Coaxial 3D-printed alginate-based pH-responsive hydrogels via in-situ crosslinking for curcumin delivery: Optimization of polysaccharide type and blending ratio

Abstract

This study aims to develop a coaxial 3D-printed core–shell delivery system, using a curcumin-loaded emulsion filled gel core, and a pH-responsive sodium alginate (SA) shell (SA-X-shell) enhanced with various polysaccharides (carboxymethyl cellulose (CMC), hydroxypropyl methyl cellulose (HPMC), and carboxymethyl chitosan (CMCS)) at varying ratios (3:1, 1:1, 1:3), to achieve targeted gastrointestinal delivery and controlled release of curcumin. Printing test found that in-situ cross-linking during printing between core Ca²⁺ and the SA-X-shell formed stable core–shell structures, and subsequent rheology tests confirmed their enhanced mechanical properties. FTIR and XRD analyses indicated that polysaccharide type and ratio both modulated intermolecular interactions and network structure within the SA-X-shell. In vitro simulated digestion showed that SA-, SA-CMC-, and SA-HPMC-coaxial samples sustained release with curcumin cumulative release below 60% within 8 h, whereas SA-CMCS-coaxial samples, particularly those with low SA content (S1CS1 and S1CS3), exhibited significantly higher release rates (89.38% and 91.90%, respectively). Complementary characterization via texture analysis, magnetic resonance imaging (MRI), and moisture distribution provided visual and quantitative insights into the swelling, disintegration, and release processes.

Industry relevance:

This study demonstrates that modulating the polysaccharide composition in SA-based hydrogels enables tunable control over their microstructure, mechanical strength, and pH-responsive release. These findings provide a scientifically grounded material strategy for designing intestine-targeted delivery systems that can enhance the stability, bioavailability, and targeted release of sensitive bioactives including probiotics, vitamins, and polyphenols, with direct applications in functional foods and nutraceuticals. Ultimately, it provides strategies for designing next-generation smart foods with customized efficacy and targeted health benefits.

Highlights

Introduction

Curcumin (CUR), a hydrophobic bioactive compounds (BCs) with diverse therapeutic properties, requires delivery systems that simultaneously ensure gastric protection, intestinal targeting, and enhanced bioavailability (Rauf, Imran, Orhan, & Bawazeer, 2018). While emulsion-based carriers have been widely explored to improve CUR loading stability and bioaccessibility (Araiza-Calahorra, Akhtar, & Sarkar, 2018; Sabet, Rashidinejad, Melton, & McGillivray, 2021), conventional single-layer emulsion gels lack multi-barrier protection due to their homogeneous interface and poor mechanical strength, causing CUR leakage, degradation, and structural failure during processing or gastrointestinal transit that compromises precision physiological targeting (Can Karaca et al., 2025; Zheng, Zhang, Chen, Luo, & McClements, 2017). To address these limitations, sodium alginate (SA) has gained attention for BCs delivery. SA combines the excellent biocompatibility and biodegradability common to natural polysaccharides (Rehman et al., 2020; Wang, Sun, & Mu, 2024; Yuan et al., 2023), with a unique molecular architecture comprising β-D-mannuronic acid (M) and α-L-guluronic acid (G) units, wherein the G blocks undergo specific ionic crosslinking with Ca2+ under mild conditions to form a stable “egg-box” structure (Hecht & Srebnik, 2016).This mechanism has been widely employed in conventional dripping methods to fabricate Ca2+-crosslinked SA-based hydrogel beads for encapsulating diverse BCs, including probiotics (Liu et al., 2024), peptides (Liu et al., 2025), vitamins (Kou, Wang, You, Wei, & Wu, 2024), and plant-derived BCs (e.g., fucoxanthin (Zhang et al., 2025)) as well as curcumin (Sun et al., 2025). Despite their widespread use, hydrogel beads are limited by structural inhomogeneity, geometric imprecision, poor release tunability, and an inability to achieve personalized design.

