Bioactive Delivery Research Articles

Harnessing exosomes and plant-derived exosomes as nanocarriers for the efficient delivery of plant bioactives.

Exosomes, a category of extracellular vesicle (EV), are phospholipid bilayer structures ranging from 30 to 150nm, produced by various organisms through the endosomal pathway. Recent studies have established the utilization of exosomes as nanocarriers for drug distribution across various therapeutic areas including cancer, acute liver injury, neuroprotection, oxidative stress, inflammation, etc. The importance of plant-derived exosomes and exosome vesicles derived from mammalian cells or milk, loaded with potent plant bioactives for various therapeutic indications are discussed along with insights into future perspectives. Moreover, this review provides a detailed understanding of exosome biogenesis, their composition, classification, stability of different types of exosomes, and different routes of administration along with the standard techniques used for isolating, purifying, and characterizing exosomes.

Hybrid crystalline bioparticles with nanochannels encapsulating acemannan from Aloe vera: Structure and interaction with lipid membranes

Smart nanocarrier-based bioactive delivery systems are a current focus in nanomedicine for allowing and boosting diverse disease treatments. In this context, the design of hybrid lipid-polymer particles can provide structure-sensitive features for tailored, triggered, and stimuli-responsive devices. In this work, we introduce hybrid cubosomes that have been surface-modified with a complex of chitosan-N-arginine and alginate, making them pH-responsive. We achieved high-efficiency encapsulation of acemannan, a bioactive polysaccharide from Aloe vera, within the nanochannels of the bioparticle crystalline structure and demonstrated its controlled release under pH conditions mimicking the gastric and intestinal environments. Furthermore, an acemannan-induced phase transition from Im3m cubic symmetry to inverse hexagonal HII phase enhances the bioactive delivery by compressing the lattice spacing of the cubosome water nanochannels, facilitating the expulsion of the encapsulated solution. We also explored the bioparticle interaction with membranes of varying curvatures, revealing thermodynamically driven affinity towards high-curvature lipid membranes and inducing morphological transformations in giant unilamellar vesicles. These findings underscore the potential of these structure-responsive, membrane-active smart bioparticles for applications such as pH-triggered drug delivery platforms for the gastrointestinal tract, and as modulators and promoters of cellular internalization.

Half-Curcuminoids Encapsulated in Alginate-Glucosamine Hydrogel Matrices as Bioactive Delivery Systems.

The therapeutic effects of curcumin and its derivatives, based on research in recent years, are limited by their low bioavailability. To improve bioavailability and develop the medical field of application, different delivery systems have been developed that are adapted to certain environments or the proposed target type. This study presents some half-curcuminoids prepared by the condensation of acetylacetone with 4-hydroxybenzaldehyde (C1), 4-hydroxy-3-methoxybenzaldehyde (C2), 4-acetamidobenzaldehyde (C3), or 4-diethylaminobenzaldehyde (C4), at microwaves as a simple, solvent-free, and eco-friendly method. The four compounds obtained were characterized in terms of morphostructural and photophysical properties. Following the predictions of theoretical studies on the biological activities related to the molecular structure, in vitro tests were performed for compounds C1-C3 to evaluate the antitumor properties and for C4's possible applications in the treatment of neurological diseases. The four compounds were encapsulated in two types of hydrogel matrices. First, the alginate-glucosamine network was generated and then the curcumin analogs were loaded (G1, G3, G5-G7, and G9). The second type of hydrogels was obtained by loading the active compound together with the generation of the hydrogel carrier matrices, by simply dissolving (G4 and G10) or by chemically binding half-curcuminoid derivatives to glucosamine (G2 and G8). Thus, two types of curcumin analog delivery systems were obtained, which could be applied in various types of medical treatments.

Emerging Trends in Bioavailability and Pharma-Nutraceutical Potential of Whey Bioactives.

