pH-responsive chitosan-mediated spherical mesoporous silica microspheres for high loading and controlled delivery of 5-Fluorouracil.

The objective of this study is to develop a drug carrier to overcome the inherent drawbacks of 5-Fluorouracil (5-Fu), including low bioavailability, short half-life, and systemic toxicity. In the present work, mesoporous silica nanoparticles (MSNs) capped by chitosan (CS) to encapsulate 5-Fu (5-Fu MSNs/CS) were fabricated by the sol-gel process, ultrasonic impregnation, and emulsion cross-linking. The 5-Fu MSNs/CS microspheres exhibit pH-responsive drug release and remarkable drug encapsulation capacity, as well as perfect sphericity, high specific surface area (680.62 cm2/g), and uniform particle size (2.64 ± 0.05 µm). The drug-loading content and encapsulation efficiency are 14.12 ± 0.53 % and 82.21 ± 2.13 %, respectively. The cumulative release of 5-Fu from MSNs/CS microspheres is fast and sustained at pH 5.0 (89.56 ± 0.97 %) compared to that at pH 7.4 (57.88 ± 0.91 %) in 96 h, and it is Fickian diffusion controlled. In conclusion, the MSNs/CS microspheres prepared in this study could be potential carriers for 5-Fu delivery.

Film Coating of Phosphorylated Mandua Starch on Matrix Tablets for pH-Sensitive Release of Mesalamine.

Chemically modified mandua starch was successfully synthesized and applied to coat mesalamine-loaded matrix tablets. The coating material was an aqueous dispersion of mandua starch modified by sodium trimetaphosphate and sodium tripolyphosphate. To investigate the colon-targeting release competence, chemically modified mandua starch film-coated mesalamine tablets were produced using the wet granulation method followed by dip coating. The effect of the coating on the colon-targeted release of the resultant delivery system was inspected in healthy human volunteers and rabbits using roentgenography. The results show that drug release was controlled when the coating level was 10% w/w. The release percentage in the upper gastric phase (pH 1.2, simulated gastric fluid) was less than 6% and reached up to 59.51% w/w after 14 h in simulated colonic fluid. In addition to in vivo roentgenographic studies in healthy rabbits, human volunteer studies proved the colon targeting efficiency of the formulation. These results clearly demonstrated that chemically modified mandua starch has high effectiveness as a novel aqueous coating material for controlled release or colon targeting.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

pH-sensitive semi-interpenetrating network of microcrystalline cellulose and methacrylic acid hydrogel for the oral delivery of insulin.

Insulin is commonly administered to diabetic patients subcutaneously and has shown poor patient compliance. Due to this, research has been carried out extensively to find molecules that could deliver insulin orally. In this context, a new type of pH-responsive hydrogel, composed of microcrystalline cellulose and methacrylic acid-based hydrogels, has been developed and studied for the oral delivery of insulin. These hydrogels were prepared by free radical polymerization using potassium persulphate as initiator and N, N'-methylenebisacrylamide as a cross-linker. These pH-sensitive hydrogels showed swelling in distilled water as high as 5800 %. The hydrogels were investigated for swelling in saline and glucose solutions, and pH sensitivity was confirmed by swelling in solutions of different pH. The morphological shape was established by SEM, and the structure was analyzed by FTIR. Thermal degradation was investigated by TGA. In vitro release studies have confirmed pH sensitivity, showing lower insulin release at pH 1.2 than at pH 6.8. The encapsulation efficiency was determined to be 56.00 ±â€¯0.04 %. It was further validated by in-vivo investigations for which insulin was loaded into hydrogels and administered orally to healthy and diabetic Wistar rats at 40 IU/kg, showing maximum hypoglycemic effect at 6 h, which was sustained for 24 h. In the stomach's acidic environment, the gels remained unaffected due to the formation of intermolecular polymer complexes. Insulin remained in the gel and was protected from proteolytic degradation. Thus, pH-responsive methacrylic acid-based hydrogels are promising for biomedical applications, especially oral drug delivery.

A review on the role of pH-sensitive natural pigments in biopolymers based intelligent food packaging films.