Compared to conventional single- and dual- 3D/4D printing(Feng, Zhang, Mujumdar, & Guo, 2024; Niu, Zhang, Mujumdar, & Li, 2026; Shi, Zhang, & Mujumdar, 2024; Tang, Zhang, Bhandari, & Li, 2024; Teng, Zhang, Adhikari, & Ma, 2024), coaxial food printing represents an advanced adaptation that employs independent channels to deliver core and shell inks that converge at a coaxial nozzle to form a concentric core–shell structure, which is subsequently deposited layer-by-layer to construct predefined models(Feng, Zhang, Mujumdar, Li, & Lin, 2025; Huang, Zhang, Mujumdar, & Li, 2025; Kong, Zhang, Mujumdar, Fan, & Li, 2025). The core-shell structure effectively encapsulates valuable BCs within the core, while the shell serves as a protective barrier (Lenie, Ahmadzadeh, Van Bockstaele, & Ubeyitogullari, 2024), demonstrating remarkable versatility as evidenced by its successful application in encapsulating curcumin (Jeon, Yu, Kim, & Park, 2021), lutein (Ahmadzadeh & Ubeyitogullari, 2023), phycocyanin (Park, Park, & Yu, 2024) and quercetin (Feng et al., 2025). Furthermore, coaxial 3D printing enables a one-step fabrication of core–shell structures through in-situ ionic (SA and Ca2+) crosslinking. As demonstrated by Truong-Le, Lenie, and Ubeyitogullari (2025), printing a SA–pectin shell with a Ca2+-loaded starch core simultaneously enhanced structural precision compared to conventional beads and preserved pH-responsive release. While coaxial printing offers potential for core-shell gels fabrication, how multi-component shell formulations regulate crosslinking and performance remain unclear. Studies show that blending polysaccharides with SA modulates gel network density and physicochemical properties (He et al., 2021; Jing et al., 2022). However, this regulatory mechanism has not been systematically investigated in coaxial printing, particularly regarding how shell composition influences Ca2+ migration during in-situ crosslinking to determine structural integrity and release behavior.

To address this gap, this study advances beyond prior work for CUR delivery by employing coaxial 3D printing to fabricate core–shell structures encapsulating CUR emulsion gels in one step. We hypothesize that the charge characteristics and ratio of polysaccharides blended with SA govern Ca2+-crosslinking kinetics and network density during coaxial printing, thereby modulating the pH-responsive behavior of printed shells during gastrointestinal transit. To test this, different charge characteristics of polysaccharides and blending ratio were selected. Also, direct correlations between shell composition, crosslinking density, structural evolution (swelling/disintegration), and CUR release rate were established through integrated rheology, FTIR, XRD, texture analysis, MRI, and in vitro digestion. This study elucidates composition-structure-function relationships, providing a theoretical and experimental basis for rationally designing core–shell delivery systems with spatiotemporally controlled release.

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Materials

Curcumin (CUR, Mw = 368.37 g/mol, 98%), Sodium alginate (SA, anionic), carboxymethyl cellulose (CMC, CAS: 9005-38-3, viscosity:500-1000mpa.s, anionic) were purchased from Titan Scientific Co., Ltd. (Shanghai, China). Hydroxypropyl methyl cellulose (HPMC, CAS: 9004-32-4, viscosity:1500-2800mpa.s, neutral), and carboxymethyl chitosan (CMCS, carboxyl substitution degree≥90%, CAS: 83512–85-0, cationic) were purchased from Meryer Biochemical Technology Co., Ltd. (Shanghai, China). Medium-chain…

Demei Kong, Min Zhang, Bhesh Bhandari, Dongcui Fan, Chunli Li, Coaxial 3D-printed alginate-based pH-responsive hydrogels via in-situ crosslinking for curcumin delivery: Optimization of polysaccharide type and blending ratio, Innovative Food Science & Emerging Technologies, Volume 113, 2026, 104717, ISSN 1466-8564, https://doi.org/10.1016/j.ifset.2026.104717.

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