model. The results of this study suggest that HLPHNs can achieve sustained release of the drug at the wound site and exhibit potent in vitro antioxidant activity.
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