As food packaging evolves, consumer interests are shifting from traditional to intelligent food packaging systems. Intelligent packaging includes active components that display changes in a visual or interactive form perceivable by consumers. This offers real-time monitoring of the quality and shelf life of the packaged food and enhances transparency. For example, pH-sensitive natural pigment-based films change color in response to variations in pH levels, enabling the film/labels to reflect alterations in the acidity or basicity of the food inside the package. Natural pigments like anthocyanins, curcumin, betalains, chlorophyll, and carotenoids have been comprehensively reported for developing biodegradable pH-sensitive films of starch, protein, chitosan, and cellulose. Natural pigments offer great compatibility with these biopolymers and improve the other performance parameters of the films. However, these films still lack the strength and versatility of petroleum-based synthetic plastic films. But these films can be used as an indicator and combined with primary packaging to monitor freshness, time-temperature, and leak for muscle foods, dairy products, fruits and vegetables, and bakery products. Therefore, this review provides a detailed overview of pH-sensitive pigments, their compatibility with natural polymers, their role in film performance in monitoring, and their food packaging applications.

A versatile bilayer smart packaging based on konjac glucomannan/alginate for maintaining and monitoring seafood freshness.

This study introduces a novel multi-functional double-layer intelligent packaging. It focuses on developing a dual-function system capable of real-time monitoring and freshness preservation. Specifically, cellulose nanocrystalline (CNC) was obtained through acid hydrolysis, and then CNC/soybean protein isolate (CNC/SPI) complex colloid particles were prepared via antisolvent method. These particles served as stabilizers to prepare oil-in-water (O/W) cinnamon essential oil Pickering emulsion (CSCEO). The CSCEO was then integrated into the emulsified hydrophobic layer of a konjac glucomannan (Kgm) matrix through intermolecular hydrogen bonding. Finally, alginate (Alg) matrix containing alizarin (Al) as an indicator was added to construct the bilayer structure using a layer-by-layer casting strategy. The inner layer Alg/Al was the pH/NH3-responsive indicator layer, while the outer layer Kgm/CSCEO acted as the high-barrier bacteriostatic layer. The obtained dual-function, double-layer film (Alg/Al-Kgm/CSCEO), which possesses a sensitive, reversible and rapid response towards pH/NH3, shows exceptional antibacterial and antioxidant properties, as well as excellent mechanical property, light-blocking capability and hydrophobicity. For monitoring and maintaining the actual freshness of shrimp, such a bilayer packaging displays smallest change of ∆E and TVB-N (18.65 mg/100 g) even after 72 h, which further highlighting its potential in enhancing food safety and extending shelf life.

Reconstruction of TNF-α with specific isoelectric point released from SPIONs basing on variable charge to enhance pH-sensitive controlled-release.

The clinical application of tumor necrosis factor-α (TNF-α) is limited by its short half-life, subeffective concentration in the targeted area and severe systemic toxicity. In this study, the recombinant polypeptide S4-TNF-α was constructed and coupled with chitosan-modified superparamagnetic iron oxide nanoparticles (S4-TNF-α-SPIONs) to achieve pH-sensitive controlled release and active tumor targeting activity. The isoelectric point (pI) of S4-TNF-α was reconstructed to approach the pH of the tumor microenvironment. The negative-charge S4-TNF-α was adsorbed to chitosan-modified superparamagnetic iron oxide nanoparticles (CS-SPIONs) with a positive charge through electrostatic adsorption at physiological pH. The acidic tumor microenvironment endowed S4-TNF-α with a zero charge, which accelerated S4-TNF-α release from CS-SPIONs. Our studies showed that S4-TNF-α-SPIONs displayed an ideal pH-sensitive controlled release capacity and improved antitumor effects. Our study presents a novel approach to enhance the pH-sensitive controlled-release of genetically engineered drugs by adjusting their pI to match the pH of the tumor microenvironment.

The smart nanocarrier containing zein/starch co-biopolymers enhanced by graphitic carbon nitride; exploring opportunities in brain cancer treatment.

In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-C3N4) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix's entrapment and loading efficiency are greatly improved by adding g-C3N4 nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of -42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-C3N4@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-C3N4@5-FU as a productive and targeted therapeutic approach for cancer cells.

Targeted chemo-phototherapy in red light with novel doxorubicin and iron(III) complex-functionalized gold nanoconjugate (Dox-Fe@FA-AuNPs).

