Delivery Of Curcumin Research Articles

Characterization of ultrasound-assisted covalent binding interaction between β-lactoglobulin and dicaffeoylquinic acid: Great potential for the curcumin delivery

The low bioavailability and poor gastrointestinal instability of curcumin hampers its application in pharmaceutical and food industries. Thus, it is essential to explore efficient carrier (e.g. a combination of polyphenols and proteins) for food systems. In this study, covalent β-lactoglobulin (LG)-dicaffeoylquinic acids (DCQAs) complexes were prepared by combining ultrasound and free radical induction methods. Covalent interactions between LG and DCQAs were confirmed by analyzing reactive groups. Variations in secondary or tertiary structure and potential binding sites of covalent complexes were explored using Fourier transform infrared spectroscopy and circular dichroism. Results showed that the β-sheet content decreased and the unordered content increased significantly (P < 0.05). The embedding rate of curcumin in prepared LG-DCQAs complexes using ultrasound could reach 49 % − 62 %, proving that complexes could embed curcumin effectively. This study highlights the benefit of ultrasound application in fabrication of protein–polyphenol complexes for delivering curcumin.

Curcumin for Treating Breast Cancer: A Review of Molecular Mechanisms, Combinations with Anticancer Drugs, and Nanosystems.

Breast cancer (BC) has become the fifth most prevalent cause of cancer-related morbidity, attracting significant attention from researchers due to its heightened malignancy and drug resistance. Conventional chemotherapy approaches have proven inadequate in addressing all BC subtypes, highlighting the urgent need for novel therapeutic approaches or drugs. Curcumin (CUR), a phytochemical derived from Curcuma longa (turmeric), has shown substantial potential in inhibiting BC cell migration, metastasis, and proliferation. However, the use of CUR in this context comes with challenges due to its dynamic and easily degradable nature, poor aqueous solubility, low bioavailability, rapid metabolism, and swift systemic elimination, collectively limiting its clinical applications. As such, we provide an overview of the properties, synthesis, and characterization of the hybridization of CUR and its analogue with chemo-drug building blocks. We reviewed research from the last five years on CUR's biogenesis with respect to the regulation of BC, revealing that CUR participates in arresting BC cells in the cell cycle and significantly induces apoptosis in BC cells. Information on the chemotherapeutic and antitumor mechanisms of CUR in BC, including regulation of the cell cycle, increased cell apoptosis, and inhibition of multidrug resistance (MDR), was compiled. Additionally, we provide an overview of CUR loaded into nanomaterials that are cotreated with other chemotherapeutic drugs, such as paclitaxel, thymoquinone, and tamoxifen. In this review, we discuss different types of nanoparticles that can be used for CUR delivery, such as polymeric nanoparticles, carbon nanotubes, and liposomes. By comparing the size, entrapment efficiency, drug-loading capacity, release time, biocompatibility, pharmaceutical scale, and reproducibility of various nanomaterials, we aimed to determine which formulations are better suited for loading CUR or its analogue. Ultimately, this review is expected to offer inspiring ideas, promising strategies, and potential pathways for developing advanced anti-BC strategy nanosystems in clinical practice.

Nanocrystal Agglomerates of Curcumin Prepared by Electrospray Drying as an Excipient-Free Dry Powder for Inhalation.

Curcumin has shown beneficial effects on pulmonary diseases with chronic inflammation or abnormal inflammatory responses, including chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. Clinical applications of curcumin are limited due to its chemical instability in solution, low water solubility, poor oral bioavailability, and intestinal and liver first-pass metabolism. Pulmonary delivery of curcumin can address these challenges and provide a high concentration in lung tissues. The purpose of the current work was to prepare a novel inhalable dry powder of curcumin nanocrystals without added excipients using electrospray drying (ED) with improved dissolution and aerosolization properties. ED of curcumin was performed at 2 and 4% w/v concentrations in acetone. Physicochemical properties of the formulated powders were evaluated by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), density and powder flow measurements, and in vitro dissolution. The in vitro deposition studies were conducted using next-generation impactor (NGI) and aerosol performance and aerodynamic particle size parameters were calculated for prepared formulations. ED could produce agglomerates of nanocrystals with a size of about 500 nm at an acceptable yield of about 50%. PXRD and FTIR data revealed that prepared nanocrystals were in a stable crystalline state. The bulk and tapped density of prepared agglomerates were in the range appropriate for pulmonary delivery. Formed nanocrystals could significantly improve the dissolution rate of water-insoluble curcumin. The optimized formulation exhibited acceptable recovered dose percentage, high emitted dose percentage, optimum mean mass median aerodynamic diameter, small geometric standard deviation, and high fine-particle fraction that favors delivery of curcumin to the deep lung regions. The ED proved to be an efficient technique to prepare curcumin nanocrystals for pulmonary delivery in a single step, at a mild condition, and with no surfactant.

