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Vitiligo is a depigmenting autoimmune disease driven by oxidative stress and immune-mediated melanocyte destruction. Current therapies are limited by poor drug permeability, systemic side effects, and insufficient efficacy. Herein, we developed a novel carbomer-based hydroxypropyl-β-cyclodextrin-encapsulated crisaborole/curcumin hydrogel (Cri/Cur@CD-Gel) for combinational transdermal intervention of vitiligo via dual antioxidant and anti-inflammatory pathways. Hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexation overcame the inherent hydrophobicity of crisaborole (Cri) and curcumin (Cur), significantly enhancing their aqueous solubility, stability, and transdermal permeability. Leveraging its skin-adhesive properties, the carbomer hydrogel matrix enhanced drug retention and enabled sustained release at lesion sites, thereby improving drug bioavailability. In vitro , Cri/Cur@CD, leveraging the solubilizing power of HP-β-CD, restored melanocyte viability under oxidative stress, scavenged ROS, normalized mitochondrial membrane potential, and elevated cAMP levels to enhance melanogenesis and tyrosinase activity. In vivo , Cri/Cur@CD-Gel achieved significant repigmentation in monobenzone-induced vitiligo mice, markedly reducing epidermal ROS, CD8+ T-cell infiltration, and inflammatory cytokines (TNF-α, IL-1β, and IL-6). This study demonstrates that the combination of HP-β-CD-based encapsulation and carbomer hydrogel delivery serves as a potential topical administration platform for co-delivering hydrophobic crisaborole and curcumin, and establishes a promising strategy to alleviate vitiligo, that concurrently addresses oxidative damage, inflammatory responses, and melanocyte regeneration.
Purpose Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, −33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T 1/2 , MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.
The inefficient use of water-insoluble drugs is a major challenge in drug delivery systems. Core–sheath fibers with various shell thicknesses based on cellulose acetate (CA) were prepared by the modified triaxial electrospinning for the controlled and sustained release of the water-insoluble Chinese herbal active ingredient curcumin. The superficial morphology and internal structure of core–sheath fibers were optimized by increasing the flow rate of the middle working fluid. Although the prepared fibers were hydrophobic initially, the core–sheath structure endowed fibers with better water retention property than monolithic fibers. Core–sheath fibers had flatter sustained-release profiles than monolithic fibers, especially for thick shell layers, which had almost zero-order release for almost 60 h. The shell thickness and sustained release of drugs brought about a good antibacterial effect to materials. The control of flow rate during fiber preparation is directly related to the shell thickness of core–sheath fibers, and the shell thickness directly affects the controlled release of drugs. The fiber preparation strategy for the precise control of core–sheath structure in this work has remarkable potential for modifying water-insoluble drug release and improving its antibacterial performance.
In the context of critical challenges in curcumin-modified polyurethane synthesis—including limited curcumin bioavailability and suboptimal biodegradability/biocompatibility—a novel polyurethane material (Cur-PU) with good mechanical, shape memory, pH-responsive, and biocompatibility was synthesized via a one-pot, two-step synthetic protocol in which HO-PCL-OH served as the soft segment and curcumin was employed as the chain extender. The experimental results demonstrate that with the increase in Cur units, the crystallinity of the Cur-PU material decreases from 32.6% to 5.3% and that the intensities of the diffraction peaks at 2θ = 21.36°, 21.97°, and 23.72° in the XRD pattern gradually diminish. Concomitantly, tensile strength decreased from 35.5 MPa to 19.3 MPa, and Shore A hardness declined from 88 HA to 65 HA. These observations indicate that the sterically hindered benzene ring structure of Cur imposes restrictions on HO-PCL-OH crystallization, leading to lower crystallinity and retarded crystallization kinetics in Cur-PU. As a consequence, the material’s tensile strength and hardness are diminished. Except for the Cur-PU-3 sample, all other variants exhibited exceptional shape-memory functionality, with Rfand Rrexceeding 95%, as determined by three-point bending method. Analogous to pure curcumin solutions, Cur-PU solutions demonstrated pH-responsive chromatic transitions: upon addition of hydroxide ion (OH−) solutions at increasing concentrations, the solutions shifted from yellow-green to dark green and finally to orange-yellow, enabling sensitive pH detection across alkaline gradients. Hydrolytic degradation studies conducted over 15 weeks in air, UPW, and pH 6.0/8.0 phosphate buffer solutions revealed mass loss <2% for Cur-PU films. Surface morphological analysis showed progressive etching with the formation of micro-to-nano-scale pores, indicative of a surface-erosion degradation mechanism consistent with pure PCL. Biocompatibility assessments via L929 mouse fibroblast co-culture experiments demonstrated ≥90% cell viability after 72 h, while relative red blood cell hemolysis rates remained below 5%. Collectively, these findings establish Cur-PU as a biocompatible material with tunable mechanical properties, and pH responsiveness, underscoring its translational potential for biomedical applications such as drug delivery systems and tissue engineering scaffolds.