Whey, a component of milk and a useful by-product of the dairy industry's casein and cheese-making, has been used for generations to augment animal feed. It contains a range of proteins, including α-lactalbumin, β-lactoglobulin, bovine serum albumin, heavy and light chain immunoglobulins, lactoferrin, glycomacropeptide, and lactoperoxidase. Whey proteins exhibit great potential as biopolymers for creating bioactive delivery systems owing to their distinct health-enhancing characteristics and the presence of numerous amino acid groups within their structures. Whey has considerable factors such as antitumor, anti-inflammatory, antihypertensive, hypolipidemic, antiviral, and antibacterial properties in addition to chelating. The global market of whey protein stood at USD 5.33 billion in 2021, with a projected compound annual growth rate of 10.48% spanning the interval from 2022 to 2030. The escalating demand for whey protein is intrinsically linked to the amplifying consciousness surrounding healthy lifestyles. Notably, protein supplements are recurrently endorsed by fitness and sports establishments, thereby accentuating the focal point of customers toward whey protein. This review focuses on nutritional composition, whey bioactives, and their bioavailability with potential health benefits.

Nanostructured lipid carrier loaded with Zingiber officinale oil to enhance transdermal bioactive delivery for topical formulation

This study reported on the enhancement of Zingiber officinale (Z. officinale) oil delivery, a bioactive with poor water solubility, by incorporating it into nanostructured lipid carriers (NLC) for transdermal bioactive delivery in topical formulations using the ultrasonication technique with a D–optimal mixture design approach. The independent factors in the process included the percentage of Z. officinale oil, solid lipid (glyceryl monostearate (GMS)), and liquid lipid (virgin coconut oil (VCO)). The study characterized the NLC– Z. officinale oil formulation based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) as the dependent variables. Besides, Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR–ATR), and Differential Scanning Calorimetry (DSC) were also employed. The optimized NLC–Z. officinale oil formulation, comprising 0.36 % Z. officinale oil, 0.14 % solid lipid (GMS), and 0.50 % liquid lipid (VCO). The study's results demonstrated that the finely tuned NLC– Z. officinale oil formulation, with an average diameter of 90.71 ± 9.48 nm, a PDI of 0.147 ± 0.01, a ZP of –45.7 ± 0.67 mV, and an EE of 88.80 ± 11.18 %, exhibited a controlled and sustained release profile following the Korsmeyer–Peppas model. The in vitro penetration studies on excised Sprague–Dawley rat skin and Strat–M® showcased the heightened penetration flux of NLC–Z. officinale oil compared to Z. officinale oil. Furthermore, in vivo distribution studies in female Sprague–Dawley rats underscored the deep penetration of NLCs into the dermal layer after 12 h of application. Notably, a 3–hour treatment with NLC–Z. officinale oil triggered the release of free fatty acids (FFA). The 90 days storage stability study revealed no significant changes in NLC– Z. officinale oil concerning PS and PDI, affirming its stability over time. These findings illuminated the potential applications of NLC– Z. officinale oil as a robust transdermal bioactive delivery system for Z. officinale oil. This underscored its significance in pharmaceutical formulations, providing a novel avenue for therapeutic purposes.

Encapsulation of Lavandula austroapennina N.G. Passal., Tundis & Upson extracts: Focus on leaf and stem enriched liposome for cosmeceutical innovation

