Solid lipid–threshold guided chitosan coating of NLCs for improved gastrointestinal stability and curcumin bioavailability

Abstract

Chitosan-coated nanostructured lipid carriers (CS-NLCs) were engineered to overcome the gastrointestinal instability and limited absorption of glycerol distearate (GDS)/medium-chain triglyceride (MCT)-based NLCs. Using a dropwise coating method, we systematically evaluated the impact of chitosan coating on digestive stability and intestinal permeability through in vitro digestion models, Ussing chamber assays, and confocal laser scanning microscopy (CLSM).

Highlights

Glycerol distearate and medium chain triglyceride based NLC was coated with chitosan.

Chitosan coating affected digestive stability by altering flocculation dynamics.

Chitosan coating led to faster initial digestion rate and prolonged the release of curcumin.

Ussing Chamber showed a decrease in intestinal permeability due to chitosan coating.

Chitosan coating improved permeability in NLC with solid lipid content reached 80 %.

The results indicate that Chitosan coating improved NLCs’ storage stability (except G2M8 formulation). CS-NLCs exhibited more complete digestion (the maximum fatty acid released within 20 min versus 30 min for uncoated NLCs), with Turbiscan analysis demonstrating an increase in initial digestion rate compared to uncoated NLCs, though chitosan-induced flocculation reduced small intestinal permeability (52 % lower apparent permeability coefficient in Ussing chambers).

CLSM imaging identified a critical solid lipid threshold (>50 %) for chitosan-mediated adhesion enhancement, with 80 % solid lipid CS-NLCs showing 1.6-fold higher mucus adhesion due to incomplete chitosan degradation and increased particle size (from 747 nm to 16μm). Pharmacokinetic studies in rats confirmed that CS-NLCs with > 50 % solid lipid achieved 1.8-fold higher curcumin bioavailability versus uncoated counterparts. This study highlights the critical role of chitosan coating in optimizing the bioavailability of lipid-based nutraceuticals in the gastrointestinal tract.

Materials

Chitosan (degree of deacetylation ≥ 95 %; viscosity, 100–200 mpa·s; Mw 150–300 kDa) and curcumin (≥ 98 %) were purchased from Macklin (Shanghai, China). Medium chain triglyceride (MCT), Nile Red, Lecithin and Sodium bovine deoxycholate were purchased from Source Leaf Biotechnology (Shanghai, China). Glycerol distearate (GDS; melting temperature, 72–74 ℃) was purchased from Weng Jiang Chemical Reagent (Guangdong, China), while Tween 80 was obtained from Yongda Chemical Reagent (Tianjin, China).

Chujing Wang, Zengliu Song, Xinyue Ning, Yong Wang, Jie Xiao, Solid lipid–threshold guided chitosan coating of NLCs for improved gastrointestinal stability and curcumin bioavailability, Colloids and Surfaces A: Physicochemical and Engineering Aspects, Volume 723, 2025, 137388, ISSN 0927-7757, https://doi.org/10.1016/j.colsurfa.2025.137388.