Development of an isoquercitrin-loaded SNEDDS for enhanced oral absorption: a promising non-steroidal therapy for atopic dermatitis

Abstract

The oral bioavailability and therapeutic efficacy of a compound are largely determined by its aqueous solubility and interfacial partitioning. Isoquercitrin (IQC), a flavonoid with potent anti-inflammatory properties, has poor solubility and low interphase partitioning, limiting its absorption and systemic availability. To overcome these barriers, we developed a self-nanoemulsifying drug delivery system (SNEDDS) incorporating IQC (IQC-NE) to enhance its solubility and oral bioavailability.

Highlights

• A self-nanoemulsifying drug delivery system (SNEDDS) was developed for isoquercitrin (IQC)
• The optimized IQC-NE significantly enhanced solubility and oral bioavailability
• Oral IQC-NE reduced Th2 cytokines and IgE in an atopic dermatitis model
• IQC-NE suppressed immune cell infiltration and skin inflammation in vivo
• Oral IQC-NE showed potential as a non-steroidal therapy for atopic dermatitis

The optimized formulation (IQC-NE#9) consisted of 16.47% oil, 55.95% surfactant, and 28.23% co-surfactant, forming nano-sized emulsions upon contact with aqueous media. IQC-NE#9 enhanced lipid membrane fluidity, inhibited efflux transporters, and improved transcellular permeability, achieving a 17.0-fold increase in permeability across Caco-2/HT-29/MTX-E12 cell monolayers compared to free IQC. Pharmacokinetic studies in rats revealed a 15.1-fold improvement in oral bioavailability. In a 2,4-dinitrochlorobenzene-induced atopic dermatitis mouse model, oral administration of IQC-NE#9 significantly attenuated inflammation by reducing white blood cells, monocytes, neutrophils, eosinophils, lymphocytes, key cytokines (interleukin [IL]-4, IL-5, and IL-6), and immunoglobulin E.

These findings suggested that SNEDDS-based IQC delivery markedly enhances both bioavailability and anti-inflammatory efficacy, positioning IQC-NE#9 as a promising non-steroidal therapeutic candidate for atopic dermatitis.

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2.1. Materials

IQC (purity > 95%) was obtained from ChemFaces (Wuhan, China). Naringin (4′,5,7-trihydroxyflavonone-7-rhamnoglucoside) was used as an internal standard (IS) for IQC. Various excipients, including hydroxylated 12-hydroxy-9-octadecenoic acid (castor oil), (9Z)-octadec-9-enoic acid (oleic acid), polyethylene glycol 400 (PEG 400), polyoxyethylene (20) sorbitan monolaurate (Tween 20), polyoxyethylene (80) sorbitan monolaurate (Tween 80), sorbitan monolaurate (Span 80), sodium carboxymethyl cellulose (NaCMC), hydroxypropyl beta cyclodextrin (HP-beta-CD), sodium deoxycholate acid (NaDA), methyl beta cyclodextrin (M-beta-CD), dimethyl sulfoxide (DMSO), polyoxyl castor oil (Kolliphor RH40), polyoxyethylene (160) polyoxypropylene (30) glycol (Poloxamer 188), polyethylene-polypropylene glycol (407) (Kolliphor 407), n-dodecyl-β-d-maltoside (DDM), and polyethoxylated castor oil (Cremophor EL), were purchased from Sigma-Aldrich (St. Louis, MO, USA). Polyvinylpyrrolidone (Kollidon 90F) was obtained from BASF (Ludwigshafen, Germany). Additional lipid-based excipients, including caprylocaproyl macrogol-8-glycerides (Labrasol), diethylene glycol monoethyl ether (Transcutol HP), oleoyl polyoxylglycerides (Labrafil M 1944 CS), propylene glycol monocaprylate (Capryol 90), propylene glycol dicaprylocaprate (Labrafac PG), and polyglyceryl-6-dioleate (Plurol Oleique CC), were sourced from Gattefossé (Saint Priest, France). Essential culture media and reagents, including Dulbecco’s modified Eagle’s medium (DMEM), 1× non-essential amino acids, fetal bovine serum (FBS), and penicillin–streptomycin, were obtained from Cytiva (Logan, UT, USA). Hank’s balanced salt solution (HBSS) and phosphate-buffered saline (PBS) were purchased from Gibco (New York, NY, USA). Solvents of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and high-performance liquid chromatography (HPLC) grade were obtained from Reagents Duksan (Gyeonggi-do, Republic of Korea) and Thermo Fisher Scientific (Waltham, MA, USA). All chemical reagents used in the experiments were of analytical grade.

Susmita Phuyal, So-Hyeon Bok, Arjun Dhwoj Bamjan, Laxman Subedi, Mansingh Chaudhary, Nam Ah Kim, Seung-Sik Cho, Jung-Hyun Shim, Dae-Hun Park, Jin Woo Park, Development of an isoquercitrin-loaded SNEDDS for enhanced oral absorption: a promising non-steroidal therapy for atopic dermatitis, Journal of Drug Delivery Science and Technology, 2025, 107447, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2025.107447.

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