In the framework aimed at valorizing Lavandula austroapennina N.G. Passal., Tundis & Upson, an endemic species of the Apennine mountains of southern Italy, through the deep investigation of its organ chemical composition and bioactivity, innovative cosmeceutical applications are of interest. Thus, lipophilic and alcoholic extracts, at dose levels avoiding cytotoxicity in keratinocytes, were encapsulated into liposomes by applying thin-film hydration method. This was aimed to overcome known plant extract issues, such as poor solubility, high instability, and low skin permeation. The lipid-based vesicles were characterized by particle size dimension ≤300 nm, negative charge (-8 to −20 mV) and polydispersity index <0.3. Entrapment efficiency distinguished liposomes encapsulating alcoholic extracts from corolla- and calyx for their highest flavonoids, while those with leaf- and root alcoholic extracts excelled in phenolic acids and their conjugates. Among lipophilic extracts, those from corolla, calyx and stem provided liposomes entrapping the highest lipid content. These data, together with the greater bioactivity of alcoholic leaf, and lipophilic stem extract, allowed us to further investigate these two extracts for their cosmeceutical applicability. Accordingly, extracts-containing liposomes, preliminarily characterized by ATR-FTIR spectroscopy, underwent cytotoxic and healing capability assessment towards HaCaT cells. The extracts-enriched liposomes showed a healing capacity higher than the parental extracts from which they derived. Evaluating the percutaneous absorption by Franz Cells assay, followed by UHPLC-QqTOF-HR-MS-based quali-quantitative analysis, revealed that encapsulation in liposomes improved bioactive delivery through/into a specific skin layer. These results, while suggesting the effectiveness of liposome-based nanoparticles in improving the bioavailability and biological activity of specialized metabolites, reinforce the cosmeceutical use of L. austroapennina extracts.

Nano-Food Farming: Toward Sustainable Applications of Proteins, Mushrooms, Nano-Nutrients, and Nanofibers

The relationship between agriculture and food is very close. It is impossible to produce adequate crops for global food security without proper farm management. Farming practices represent direct and indirect controlling factors in terms of global food security. Farming management practices influence agro-food production from seed germination through to the post-harvest treatments. Nano-farming utilizes nanotechnologies for agricultural food production. This review covers four key components of nano-farming: nano-mushroom production, protein-based nanoparticles, nano-nutrients, and nanofibers. This provides a comprehensive overview of the potential applications of nanotechnology in agriculture. The role of these components will be discussed in relation to the challenges faced and solutions required to achieve sustainable agricultural production. Edible mushrooms are important to food security because they are a nutritious food source and can produce nanoparticles that can be used in the production of other food sources. Protein-based nanoparticles have considerable potential in the delivery of bioactives as carriers and other applications. Nano-nutrients (mainly nano-selenium, nano-tellurium and carbon nanodots) have crucial impacts on the nutrient status of plant-based foods. Carbon nanodots and other carbon-based nanomaterials have the potential to influence agricultural crops positively. There are promising applications of nanofibers in food packaging, safety and processing. However, further research is needed to understand the impacts and potential risks of nanomaterials in the food production system.

Controllable Dopamine Conjugation Boosts Fluorescence, Biocompatibility, and PET Imaging‐Guided Toxicity Assessment of Polycations

AbstractAs well known in bioactives delivery and cancer/inflammation theranostics, polycations have recently extended their biomedical potentials in reducing visceral fat, embolizing body fluid, modulating blood coagulation, and ameliorating hyperammonemia. However, positive charges that dominate various action mechanisms, often raise risks in biosafety concerns. Also, the lack of intrinsic imaging properties of polycations makes it challenging to uncover their pharmacokinetic profiles in living objects. Herein, dopamine conjugation is demonstrated controllable and highly efficient in boosting the fluorescence or even white color emission of various polycations including hyperbranched poly(amido amine) (HPAA), polyethyleneimine and poly‐L‐lysine. By shielding partial surface positive charges, increasing hydrophobicity, and inducing aqueous self‐assembly, dopamine conjugation can significantly enhance the biocompatibility and decrease the toxicity and immunogenicity of polycations. Furthermore, the catechol‐metal binding interaction facilitates the accessibility of polycation‐based positron emission tomography (PET) probes. Different tissue uptake and biodistributions of gallium‐68‐radiolabeled HPAA before and after dopamine conjugation indicate that PET imaging can be a useful supplement to evaluate the dynamic toxicities of polycations.