Curcumin, its derivatives, and their nanoformulations: Revolutionizing cancer treatment.

Curcumin is a natural compound derived from turmeric and can target malignant tumor molecules involved in cancer propagation. It has potent antioxidant activity, but its effectiveness is limited due to poor absorption and rapid elimination from the body. Various curcumin derivatives have also shown anticancer potential in in-vitro and in-vivo models. Curcumin can target multiple signaling pathways involved in cancer development/progression or induce cancer cell death through apoptosis. In addition, curcumin and its derivatives could also enhance the effectiveness of conventional chemotherapy, radiation therapy and reduce their associated side effects. Lately, nanoparticle-based delivery systems are being developed/explored to overcome the challenges associated with curcumin's delivery, increasing its overall efficacy. The use of an imaging system to track these formulations could also give beneficial information about the bioavailability and distribution of the nano-curcumin complex. In conclusion, curcumin holds significant promise in the fight against cancer, especially in its nanoform, and could provide precise delivery to cancer cells without affecting normal healthy cells.

Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma.

Given the numerous adverse effects of lung cancer treatment, more research on non-toxic medications is urgently needed. Curcumin (CUR) and berberine (BBR) combat drug resistance by controlling the expression of multidrug resistant pump (MDR1). Fascinatingly, combining these medications increases the effectiveness of preventing lung cancer. Their low solubility and poor stability, however, restrict their therapeutic efficacy. Because of the improved bioavailability and increased encapsulation effectiveness of water-insoluble medicines, surfactant-based nanovesicles have recently received a great deal of attention. The current study sought to elucidate the Combination drug therapy by herbal nanomedicine prevent multidrug resistance protein 1: promote apoptosis in Lung Carcinoma. The impact of several tween (20, 60, and 80) types with varied hydrophobic tails on BBR/CUR-TNV was evaluated. Additionally, the MDR1 activity and apoptosis rate of the BBR/CUR-TNV combination therapy were assessed. The encapsulation effectiveness of TNV was affected by the type of tween. With the TNV made from tween 60, cholesterol, and PEG (47.5: 47.5:5), more encapsulation effectiveness was attained. By combining CUR with BBR, especially when given in TNV, apoptosis increased. Additionally, when CUR and BBR were administered in combination, they significantly reduced the risk of MDR1 development. The current work suggests that the delivery of berberine and curcumin as a combination medication therapy via tween-based nanovesicles may be a potential lung cancer treatment.

Scallop hydrolysates/κ-carrageenan hydrogels improve the alleviating effect of curcumin on DSS-induced colitis

Scallop (Patinopecten yessoensis) male gonad hydrolysates/κ-carrageenan (SK) double cross-linking network hydrogels were constructed as curcumin (Cur) delivery vehicles with good gel mechanical property and homogeneous honeycomb microstructures. Compared with Cur + DSS group, weight loss and colon length in SK-Cur + DSS group increased about 1.04 and 1.06 folds, while the disease active index (DAI) scores decreased about 13 %. Moreover, SK-Cur showed superior effect on intestinal barrier improvement, oxidative stress modulation, and inflammatory expression regulation, reflected by 1.1 folds increment of epithelial tight junction proteins, 16 % and 27 % decline in MPO and iNOS levels, 20 % decline in NF-κB expression, 4 %, 7 %, 6 % decline in TNF-α, IL-1β, IL-6 expression in serum, and 9 %, 20 %, 7 % decline in TNF-α, IL-1β, IL-6 expression in colon tissue. Furthermore, SK-Cur enriched alpha diversity and restored taxonomic composition with increasing Bacteroides and Verrucomicrobia abundance accompanied by decreasing Firmicutes in DSS-induced UC mice, roughly to a normal gut flora state.