The anticancer efficacy of doxorubicin, an anthracycline-based and FDA-approved chemotherapeutic drug, is significantly hindered by acquired chemoresistance and severe side effects, despite its potent anticancer properties. To overcome these challenges, we developed an innovative therapeutic formulation that integrates targeted chemotherapy and phototherapy within a single platform using gold nanoparticles (AuNPs). This novel nanoconjugate, designated as Dox-Fe@FA-AuNPs, is co-functionalized with folic acid, doxorubicin, and an iron(III)-phenolate/carboxylate complex, enabling cancer-specific drug activation. Here, we report the synthesis, characterization, and comprehensive physico-chemical and biological evaluations of Dox-Fe@FA-AuNPs. The nanoconjugate exhibited excellent solubility, stability, and enhanced cellular uptake in folate receptor-positive cancer cells. The nanoconjugate was potently cytotoxic against HeLa and MDA-MB-231 cancer cells (HeLa: 105.5 ± 16.52 µg mL-1; MDA-MB-231: 112.0 ± 12.31 µg mL-1; MDA-MB-231 (3D): 156.31 ± 19.35 µg mL-1) while less cytotoxic to the folate(-) cancer cells (MCF-7, A549 and HepG2). The cytotoxicity was attributed to the pH-dependent release of doxorubicin, which preferentially occurs in the acidic tumor microenvironment. Additionally, under red light irradiation, the nanoconjugate generated ROS, inducing caspase-3/7-dependent apoptosis with a photo-index (PI) >50, and inhibited cancer cell migration. Our findings underscore the potential of Dox-Fe@FA-AuNPs as a highly effective and sustainable platform for targeted chemo-phototherapy.

Stepwise Ultra-pH-Sensitive Micelles Overcome a pKa Barrier for Systemic Lymph Node Delivery.

While local nanoparticle delivery to lymph nodes is well studied, there are few design criteria for intravenous delivery to the entire lymph node repertoire. In this study, we investigated the effect of NP pH transition on lymph node targeting by employing a series of ultra-pH-sensitive (UPS) polymeric micelles. The UPS library responds to pH thresholds (pKa 6.9, 6.2, and 5.3) over a range of physiological pH. We observed a dependence of intravenous lymph node targeting on micelle pH transition. UPS6.9 (subscript indicates pKa) shows poor lymph node delivery, while UPS5.3 delivers efficiently to lymph node sets. We investigated targeting mechanisms of UPS5.3, observing an accumulation among lymph node lymphatics and a dependence on lymph node-resident macrophages. To overcome the pH-threshold barrier, which limits UPS6.9, we rationally designed a nanoparticle coassembly of UPS6.9 with UPS5.3, called HyUPS. The HyUPS micelle retains the constitutive pH transitions of each polymer, showing stepwise responses to discrete pH thresholds. We demonstrate that HyUPS improves UPS6.9 delivery to lymph nodes, extending this platform for disease detection of lymph node metastasis.

Formulation of biodegradable alginate-based nano-carriers for in-vitro drug delivery and antibacterial activity.

Evaluation of the controlled release of ciprofloxacin (CIP.HCl) and the antibacterial efficacy of alginate (ALG)-based nanocarriers constitute the primary objectives of the current work. Herein, ALG-based nano-structures were prepared by the co-precipitation method and thoroughly analyzed using different characterization techniques, i.e., fourier transform infrared (FT-IR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and zeta potential (ZP). The intense peaks emerged at 500, 545, and 750 cm-1 due to the CeO bond. Peaks that appeared at 550-600 cm-1 and 525 cm-1 are due to the stretching vibrations of FeO and ZnO bonds, respectively. Lowering of the peaks from 1640 to 1630 cm-1 and 1420 to 1384 cm-1 were observed in ALG-based nanocomposite (NC) due to the interaction of ALG with metal oxides (MO), which confirmed the formulation of CeO2/ZnFe2O4/ALG nanocomposite. The diffraction peaks at 28.6°, 56.6°, 76.5°, 37°, 47.9°, 62.3°, 74°, 13°, 21° confirmed the synthesis of MO (crystallite size 15.74 nm) and CeO2/ZnFe2O4/ALG (12 nm). In accordance with morphological studies, CeO2/ZnFe2O4 oxides had a uniform distribution throughout the relatively smooth and permeable surface of the ALG-based NC. Ciprofloxacin (CIP) was used as a model drug. Negative values of ZP revealed that CIP-loaded nanocomposite (CeO2/ZnFe2O4/ALG/CIP) had more stability than CeO2/ZnFe2O4/ALG. The maximum percentage of loading around 25 % on ALG NC was examined using the optical density (OD) method at pH 5.5. Correlation coefficients from the first order (0.971), Korsmeyer (0.9858), and Hixson (0.9021) models show the best-fitted models of the release profile in all circumstances. The release mechanism was investigated using various kinetics models. The controlled drug released was observed around 17 % at 40 °C after 3 h at pH 7.4, which is almost identical to the body temperature of a human, which is 37 °C. Similarly, after 24 h, sustained and controlled in-vitro release of the drug was studied, and it was 37, 72, and 74 % at pH 2.2, 7.4, and 9.4, respectively. Thus, prepared ALG-based NC is suitable for the controlled in-vitro release of (CIP.HCl). Metal oxides (CeO2/ZnFe2O4) and ALG-based nanocomposite (CeO2/ZnFe2O4/ALG) showed great antibacterial activity against Staphylococcus aureus (S. aureus) like 15 mm and 14 mm than Escherichia coli (E. coli).