Sodium alginate (SA) gel beads are well-known carriers for curcumin (Cur) delivery, however their insufficient release efficiency in the colon restricts their application. To address this issue, we developed composite gel beads as Cur carriers, designated as PME-NPGP+SA, which comprised SA and pectin derived from Nicandra Physodes ( Linn. ) Gaertn. , modified with pectin methyl esterase. The encapsulation of Cur within PME-NPGP+SA gel beads was successful, achieving an encapsulation efficiency of 80.67 % and a retention rate of 87.20 % over a 10-day storage period. The incorporation of PME-NPGP fraction increased both the swelling rate and the colonic degradation of the SA-Cur gel beads without compromising their hardness. In subsequent in vitro digestion simulations, the composite gel beads showed an efficient colonic release rate of Cur at 49.98 %, outpacing the 28.93 % release rate of the SA gel beads. This study lays the foundation for the efficient colonic delivery of Cur.
In this study, the structural design and physicochemical property enhancement of undenatured type II collagen (UC-II) nanofibrils with sodium alginate (SA) coating induced by calcium ions (Ca 2+ ) were investigated. The research aimed to elucidate the impact of Ca 2+ concentration on the morphology, thermal stability , and digestive resistance, as well as to assess the potential of UC-II/SA nanofibrils as a delivery system for curcumin (Cur). A series of Ca 2+ concentrations (1–9 mM) were methodically applied to optimize the condition that maintains the triple-helical structure of UC-II, thereby enhancing its functional properties. It was found that the Ca 2+ level up to 5 mM effectively preserved the structural integrity and improved thermal stability of UC-II, with the added benefit of ensuring the substantial delivery of active fragment to small intestine (70.7 %), which was 3.43 times greater than that of uncoated UC-II. Moreover, incorporating Cur into the UC-II/SA nanofibrils resulted in a 300 times increase in Cur solubility and showcased the superior dispersion stability, antioxidant activity , and sustained release profile during simulated digestion. These findings underscored the dual functionality of the UC-II/SA system as both a stabilizing agent for UC-II nanofibrils and an efficient carrier for Cur delivery.
Background/Objectives:Triple-negative breast cancer (TNBC) exhibits pronounced biological heterogeneity, aggressive behavior, and a high risk of recurrence and metastasis. The conventional treatments for TNBC have notable limitations: surgical resection may leave residual tumor cells; chemotherapy (CT) frequently induces systemic toxicity and drug resistance; and radiotherapy damages surrounding organs and compromises the patients’ immune function.Methods: Herein, we designed a carrier-free nanodrug delivery system composed of self-assembled Curcumin nanoparticles (NPs) coated with a tannic acid (TA)/Fe(III) network (denoted as CUR@TA-Fe(III) NPs). We systematically evaluated the in vitro cytotoxicity and photothermal–ferroptosis synergistic therapeutic efficacy of CUR@TA-Fe(III) NPs in 4T1 breast cancer cells, as well as the in vivo antitumor activity using 4T1 tumor-bearing mouse models.Results:CUR@TA-Fe(III) NPs had high drug loading efficiency (LE) of 27.99%, good dispersion stability, and photothermal properties. Curcumin could inhibit the growth of 4T1 cancer cells, while TA-Fe(III) efficiently converted light energy into heat upon exposure to near-infrared (NIR) light, leading to direct thermal ablation of 4T1 cells. Additionally, TA-Fe(III) could supply Fe(II) via TA, increase intracellular Fe(II) content, and generate reactive oxygen species (ROS) through the Fenton reaction, in turn inducing lipid peroxidation (LPO), a decrease in mitochondrial membrane potential (MMP), and glutathione depletion, eventually triggering ferroptosis.Conclusions:This treatment strategy, which integrates CT, PTT, and ferroptosis, is expected to overcome the limitations of traditional single-treatment methods and provide a more effective method for the treatment of TNBC.
To improve the emulsifying property of sodium caseinate (NaCas) as stabilizer of oil-in-water emulsions and encapsulation of bioactive compounds, three hexaglycerol mono-fatty acid esters were chosen as small molecular weight surfactants to complex with NaCas. Hexaglycerol monooleate (HGMO) was found to be the optimal surfactant and the optimal mass ratio was 1:1, through characterization of particle size, Zeta-potential, and turbidity. Fluorescence and FTIR spectra indicated that the hydrophobic interaction and hydrogen bond provided driving forces to the formation of stable complex. The complexation of HGMO to NaCas increased the surface hydrophobicity and decreased surface tension compared with NaCas, and strengthened the EAI and ESI. The NaCas-HGMO complex had good stabilization on rice bran oil-in-water emulsions, in a wide pH and ionic strength, and the forwarding Cur encapsulation in O/W emulsions dramatically reduced the degradation during storage at 4℃. Therefore, the present NaCas-HGMO complex might be employed as an effective emulsifier to stable O/W emulsions that load lipophilic bioactives in functional foods or beverages.