Development and performance evaluation of self-assembled pH-responsive curcumin-bacterial exopolysaccharide micellar conjugates as bioactive delivery system

The present study reports the synthesis of micellar conjugates, wherein curcumin (Cur), a bioactive compound with poor bioavailability, was covalently bonded to a bacterial exopolysaccharide (EPS). These conjugates were synthesized by utilizing succinic acid that linked Cur to the pyranosyl moiety of the EPS. The Cur-EPS conjugates appeared as spherical micelles in aqueous solution and were found to have an average hydrodynamic diameter of 254 ± 2.7 nm. The micellar conjugates showed superior stability than Cur as evident from their negative surface charge (−27 ± 1.8 mV) and low polydispersity index (PDI) (0.33 ± 0.04). The in vitro studies on release kinetics helped elucidate the pH-responsive characteristics of the Cur-EPS conjugate, as 87.50 ± 1.45 % of Cur was released at an acidic pH of 5.6, in contrast to 30.15 ± 2.61 % at systemic pH of 7.4 at 150 h. The conjugates were hemocompatible and exhibited cytotoxic effect against the osteosarcoma cell line (MG-63) after 48 h treatment. They also demonstrated superior antibacterial, antibiofilm, and antioxidant activities in comparison to free Cur. Therefore, the Cur-EPS conjugates have potential pharmaceutical applications as therapeutic biomaterial that can be applied as a drug delivery system.

Flavonoid-Labeled Biopolymer in the Structure of Lipid Membranes to Improve the Applicability of Antioxidant Nanovesicles.

Nanovesicles produced with lipids and polymers are promising devices for drug and bioactive delivery and are of great interest in pharmaceutical applications. These nanovesicles can be engineered for improvement in bioavailability, patient compliance or to provide modified release or enhanced delivery. However, their applicability strongly depends on the safety and low immunogenicity of the components. Despite this, the use of unsaturated lipids in nanovesicles, which degrade following oxidation processes during storage and especially during the proper routes of administration in the human body, may yield toxic degradation products. In this study, we used a biopolymer (chitosan) labeled with flavonoid (catechin) as a component over a lipid bilayer for micro- and nanovesicles and characterized the structure of these vesicles in oxidation media. The purpose of this was to evaluate the in situ effect of the antioxidant in three different vesicular systems of medium, low and high membrane curvature. Liposomes and giant vesicles were produced with the phospholipids DOPC and POPC, and crystalline cubic phase with monoolein/DOPC. Concentrations of chitosan-catechin (CHCa) were included in all the vesicles and they were challenged in oxidant media. The cytotoxicity analysis using the MTT assay (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) revealed that concentrations of CHCa below 6.67 µM are non-toxic to HeLa cells. The size and zeta potential of the liposomes evidenced the degradation of their structures, which was minimized by CHCa. Similarly, the membrane of the giant vesicle, which rapidly deteriorated in oxidative solution, was protected in the presence of CHCa. The production of a lipid/CHCa composite cubic phase revealed a specific cubic topology in small-angle X-ray scattering, which was preserved in strong oxidative media. This study demonstrates the specific physicochemical characteristics introduced in the vesicular systems related to the antioxidant CHCa biopolymer, representing a platform for the improvement of composite nanovesicle applicability.

Lipid-based nanocarriers for enhanced delivery of plant-derived bioactive molecules: a comprehensive review.

Bioactive compounds derived from plants have been investigated for treating various pathological conditions. However, the utilization of these compounds has challenges such as instability, low solubility and bioavailability. To overcome these challenges, the encapsulation of bioactive molecules with in a novel nano carrier system enabling effective delivery and clinical translation has become essential. Lipid-based nanocarriers provide versatile platforms for encapsulating and delivering bioactive compounds and overcome the challenges. These novel carriers can improve solubility, stability, improved drug retention and therapeutic efficacy of plant derived bioactive compounds. The current review evaluates the challenges in delivery of plant bioactives and highlights the potential of various lipid-based nano carriers designed to improve its therapeutic efficacy.

Strategies for utilizing covalent organic frameworks as host materials for the integration and delivery of bioactives.

