Hesperidin-Loaded Lipid Polymer Hybrid Nanoparticles for Topical Delivery of Bioactive Drugs

Abstract

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.

In vitro–in vivo assessments of apocynin-hybrid nanoparticle-based gel as an effective nanophytomedicine for treatment of rheumatoid arthritis

“…Furthermore, the disappearance of APO’s peaks was discerned in the thermography of medicated hybrid NPs suggesting a felicitous encapsulation process inside the hybrid lipid-polymer matrix, concomitant with crystallinity disruption of pure APO. Present data substantiate the FT-IR outcomes and coincide with previously reported ones [ 19 , 21 , 22 ].…”

“…Hybrid nanoparticles (NPs) are the newest generation delivery systems that integrate lipid-based and polymeric nanocarriers and combine the benefits rendered by both, which allow incorporation of hydrophilic as well as hydrophobic drugs and improve drug stability besides efficacy [ 19 – 22 ].…”

Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases

“…They were, for example, inclusion complex with cyclodextrin [ 24 ], phospholipid complex [ 25 ], nanoemulsions [ 26 ], nanophytosomes [ 27 ], solid dispersion [ 28 , 29 ], and nanodispersion [ 30 ]. Hesperidin delivery systems have also been confirmed with chitooligosaccharide by spray drying [ 31 ], gold nanoparticles by a chemical synthesis method [ 32 ], chitosan nanoparticles [ 33 ], and lipid–polymer hybrid nanoparticles by the emulsification solvent evaporation method [ 34 ]. For example, Stanisic et al [ 26 ] obtained hesperidin with an approximate purity of 98% from orange pomace by aqueous extraction.…”

Development of a Novel Methotrexate-Loaded Nanoemulsion for Rheumatoid Arthritis Treatment with Site-Specific Targeting Subcutaneous Delivery

“…The different thermal peak of methotrexate and the nanoemulsion justifies that the drug is in an amorphous state. Moreover, as the temperature increases, there is an interaction between methotrexate and oil, which forms a complex that has a lower melting point (82.57 °C) than pure methotrexate [29,30]. The TEM (transmission electron microscopy) image of methotrexate-loaded nanoemulsion shows a particle size of less than 100 nm with a spherical shape (Figure 5).…”

“…The different thermal peak of methotrexate and the nanoemulsion justifies that the drug is in an amorphous state. Moreover, as the temperature increases, there is an interaction between methotrexate and oil, which forms a complex that has a lower melting point (82.57 • C) than pure methotrexate [29,30].…”