Co-axial electrosprayed RAD001-loaded polycaprolactone/polyvinyl alcohol core-shell particles for treating pediatric brain tumours.

Core-shell particles composed of polycaprolactone/polyvinyl alcohol (PCL/PVA) with pH sensitive properties were successfully fabricated by co-axial electrospraying in which PVA and PCL formed the shell and core layers respectively. The core-shell structure was confirmed by FTIR, DSC and SEM analysis. No chemical interaction between PVA and PCL core-shell were observed in the FTIR analysis. The RAD001 loaded core-shell particles showed a sustained and pH dependent drug release and was assayed via our previously developed HPLC method. After indirect treatment of the PF-A cells with the core-shell particles for 24 h and 5 days a decrease in cell viability was observed. Additionally, a comparison was made with our previously developed nanoparticles containing 2 %PVA-14 %SOL®-0.6 % RAD001, for the cell viability study on ependymoma. Our findings show that optimised core-shell particles exerted a significant effect for the 24 h and 5 day treatment however further studies are required to ensure toxicity of the control core-shell particles with no drug is reduced. In comparison, the 2 %PVA-14 %SOL®-0.6 %RAD001 uniaxial electrosprayed nanoparticles also exerted a toxicity effect decreasing cell viability with no toxicity observed for the control nanoparticles as well. Such pH-sensitive core-shell particles, which can degrade effectively in either acidic or neutral condition, have great potential for application in the biomedical field.

A Triterpene-Based bioactive drug delivery system for combined chemotherapy of liver cancer.

Carrier materials always account for the majority particularly in nanosized formulations, which are administrated along with the active ingredient part might result in metabolism related toxicity. The usage of bioactive excipients could not only reduce the sided effect but also provide additional therapeutic effects. In the present study, a triterpene based micellar drug delivery system was developed using a bioactive solanesol derivative. Solanesylamine was prepared firstly followed by conjugating with poly (ethylene glycol) using maleic acid amide linkage. The amphiphilic drug carrier PEGylated (2-propyl-3-methylmaleic acid)-block-solanesol amine (mPEG-CDM-NH-SOL) could be formed into micelles and loaded with doxorubicin (DOX) inside. The micelles were about 112 nm in size and the drug loading content was about 5.97 wt%. An acid triggered drug release behavior was obviously observed for the DOX loaded pH-sensitive micelle mPEG-CDM-NH-SOL-DOX. While not for DOX-loaded micelles without pH-sensitivity (mPEG-NHS-NH-SOL). CCK8 assay showed that the micelles of PEGylated solanesylamines exhibited certain inhibitory effect on tumor cells at high concentration and the pH sensitive ones seemed more toxic. In vivo studies showed that the pH sensitive mPEG-CDM-NH-SOL-DOX had a superior anti-tumor effect, indicating its great potential in cancer treatment.

Biofilms from poly-vinyl alcohol/palmyra root sprout with Boswellia serrata, carbon dots and anthocyanin for sensing the freshness of sardine fish.