Covalent organic frameworks (COFs), a new and developing class of porous framework materials, are considered a type of promising carrier for the integration and delivery of bioactives, which have diverse fascinating merits, such as a large specific surface area, designable and specific porosity, stable and orderly framework structure, and various active sites. However, owing to the significant differences among bioactives (including drugs, proteins, nucleic acid, and exosomes), such as size, structure, and physicochemical properties, the interaction between COFs and bioactives also varies. In this review, we firstly summarize three strategies for the construction of single or hybrid COF-based matrices for the delivery of cargos, including encapsulation, covalent binding, and coordination bonding. Besides, their smart response release behaviors are also categorized. Subsequently, the applications of cargo@COF biocomposites in biomedicine are comprehensively summarized, including tumor therapy, central nervous system (CNS) modulation, biomarker analysis, bioimaging, and anti-bacterial therapy. Finally, the challenges and opportunities in this field are briefly discussed.

Micellar delivery systems of bioactive compounds for precision nutrition.

Rapid changes in lifestyle and the increasingly hectic pace of life have led to a rise in chronic diseases, such as obesity, inflammatory bowel disease, liver disease, and cancer, posing significant threats to public health. In response to these challenges, precision nutrition (PN) has emerged as a secure and effective intervention aiming at human health and well-being. Bioactive compounds (bioactives), including carotenoids, polyphenols, vitamins, and polyunsaturated fatty acids, exhibit a range of beneficial properties, e.g., antioxidant and anti-inflammatory effects. These properties make them promising candidates for preventing or treating chronic diseases and promoting human health. However, bioactives might have different challenges when incorporated into food matrices and oral administration, including low water solubility, poor physiochemical stability, and low absorption efficiency. This limits them to achieve the health benefits in the body. Numerous strategies have been developed and utilized to encapsulate and deliver bioactives. Micellar delivery systems, due to their unique core-shell structure, play a pivotal role in improving the stability, solubility, and bioavailability of these bioactives. Moreover, through innovative design strategies, micellar delivery systems can be tailored to offer targeted and controlled release, thus maximizing the potential of bioactives in PN applications. This chapter reveals details about the preparation methods and properties of micelles and highlights the strategies to modulate the properties of polymeric micelles. Afterwards, the application of polymeric micelles in the delivery of bioactives and the corresponding PN, including controlled release, organ-targeting ability, and nutritional intervention for chronic disease are summarized.

Formulation of vegan nutritional gummy supplements and their textural-organoleptic analysis

Gummy supplements are an exceptional medium for delivering pharmaceuticals and nutritional bioactives, especially for children. Interestingly, they are increasingly finding favor among adults as effective bioactive delivery systems. This study aimed to identify and select natural vegan components for creating and developing gummy prototypes. The gelling agent was agar-agar, sourced from red algae, and combined with carrageenan to enhance compressibility. Phycocyanin from Spirulina and anthocyanin from purple cabbage were used as colorants to provide a range of natural hues. The study resulted in five distinct formulations: Blueberry Anthocyanin Vitamin D (BAD), Blueberry Anthocyanin Vitamin C (BAC), Mango Antacid Anthocyanin (MAA), Mango Flavored Phycocyanin (MFP), and Kiwi Flavored Spirulina (KFS) gummies. Notably, the MAA gummy exhibited suboptimal texture quality during preliminary assessments and was consequently excluded from further analysis.Across the formulations, no visible color changes were noted upon room temperature storage for a week. The BAD gummy displayed heightened adhesiveness and springiness in texture, while the KFS gummy demonstrated superior cohesiveness, chewiness, and gumminess in its fresh state.Interestingly, the BAD gummy exhibited the highest adhesion even in the one-week-old samples.The outcome of the 9-point hedonic sensory evaluation unveiled that the cyan shade, derived from the phycocyanin pigment of Spirulina, was the most preferred color among the gummies. Regarding overall likability, the MFP and BAC formulations garnered the highest responses for being 'liked extremely'. The uniqueness of the present work lies in its meticulous exploration and selection of natural vegan ingredients to craft gummy formulations with diverse bioactive and sensory attributes.

