Co-delivery of chemotherapeutic agents and proteins for cancer therapy faces multiple formulation challenges, including poor drug solubility, protein instability, and limitations of carrier systems. To address these issues, the authors developed a multifunctional, stimuli-responsive polymer hydrogel designed for localized delivery in breast cancer. The approach integrates a biocompatible ionic liquid into a polymeric matrix to improve loading, stability, and controlled release of both small-molecule and protein therapeutics.
The hydrogel is an interpenetrating polymer network composed of sodium alginate (SA) and polyvinyl alcohol (PVA) with incorporation of the biocompatible ionic liquid choline-lineolate ([Cho][Lin]). The system was loaded with the chemotherapeutic doxorubicin (DOX) and the model protein zein for co-delivery. The authors selected the ionic liquid to enhance solubility and stability of encapsulated agents and to establish noncovalent interactions within the polymer matrix that support multifunctional behavior.
Small-angle neutron scattering (SANS) was used to examine the aggregation behavior of the ionic liquid within the hydrogel and provided evidence supporting the solubility and stability of DOX and zein in the network. Fourier-transform infrared spectroscopy (FTIR) identified noncovalent interactions between the ionic liquid and the polymer components, consistent with an integrated matrix architecture. Circular dichroism (CD) analysis demonstrated that the protein structural integrity of zein was preserved after incorporation into the hydrogel, indicating that the formulation process did not denature the loaded protein according to the reported measurements.
Field-emission scanning electron microscopy (FE-SEM) revealed a well-defined, porous three-dimensional network with elongated fibrillar structures. This morphology is consistent with an interpenetrating polymer hydrogel capable of accommodating both drug and protein cargo.
Rheological analysis characterized the mechanical behavior of the hydrogel. The material exhibited viscoelasticity, shear-thinning behavior, and a reported mechanical stability with a critical strain (γc) of 100% strain. These mechanical properties support deformation under shear (for injection) and recovery in the absence of applied stress.
Based on the rheological profile and the polymer–ionic liquid interactions, the authors report that the hydrogel demonstrates injectability, self-healing capability, and strong adhesion. These functional attributes are intended to enable minimally invasive administration, retention at a local site, and recovery of the gel network after mechanical disruption — properties relevant for localized cancer therapy applications.
Biocompatibility testing on HaCaT human keratinocyte cells showed high cell viability after exposure to the hydrogel in vitro. Specifically, viability exceeded 92% after 48 hours, indicating low cytotoxicity of the carrier matrix itself under the reported experimental conditions.
Drug and protein release studies demonstrated pH-responsive behavior of the hydrogel system. Under acidic conditions — designed to model the tumor microenvironment — release of the encapsulated agents was substantially higher than at neutral pH. Reported release fractions under acidic conditions were approximately 89% for doxorubicin and 80% for zein. This pH-dependent release profile supports the concept of enhanced payload delivery within acidic tumor sites relative to normal physiological pH.
Cytotoxicity assays performed with MCF-7 breast cancer cells showed that the drug-loaded hydrogel produced an IC50 value of approximately 2 μM. This result indicates that the hydrogel formulation delivers therapeutically active concentrations of doxorubicin to achieve cancer cell kill in vitro under the reported assay conditions.
The authors conclude that an ionic liquid–based interpenetrating SA/PVA hydrogel can function as a versatile platform for co-delivery of small-molecule chemotherapeutics and proteins. The reported advantages include preserved protein structure, enhanced solubility/stability of cargo, pH-responsive release favoring acidic tumor-like environments, injectability, self-healing, and low carrier cytotoxicity in vitro. These features support further investigation of such hydrogels as localized delivery systems in breast cancer therapy.
Limitations and reporting scope: the available summary reports the experimental techniques and principal in vitro outcomes (viability on HaCaT, release fractions, and MCF-7 IC50) but does not provide detailed protocols, in vivo data, long-term stability results, or comprehensive safety assessments within the abstract. Those details were not reported in the source abstract and would need to be consulted in the full text for translational evaluation.