Long-acting injectable nanoemulsion for anti-inflammatory therapy: luteolin and resveratrol-loaded CMC formulation regulates TH1/TH2 homeostasis in ovalbumin-induced allergic rhinitis in mice models

Allergic rhinitis (AR) continues to be a substantial global health concern, requiring the development of effective treatment methods. With an aim of enhancing medicine administration for the treatment of allergic rhinitis, the present work investigates the synthesis and characterization of a nanoemulsion consisting of luteolin (LTN) and resveratrol (RSV) encapsulated in carboxymethyl chitosan (CMC). Unlike traditional oral drugs, this formulation, upon nasal administration, avoids first-pass metabolism and achieves faster and stronger action. At various feed concentrations, LTN's and RSV's loading capacity was assessed to show optimal absorbance, mass of drug loading, and encapsulating efficiency. By means of their zeta potentials, particle size measurements indicated hydrated particle diameters of 215.3 ± 0.1 nm for LTN and 123.63 ± 0.1 nm for RSV, indicating appropriate stability. Functional groups and crystallinity in the formulations were confirmed by FTIR spectroscopy and X-ray diffraction. TEM and SEM morphological studies revealed spherical nanoemulsion droplets showing minimal aggregation. The highest encapsulation efficiencies were LTN at 96.75% and RSV at 97%. <i>In vitro</i> release experiments on the nanoemulsions showed far higher drug release rates compared with the raw materials. Based on biocompatibility testing, LTN/RSV@CMC exhibited minimal cytotoxicity and hemolysis rates of less than 5%. <i>In vivo</i> experiments using a mouse model of AR showed that administration of LTN/RSV@CMC substantially lowered allergy symptoms, histamine levels, cytokine production, and inflammatory cell-infiltration in NLF. The results reveal that LTN/RSV@CMC is a suitable therapeutic agent for AR, suppresses inflammatory responses, and has excellent safety characteristics.