One of the main issues that customers worldwide have is food adulteration. In commercial packages, freshness cannot always be determined visually. Here, we propose sensitive films for use in food packaging that could alter colour to indicate a change in freshness. Hybrid, multifunctional, and eco-friendly films were prepared from polyvinyl alcohol/palmyra root sprout (PVA/PRS), fused with soy protein isolate carbon dot (CD), Boswellia serrata (BS), and Clitoriaternatea anthocyanin (CTE). The films showed pH sensitivity, antioxidant, and UV barrier properties. By creating hydrogen bonds between PRS and the other fillers, adding these substances makes PVA less crystallized. These interactions were verified by infrared Fourier-transform analysis. When compared to PVA, PRS films had significantly lower moisture content and swelling ratios. The UV-blocking capabilities of the films were greatly improved by the addition of CD, BS, and CTE without compromising their mechanical, thermal, or water vapor barrier properties. The composite film PVA/PRS/CD/BS/CTE exhibited a maximum tensile strength value of 69.47 ± 1.49 MPa. The CT extract provides the film with superior antioxidant properties. The colorimetric films PVA/PRS/CTE and PVA/PRS/CD/BS/CTE showed distinct pH-responsive colour-change properties as well as good colour stability. The colorimetric films were used to test the freshness of sardine fish, and they revealed unique colour changes that indicated whether the fish sample was spoiled or not.

Synthesis, characterization and stability of crosslinked chitosan-maltodextrin pH-sensitive nanogels.

Polysaccharide-based nanogels offer a wide range of chemical compositions and are of great interest due to their biodegradability, biocompatibility, non-toxicity, and their ability to display pH, temperature, or enzymatic response. In this work, we synthesized monodisperse and tunable pH-sensitive nanogels by crosslinking, through reductive amination, chitosan and partially oxidized maltodextrins, by keeping the concentration of chitosan around the overlap concentration, i.e. in the dilute and semi-dilute regime. The chitosan/maltodextrin nanogels presented sizes ranging from 63 ±â€¯9 to 279 ±â€¯16 nm, showed quasi-spherical and cauliflower-like morphology, reached a ζ-potential of +36 ±â€¯2 mV and maintained a colloidal stability for up to 7 weeks. It was found that the size and surface charge of nanogels depended both on the oxidation degree of maltodextrins and chitosan concentration, as well as on its degree of acetylation and protonation, the latter tuned by pH. The pH-responsiveness of the nanogels was evidenced by an increased size, owed to swelling, and ζ-potential when pH was lowered. Finally, maltodextrin-chitosan biocompatible nanogels were assessed by cell viability assay performed using the HEK293T cell line.

PH-sensitive BSA-modified resveratrol micelles targeting macrophages alleviate symptoms of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, leading to severe inflammatory infiltration and joint damage, accompanied by a decrease in pH of joint microenvironment. Macrophages play an important role in the pathogenesis of RA, with high expression of bovine serum albumin (BSA) receptors on the surface of macrophages. Resveratrol (Res) has strong anti-inflammatory effects, but its application is limited due to its poor water solubility and low bioavailability. Therefore, we constructed pH-sensitive micelles by encapsulating Res and modifying BSA on the surface of the micelles (BSA-Res@Ms), thereby greatly improving the therapeutic effect of RA. Our research results indicated that BSA-Res@Ms had a smooth and uniform appearance, small particle size, high drug encapsulation efficiency, good stability, and pH-sensitive properties. In vitro, BSA-Res@Ms increased the uptake of Res by RAW264.7 cells, reduced the levels of pro-inflammatory cytokines and cleared excess ROS produced by activated RAW264.7 cells, and inhibited the generation of osteoclasts. In vivo, BSA-Res@Ms could target inflamed joint sites, significantly alleviate joint inflammation symptoms, inhibit activated macrophages, improve synovial hyperplasia and inflammatory cell infiltration, and protect cartilage. BSA-Res@Ms provide a very promising method for the treatment of RA, which can effectively improve the inflammatory manifestations of RA.

Enzymatically green-produced bacterial cellulose nanoparticle-stabilized Pickering emulsion for enhancing anthocyanin colorimetric performance of versatile films.