Strategies to enhance oral delivery of curcumin using solid self-emulsifying drug delivery systems

Strategies to enhance oral delivery of curcumin using solid self-emulsifying drug delivery systems

New metal-organic framework coated sodium alginate for the delivery of curcumin as a sustainable drug delivery and cancer therapy system

The utilization of biocompatible drug delivery systems with extended drug release capabilities is highly advantageous in cancer therapy, as they can mitigate adverse effects. To establish such a biocompatible system with prolonged drug release behavior, researchers developed an innovative drug carrier. In this study, a sustainable approach was employed to synthesize a new zinc-based metal-organic framework (Zn-MOF) through the reaction between synthesized Schiff base ligands and zinc ions. Comprehensive analyses, including FT-IR, XRD, SEM, BET surface area, and TGA techniques, were employed to thoroughly characterize the frameworks. Following comprehensive characterization, curcumin (CUR) was loaded onto the Zn-MOF, resulting in CUR entrapment efficiency and loading capacity of 79.23 % and 26.11 %, respectively. In vitro evaluations of CUR release from CUR@MOF exhibited controlled release patterns, releasing 78.9 % and 50.0 % of CUR at pH 5.0 and pH 7.4, respectively. To mitigate initial burst release, a coating of the biopolymer sodium alginate (SA) was applied to CUR@Zn-MOF. In vitro CUR release tests indicated that SA/CUR@Zn-MOF outperformed pristine CUR@Zn-MOF. The release of CUR conformed to the Korsmeyer-Peppas model, displaying non-Fickian diffusion. Furthermore, an in vitro cytotoxicity study clearly demonstrated the potent anti-tumor activity of the synthesized CUR@Zn-MOF attributed to its controlled release of CUR. This led to the induction of apoptotic effects and cell death across HeLa, HEK293, and SH-SY5Y cell lines. These findings strongly suggest that the developed pH-sensitive carriers hold remarkable potential as targeted vehicles for drug delivery in cancer therapy.

Effects of the Herbal Product Curcumin on Cardiomyocytes in Micromass Culture and the Potential Role It May Play in Pregnancy and Development.

Introduction Herbal medicine (HM) consumption during pregnancy has been on the rise in many parts of the world. Curcumin is a proven antioxidant and anti-inflammatory herb component, having demonstrated efficacy in alleviating various diseases. However, there is conflicting evidence with regards to its effect on pregnancy. We assess the safety profile of the main component of turmeric, curcumin, during pregnancy. Furthermore, to investigate curcumin in combination with known teratogen ethanol to identify any protective effect that curcumin might exert. Method Embryonic chick cardiomyocytes in micromass culture were treated with varying concentrations of curcumin. Three endpoints were used to determine the effect of curcumin on these cells: contractile activity (morphological score), cell viability (resazurin assay), and total protein content (kenacid blue assay). Results Curcumin demonstrated cytotoxicity at the highest tested concentrations (10-20μM)by significantly reducing cell activity and total protein. The results of morphological scoring suggest that repeated investigations would have revealed the teratogenic potential of curcumin. Lower concentrations (50nM) of curcumin were comparable to the control. The combination of a non-toxic concentration of curcuminwith ethanol revealed additive toxicity. Conclusion It seems unlikely that curcumin will adversely affect the embryo at low doses due to issues of bioavailability. The findings of cytotoxicity and possible teratogenicity at high concentrations are a concern. Due to the limited information available regarding curcumin metabolism in human embryos, advancements in curcumin delivery systems, and the high likelihood of overconsumption, further in vivo research using animal models is required.