Hydrophilic or hydrophobic coating of whey protein aerogels obtained by supercritical-CO2-drying: Effect on physical properties, moisture adsorption and interaction with water and oil in food systems

Aerogel monoliths, prepared by water-to-ethanol substitution and supercritical-CO2-drying of whey protein hydrogels, were dip-coated with hydrophilic (alginate, AL; agar, AG) or hydrophobic (ethylcellulose, EC) polymers. AL coating induced aerogel collapse, due to solvent absorption. AG and EC rapidly set onto aerogel surface, forming layers of 65 and 100 μm thickness, respectively. While AG-coating induced 20% volume shrinkage, 25% apparent density increase and 75% firmness increase, EC-coating maintained the original aerogel structure. Upon exposure to 100% equilibrium relative humidity, aerogels showed moisture uptake in the order AG-coated>uncoated>EC-coated. When immersed in water or oil, the AG-coated aerogel showed an uptake respectively 40 and 60% lower than the uncoated control. The oil barrier capacity of AG-coated aerogel was also demonstrated in a lipid food system (stearin-oil mixture). Although not reducing oil uptake, EC-coating reduced water uptake by 30% and its water barrier properties were demonstrated upon immersion in an aqueous food system (water-flour batter). Industrial relevanceThe obtained results indicate tailored coating as a feasible strategy to enhance aerogel functionality in food. This would open further possibilities, including the use of aerogels as smart food ingredients able to modulate aroma and bioactive delivery both in the food product and during digestion. These findings are thus important in supporting the industrial development of aerogel-based ingredients with customized functionalities.

New approaches for modulation of alginate-chitosan delivery properties

Alginate is a biopolymer widely used on delivery systems when bioactive protection at acidic pH is required, while chitosan can enhance mucoadhesion and controlled release at alkaline pHs. In this work, alginate ionotropic gelation and electrostatic complexation to chitosan were evaluated concomitantly or in a two-step approach to improve the delivery properties of systems in different pHs. The effect of pH on alginate gelation and chitosan interactions were also evaluated. Alginate microspheres were prepared by ionotropic gelation in CaCl2 at different pH values (2.5 and 6.0) by extrusion. Complexation with chitosan was carried out during alginate ionotropic gelation (one-step approach) or after alginate gel formation (two-step approach). Alginate microparticles without chitosan showed larger pores and lower mechanical strength. Extruded microspheres at pH 6.0 were more stable to pH and showed smaller pores than the formed at pH 2.5. One-step production retained a large amount of bioactive at pH 7.0 and resulted in lower release at the pH of intestinal digestion. The two-step approach retained less amount of bioactive but confer more protection to the pH of the stomach phase and higher release in pH of the intestinal phase than one-step samples. These results indicate that the formation of alginate gels by ionotropic gelation followed by the complexation with chitosan (in two-step) is promising for the transport and delivery of bioactives into intestinal conditions, whereas the ionotropic gelation concomitantly to electrostatic complexation (one-step approach) is indicated to the delivery of bioactives into lower pH environments.

Biomimetic hybrid nanovesicles improve infected diabetic wound via enhanced targeted delivery

Infected diabetic wounds have been raising the global medical burden because of its high occurrence and resulting risk of amputation. Impaired endothelium has been well-documented as one of the most critical reasons for unhealed wounds. Recently, endothelial cell-derived nanovesicles (NVs) were reported to facilitate angiogenesis, whereas their efficacy is limited in infected diabetic wounds because of the complex niche. In this study, extrusion-derived endothelial NVs were manufactured and then hybridized with rhamnolipid liposomes to obtain biomimetic hybrid nanovesicles (HNVs). The HNVs were biocompatible and achieved endothelium-targeted delivery through membrane CXCR4-mediated homologous homing. More importantly, the HNVs exhibited better penetration and antibacterial activity compared with NVs, which further promote the intrinsic endothelium targeting in infected diabetic wounds. Therefore, the present research has established a novel bioactive delivery system—HNV with enhanced targeting, penetration, and antibacterial activity—which might be an encouraging strategy for infected diabetic wound treatment.