To enhance the colorimetric performance of anthocyanin (Ant), a konjac glucomannan (KGM)-based multifunctional pH-responsive indicator film was fabricated by introducing enzymatically prepared bacterial nanocellulose (EBNC) stabilized camellia oil/camellia essential oil Pickering emulsion (BCCE). Specifically, optimized enzymatic hydrolysis time (36 h) was determined based on the particle size and microstructure. Then BCCE (containing 0.4% EBNC) was incorporated into Ant-containing KGM, and the novel active indicator film (KGM-Ant-BCCE) was constructed. Films with varying BCCE concentrations (3%-11%) exhibited enhanced UV shielding, thermal stability, mechanical strength, water vapor and oxygen permeability, hydrophobicity, and antioxidant performance. The pronounced color change of KGM-Ant-BCCE indicated its potential for visually detecting shrimp freshness. Moreover, the biodegradability (25 days) confirmed the environmentally benign property of the film. In summary, incorporating green-produced EBNC nanoparticle-stabilized BCCE offers an innovative pathway to improve the color indication capability of polysaccharide-based smart packaging.

Matrix Metalloproteinase- and pH-Sensitive Nanoparticle System Enhances Drug Retention and Penetration in Glioblastoma.

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.

Microenvironment Responsive Hydrogel Exerting Inhibition of Cascade Immune Activation and Elimination of Synovial Fibroblasts for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a progressive autoimmune disease and drug therapy has been restricted due to poor therapeutic efficacy and adverse effects. In RA synovium, dendritic cells present self-antigens to activate cascade immune pathway. Furthermore, downstream macrophages secrete high levels of pro-inflammatory cytokines; Hyperplasia of activated synovial fibroblasts (FLS) is responsible for hypoxic synovium microenvironment, secretion of cytokines/chemokines and erosion of bone/cartilage tissues. Positive feedback loop of inflammation between macrophages and FLS independent of antigen-presentation is constructed. Herein, an injectable pH-sensitive peptide hydrogel encapsulating siRNA/Methotrexate-polyethyleneimine (siMP, including sip65MP, sip38MP, siCD86MP) and Bismuthene nanosheet/Methotrexate-polyethyleneimine (BiMP) is successfully developed. Among them, siCD86MP reduces protein level of co-stimulatory molecule CD86 while sip65MP and sip38MP separately inhibit NF-κB and MAPK-p38 pathways of macrophages and FLS to suppress secretion of cytokines and MMPs. Meanwhile, reduction in anti-apoptotic property of FLS induced by inhibition of NF-κB pathway has a synergistic effect with photodynamic therapy (PDT) and photothermal therapy (PTT) mediated by BiMP for FLS elimination, effectively ameliorating hypoxic synovium microenvironment. After being injected into synovium, hydrogel responds to acidic microenvironment and serves as a reservoir for sustained drug release and inherent retention capacity of which enables cationic nanoparticles to bypass tissue barrier for precise synovium targeting. This brand-new drug delivery system combines modulating cascade immune pathway from beginning to end by RNAi and eliminating FLS for improving synovium microenvironment by phototherapy together, providing a robust strategy for clinical RA treatment.

Colloidal and Biological Characterization of Dual Drug-Loaded Smart Micellar Systems.

Smart polymeric micelles (PMs) are of great interest in drug delivery owing to their low critical micellar concentration and sizes. In the present study, two different pH-sensitive poly(2-vinyl pyridine)-b-poly(ethylene oxide) (P2VP-b-PEO) copolymer samples were used for the encapsulation of paclitaxel (PTX), ursolic acid (UA), and dual loading of PTX and UA. Based on the molecular features of copolymers, spherical PMs with sizes of around 35 nm and 140 nm were obtained by dialysis for P2VP55-b-PEO284 and P2VP274-b-PEO1406 samples, respectively. The micellar sizes increased after loading of both drugs. Moreover, drug encapsulation and loading efficiencies varied from 53 to 94% and from 3.2 to 18.7% as a function of the copolymer/drug ratio, molar mass of copolymer sample, and drug type. By FT-IR spectroscopy, it was possible to demonstrate the drug loading and the presence of some interactions between the polymer matrix and loaded drugs. In vitro viability was studied on 4T1 mammary carcinoma mouse cells as a function of time and concentration of drug-loaded PMs. UA-PMs and free PMs alone were not effective in inhibiting the tumor cell growth whereas a viability of 40% was determined for cells treated with both PTX- and PTX/UA-loaded PMs. A synergic effect was noticed for PTX/UA-loaded PMs.