Pectin-coated whey protein isolate/zein self-aggregated nanoparticles as curcumin delivery vehicles: Effects of heating, pH, and adding sequence

In this work, pectin was employed as a coating material to fabricate zein/whey protein isolate (WPI)/pectin complex nanoparticles via a pH-adjusted and heat-induced electrostatic adsorption process for potential oral administration applications of curcumin. Factors such as the order of raw material addition, heating temperature and pH, and zein concentration were comprehensively examined. In addition to electrostatic interactions, Fourier transform infrared and fluorescence spectroscopy indicated that hydrophobic interactions and hydrogen bonds were also involved in the development of complex nanoparticles. The complex nanoparticles obtained not only improved the antioxidant activity of curcumin in aqueous phase, but also contributed to its controlled release under gastrointestinal conditions. Our findings revealed that the heating pH and adding sequence of raw materials had a notable impact on the properties of complex nanoparticles, and that pectin coating had an exceptional stabilizing effect on complex nanoparticles under gastrointestinal circumstances. This study provides novel insights and perspectives for the preparation of polysaccharide-protein complex nanoparticles, signifying the potential use of zein/WPI/pectin complex nanoparticles as delivery vehicles in the functional food and pharmaceutical industries.

Co-encapsulation of curcumin and anthocyanins in bovine serum album-fucoidan nanocomplex with a two-steppH-driven method.

Curcumin (CUR) and anthocyanins (ACN) are recommended due to their bioactivities. However, their nutritional values and health benefits are limited by their low oral bioavailability. The incorporation of bioactive substances into polysaccharide-protein composite nanoparticles is an effective way to enhance their bioavailability. Accordingly, this study explored the fabrication of bovine serum albumin (BSA)-fucoidan (FUC) hybrid nanoparticles using a two-step pH-driven method for the delivery of CUR and ACN. Under a 1:1 weight ratio of BSA to FUC, the point of zero charge moved from pH ⁓ 4.7 for BSA to around 2.5 for FUC-coated BSA, and the formation of BSA-FUC nanocomplex was pH-dependent by showing the maximum CUR emission wavelength shifting from 546 nm (CUR-loaded BSA-FUC at pH 4.7) and 544 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 4.7) to 540 nm (CUR-loaded BSA-FUC at pH 6.0) and 539 nm (CUR/ACN-loaded BSA-FUC nanoparticles at pH 6.0). Elevated concentrations of NaCl from 0 to 2.5 mol L-1 caused particle size increase from about 250 to about 800 nm, but showing no effect on the encapsulation efficiency of CUR. The CUR and ACN entrapped, respectively, in the inner and outer regions of the BSA-FUC nanocomplex were released at different rates. After incubation for 10 h, more than 80% of ACN was released, while less than 25% of CUR diffused into the receiving medium, which fitted well to Logistic and Weibull models. In summary, the BSA-FUC nanocomposites produced by a two-step pH-driven method could be used for the co-delivery of hydrophilic and hydrophobic nutraceuticals. © 2023 Society of Chemical Industry.

Elucidating pH dynamics in Pickering emulsions stabilized by soybean protein isolate and nicotinamide mononucleotide: Enhancing emulsification and curcumin delivery mechanisms

This research investigates the intricate dynamics of fish oil Pickering emulsions emulsified by soybean protein isolate/nicotinamide mononucleotide (SPI/NMN) under varying pH conditions and curcumin (CUR) concentrations. The study reveals that the droplet size distribution of the emulsion attains its minimum at a CUR concentration of 0.5 wt%, attributed to optimal interfacial interactions between CUR and SPI/NMN. Beyond this concentration, droplet size distribution increases due to potential droplet aggregation. In the realm of drug encapsulation, the encapsulation efficiency of CUR peaks at 87% at this concentration, underscoring the need for a balance between drug load and encapsulation efficiency. Notably, pH significantly affects emulsion stability, with optimal stability achieved at pH∼9. Under acidic conditions, the emulsion is less stable, with CUR adopting an open enolic tautomeric conformation that enhances its binding behavior. The release of CUR from the emulsions is modulated by pH, exhibiting a 92% release at pH∼2 over 16 h, in contrast to a 60% release in the pH 5–9 range. The findings provide crucial insights into the behavior and stability of SPI/NMN emulsified systems, offering potential applications in drug delivery system design. The use of SPI/NMN complex for stabilizing Pickering emulsions presents an advanced approach to enhancing emulsion stability. Precise control over drug release is attainable through pH modulation, providing substantial benefits in terms of improved drug efficacy, reduced side effects, and augmented patient convenience.