Digestive characteristics of astaxanthin oil in water emulsion stabilized by a casein-caffeic acid–glucose ternary conjugate

To overcome the barrier of poor oral bioavailability of astaxanthin, a stable oil-in-water emulsion was constructed using casein-caffeic acid–glucose ternary conjugates (CSC) to deliver astaxanthin, and its gastrointestinal behavior was evaluated in vitro with sodium caseinate (CSN) as a control. Results showed that, CSC-stabilized emulsion shower better resistance to the adverse conditions of the gastric environment than CSN-stabilized emulsion, and exhibited lower average particle size and aggregation (4972.33 nm, −5.93 mv) after simulated gastric digestion. Besides, after simulated intestinal digestion, the reducing capacity and astaxanthin transfer efficiency of CSC emulsion into the micellar phase were 686.74 μmol Trolox/100 mL and 26.2 %, which were 2.6 and 4.05-fold higher than that of CSN emulsion. The above results suggest that CSC can be used for better delivery of astaxanthin, which could be useful in designing foods such as functional beverages, pharmaceuticals and nutritional supplements for delivery of lipophilic bioactives.

Formation of soy protein nanoparticles with varied loading capacity by controlled enzymatic hydrolysis and their co-assembly with Vitamin D3

In the present study, rational designed soy protein nanoparticles (SNPs) with different subunit compositions and loading capacities were fabricated via Pancreatin-induced hydrolysis taken Vitamin D3 (VD3) as a hydrophobic cargo. Further assembly behavior of SNPs caused by VD3 incorporation was also noticed and analyzed. Results showed that hydrolysis to 2.98% degree of hydrolysis (DH) (Pan1) facilitated the formation of a nanoparticle structure with hydrophobic cores originated from moderate degradation of 7 S and A subunits of 11 S. This core-shell structure had a higher loading capacity towards the VD3 and was further strengthened upon VD3 addition. Further hydrolysis to 10.96% DH (Pan2) caused further degradation of subunits and the extension of protein structure, accelerating aggregation through protein-protein interactions. The coexistence of aggregates as well as degradation fragments showed different binding patterns with VD3 and the resultant mixture was in non-uniformed size distribution. Further hydrolysis to 18.04% DH (Pan3) caused severe precipitation due to hydrophobic aggregation and the hydrophilic peptides retained had no apparent hydrophobic domain for the entrapment of VD3. Interestingly, VD3 would tend to form a hydrophobic core in situ through hydrophobic hydration with Pan3, resulting in a more ordered structure. These findings suggest that enzymatic hydrolysis could be a useful tool for the rational design of nanostructure for bioactive delivery where the co-assembly behavior calls for attention.

Construction of self-assembled nano cellulose crystals/chitosan nanobubbles composite hydrogel with improved gallic acid release property

Hydrogels are of great significance in the field of bioactive delivery. This study designed the self-assembly of gallic acid-loaded nano cellulose crystals/chitosan (NC/CS) hydrogels via Nano bubbles (NBs). NC/CS NBs 4:2 hydrogels improved the mechanical properties compared to those without NBs. The hardness of NC/CS (4:2) NBs hydrogels was greatly enhanced by 1.15 ± 0.05. The water-holding and swelling behavior can be tuned at different ratios. NC/CS NBs (4:2) showed the electrostatic interaction analyzed by FTIR, XRD, and XPS. SEM results displayed smoother and smaller pores along dense networks promoted by NBs. The antioxidant activity of hydrogels was increased by adding NBs (P < 0.05). In vitro and vivo release activity of gallic acid was higher in simulated intestinal fluid (SIF) at 4:2, depicting the controlled release mechanism. Thus, current work revealed that NBs and low concentrations of NC can be self-assembled with chitosan chains, producing a highly compact hydrogel structure.