The persistent challenges of multidrug resistance and systemic toxicity in cancer chemotherapy necessitate the development of intelligent, tumor-targeted co-delivery systems. Herein we report a novel nickel-based metal-organic framework (CUR + PTX@Ni-MOF) engineered with a phosphazene-derived ligand for the pH-responsive co-delivery of paclitaxel (PTX) and curcumin (CUR). The framework integrates a hexachlorocyclotriphosphazene (HCCP)-based linker featuring an intrinsically acid-labile P3N3 core enabling controlled degradation within the acidic tumor microenvironment (TME). The Ni-MOF exhibits a high BET surface area (177.118 m 2 /g) and a mesoporous architecture facilitating exceptional dual-drug loading capacities of 56.15% for CUR (96.3% encapsulation efficiency, EE) and 26.18% for PTX (43.01% EE). In vitro release studies demonstrated minimal drug leakage at physiological pH (7.4), while triggered, sustained release was achieved under acidic conditions (pH 6.5 and 5.0) with maximum cumulative releases of 75.42% for CUR and 49.35% for PTX at pH 5.0. Cellular assays confirmed high biocompatibility with normal LO2 hepatocytes (>80% viability) and potent, synergistic cytotoxicity against HeLa cancer cells driven by enhanced cellular uptake and apoptosis induction. This work establishes CUR + PTX@Ni-MOF as a promising, intrinsically pH-responsive platform for targeted and synergistic combination chemotherapy.
Achieving stable dispersion and sustained antibacterial activity of natural bioactive compounds in bio-based packaging remains challenging. In this study, chitosan (CS) films incorporating a β-cyclodextrin–curcumin inclusion complex (Cur/β-CD) were developed to improve film properties and the refrigerated preservation of sea bass. The CS/Cur/β-CD films were prepared by one-step solution casting without intermediate isolation or purification. The inclusion conditions were optimized, and the resulting films were evaluated in terms of tensile strength (TS), elongation at break (EAB), and water vapor permeability (WVP). Among the tested formulations, the film prepared at a Cur:β-CD ratio of 1:1, 40 °C, and 1 h (1:1 40 °C 1 h) showed the best overall performance in TS, EAB, and WVP. It was therefore selected for subsequent structural characterization, antibacterial evaluation, and preservation testing. The 1:1 40 °C 1 h film exhibited a 156% increase in tensile strength and a 28.5% decrease in water vapor permeability compared with the neat CS film. The composite film exhibited measurable diffusion-based antibacterial activity againstEscherichia coli(E. coli) andStaphylococcus aureus(S. aureus). During the 8 d refrigerated storage period, the film suppressed total viable counts (TVC), slowed the increase in pH, and retarded total volatile basic nitrogen (TVB-N) accumulation, thereby maintaining acceptable microbiological quality throughout the observation period. Compared with the unwrapped, PE, and CS-film control groups, the treated samples showed better preservation performance over the tested storage period. Overall, the incorporation of Cur/β-CD provides a simple strategy for improving the mechanical strength, moisture barrier properties, antibacterial activity, and preservation performance of CS films during refrigerated storage, highlighting their potential for active packaging of chilled aquatic products.
Diabetic chronic wounds are difficult to heal due to persistent inflammation, excessive oxidative stress, and high infection risk. Herein, a multifunctional GelMA-based microsphere co-loaded with silver ions and curcumin (GelMA-MS@Ag/Cur) was developed as an advanced wound dressing for diabetic wound repair. The porous GelMA microspheres enabled efficient encapsulation and sustained release of Ag + and curcumin while maintaining good biocompatibility and controlled degradation. GelMA-MS@Ag/Cur exhibited broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria and effectively reduced intracellular reactive oxygen species. The microspheres further promoted macrophage polarization toward the pro-regenerative M2 phenotype. Mechanistically, GelMA-MS@Ag/Cur regulated the KEAP1/Nrf2 signaling pathway and suppressed inflammation-induced ferroptosis by modulating ACSL4, SLC7A11, and GPX4 expression, thereby preserving cellular redox homeostasis. In a diabetic rat full-thickness wound model, GelMA-MS@Ag/Cur significantly accelerated wound closure, enhanced angiogenesis, collagen deposition, and tissue remodeling without observable systemic toxicity. This work provides a promising multifunctional strategy for diabetic chronic wound management.
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