Stability and gastrointestinal behavior of curcumin-loaded emulsion stabilized by multi-conformation soy proteins: Influence of oil volume fraction

The aim of this work was to assess the potential of nanoemulsions stabilized by mixed soy protein with multi-conformation as curcumin carrier, and the influence of oil volume fraction on stability and gastrointestinal behavior of curcumin-loaded emulsion was investigated. Loading efficiency showed a slight increase with higher oil content, though the difference was not statistically significant. With the increase of oil, the viscosity (Pa‧s), thixotropy (area of hysteresis loop) and particle size of the emulsion increased, which facilitated the physical and chemical stability of curcumin-loaded emulsion. However, the free fatty acid release rate and bioaccessibility of curcumin was negatively correlated with the oil volume fraction and the particle size of emulsion after gastric digestion. Notably, the digestion in stomach did not affect the structure of interfacial protein, demonstrating that protein-based nanoemulsions exhibited resistance to gastric digestion. This study provides theoretical guidance for the application of protein-based emulsion in curcumin delivery.

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

Citrus peel pectin and alginate-based emulgel particles for small intestine-targeted oral delivery of curcumin

Polysaccharides are a prominent choice in the realm of food-grade oral delivery systems due to their resistance to degradation by digestive enzymes in the oral, gastric, and small intestinal environments, as well as their ease of production, cost-effectiveness, and potential health benefits as prebiotics. Furthermore, their ability to respond to pH-induced dissolution, along with their emulsifying properties, can be strategically employed to achieve precise targeting of lipophilic bioactives to the small intestine. In this study, citrus peel pectin and alginate served as stabilizers for emulgel particles without supplementary emulsifiers or gelling agents. Within this system, pectin functioned as an emulsifier, while alginate acted as a gelling agent, facilitated by Ca2+-induced ionic crosslinking. The synergistic interplay between pectin and alginate efficiently protected curcumin in gastric conditions and controlled dissolution in the small intestine, depending on the pectin/alginate ratio. These controlled phenomena facilitated lipolysis, curcumin release, and ultimately enhanced curcumin bioaccessibility. Furthermore, once the emulgel particle released all the entrapped curcumin in the small intestine, residual polysaccharides underwent facile degradation by pectinase and alginate lyase, yielding fermentable monosaccharides. This confirms the potential of the emulgel particles for use as a prebiotic in the colon. These findings offer significant promise for enhancing the systematic design of food-grade delivery systems that encapsulate lipophilic bioactives, achieving controlled release, enhanced stability, and improved bioaccessibility. Importantly, this system can comprise components that undergo complete digestion, absorption, and utilization in the human body, encompassing materials such as oil, nutraceuticals, and prebiotics, all without presenting health risks.

COMPLEXATION OF CURCUMIN WITH BOVINE SERUM ALBUMIN AND DIPHTHERIA TOXOID CRM197

Aim. The goal of the study is to demonstrate the binding sites for curcumin on the protein carriers - bovine serum albumin and diphtheria toxoid CRM197. BSA was chosen as a potential non-specific protein carrier because of its widely used in medicine as a drug carrier. Methods. In the investigation, both spectrophotometric and molecular docking methods were used. Results. Two stable binding sites were demonstrated for BSA to bind curcumin. CRM197 was taken as a well-studied carrier protein with its own antitumor activity and has been investigated as a specific carrier with a high affinity for cancer cells with overexpression of epidermal growth factor receptor. Our results showed one possible curcumin binding site, making CRM197 an ideal specific curcumin delivery platform that provides at least an additive effect in anticancer therapies. Conclusions. In conclusion, both studied proteins form stable complexes with curcumin that can lay in base of the commercial drug application.

Glycation-induced enhancement of yeast cell protein for improved stability and curcumin delivery in Pickering high internal phase emulsions

Pickering high internal phase emulsions (HIPEs) have gained significant attention for various applications within the food industry. Yeast cell protein (YCP), derived from spent brewer's yeast, stands out as a preferred stabilizing agent due to its cost-effectiveness, abundance, and safety profile. However, challenges persist in utilizing YCP, notably its instability under high salt concentration, thermal processing, and proximity to its isoelectric point. This study aimed to enhance YCP's emulsifying properties through glycation with glucose and evaluate its efficacy as a stabilizer for curcumin (CUR)-loaded HIPEs. The results revealed that glycation increased YCP's surface hydrophobicity, exposing hydrophobic groups. This augmentation, along with steric hindrance from grafted glucose molecules, improved emulsifying properties, resulting in a thicker interfacial layer around oil droplets. This fortified interfacial layer, in synergy with steric hindrance, bolstered resistance to pH changes, salt ions, and thermal degradation. Moreover, HIPEs stabilized with glycated YCP exhibited reduced oxidation rates and improved CUR protection. In vitro digestion studies demonstrated enhanced CUR bioaccessibility, attributed to a faster release of fatty acids. This study underscores the efficacy of glycation as a strategic approach to augment the applicability of biomass proteins, exemplified by glycated YCP, in formulating stable and functional HIPEs for diverse food applications.

Nanocarrier-mediated curcumin delivery: An adjuvant strategy for CNS disease treatment.

Neurological disorders are a major global challenge, which counts for a substantial slice of disease burden around the globe. In these, the challenging landscape of central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and neuro-AIDS, demands innovative and novel therapeutic approaches. Curcumin, a versatile natural compound with antioxidant and anti-inflammatory properties, shows great potential as a CNS adjuvant therapy. However, its limited bioavailability and suboptimal permeability to the blood-brain barrier (BBB) hamper the therapeutic efficacy of curcumin. This review explores how nanocarrier facilitates curcumin delivery, which has shown therapeutic efficacy for various non-CNS diseases, for example, cancers, and can also revolutionize the treatment outcomes in patients with CNS diseases. Toward this, intranasal administration of curcumin as a non-invasive CNS drug delivery route can also aid its therapeutic outcomes as an adjuvant therapy for CNS diseases. Intranasal delivery of nanocarriers with curcumin improves the bioavailability of curcumin and its BBB permeability, which is instrumental in promoting its therapeutic potential. Furthermore, curcumin's inhibitory effect on efflux transporters will help to enhance the BBB and cellular permeability of various CNS drugs. The therapeutic potential of curcumin as an adjuvant has the potential to yield synergistic effects with CNS drugs and will help to reduce CNS drug doses and improve their safety profile. Taken together, this approach holds a promise for reshaping CNS disease management by maximizing curcumin's and other drugs' therapeutic benefits.

Topical Delivery of Methoxsalen Co-loaded Curcumin Using Hybrid Nanocarrier-Based Polymeric Hydrogel for Synergistic Therapy in the Treatment of Psoriasis

Topical Delivery of Methoxsalen Co-loaded Curcumin Using Hybrid Nanocarrier-Based Polymeric Hydrogel for Synergistic Therapy in the Treatment of Psoriasis

Ultrasound-assisted alkaline hydrolysis of fish(Cyprinus carpio L.) scale gelatin: A possible curcumin delivery system with increased water solubility and sustained release

This study investigated the effect of ultrasound-assisted alkaline treatment on the structural characteristics and curcumin loading efficiency in fish scale gelatin (FSG). The results showed that FSG treated with a combination of ultrasound and alkaline hydrolysis outperformed non-treated FSG, as well as alkaline- or ultrasound-treated FSG in augmenting curcumin loading efficiency (from 3.02 to 18.36 μg/mL). In contrast to FSG exposed to single treatments (alkaline or ultrasound), the FSG subjected to combined treatment exhibited a notably higher ratio of hydrophobic amino acids (47.51 ± 2.27%) and protein elution amount (180.87 μg/mL). Meanwhile, single and combined treatments significantly modified the molecular conformation as well as the microstructure of FSG, transforming the α-helical conformation to the β-sheet structure and presenting an ordered structure with increased voids. The curcumin-loaded FSG subjected to ultrasound-assisted alkaline treatment revealed a sustained release profile under simulated gastrointestinal conditions. The elucidated outcomes underscore the significant potential of FSG subjected to ultrasound-assisted alkaline treatment as a promising avenue for facilitating the controlled delivery of bioactive hydrophobic nutrients.