pH Sensitivity Research Articles

A series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structure for drugs delivery systems of paclitaxel: Synthesis, structure-activity relationship and anti-tumors effect

Aggregation-induced emission (AIE) materials are attracting great attention in biomedical fields such as sensors, bioimaging, and cancer treatment, et al. due to their strong fluorescence emission in the aggregated state. In this contribution, a series of tetraphenylene-acetonitrile AIE compounds with D-A-D′ structures were synthesized by Suzuki coupling reaction and Knoevenagel condensation, and their relationship of chemical structure and fluorescence properties was investigated in detail, among which TPPA compound was selected as the monomer owing to the longest emission wavelength at about 530 nm with low energy band gap ΔE 3.09 eV of neutral TPPA and 1.43 eV of protonated TPPA. Novel amphiphilic AIE PEG-TA copolymers were prepared by RAFT polymerization of TPPA and PEGMA with about 1.44×104 Mw and narrow PDI, and the molar ratio of TPPA in the PEG-TA1 and PEG-TA2 copolymers was about 23.4 % and 29.6 %. The as-prepared PEG-TA copolymers would self-assembled in aqueous solution to form core-shell structures with a diameter of 150–200 nm, and their emission wavelength could reversibly convert from 545 nm to 650 nm with excellent pH sensitivity. The CLSM images showed that the PEG-TA FONs and PTX drugs-loaded PTX-TA FONs could be endocytosed by cells and mainly enriched in the cytoplasm, and CCK-8 results showed that the PEG-TA FONs had excellent biocompatibility but PTX-TA FONs had high inhibition ratio for A549 cells, moreover, the flow cytometry also showed that PTX-TA FONs could result in the apoptosis of A549 cells with some extent anti-tumor effect.

Synthesis and characterization of oleic acid-stabilized cobalt ferrite @MCM-41/nanocomposites for pH-responsive drug delivery

This study presents composite nanoparticles combining cobalt ferrites-oleic acid (CF-OA) and mesoporous silica (MCM-41) for drug delivery. Temperature-dependent analyses at 25 and 42 °C reveal distinct alterations in particle size and distribution, emphasizing the role of oleate complexes in stabilizing the nanocomposites. Power of Laws calculations (n = 0.58, m = 0.44) assessed diffusion and matrix erosion effects, highlighting the pH-responsive behavior. Results showed CF-OA@MCM-41with nanometric scale and predominantly spherical morphology influenced by temperature variations. Nitrogen BET analysis revealed a surface area of 542.1 m2g−1 and a pore volume of 1.1 cm3g−1. Drug release studies demonstrated controlled doxorubicin (DOX) release from CF-OA@MCM-41. In vivo studies showed significant tumor growth suppression (liver cancer): average tumor volume in D-C@M group was 167.8 mm3 after 21 days, compared to 1953.8 mm3, 1203.6 mm3, and 269 mm3 for PBS, CF-OA@MCM-41, and DOX alone respectively. In vitro, a 3 µg mL−1 concentration showed no significant 293 T cell viability change and increased HEP G2 cell viability. Significant HEP G2 cell viability inhibition occurred at 1 and 2 µg mL−1 CF-OA@MCM-41 carrying DOX, with p-values < 0.01 and < 0.001. CF-OA@MCM-41 nanoparticles exhibit promising potential for targeted cancer therapy due to their pH sensitivity and controlled drug release capabilities.

Synergistic Photothermal Tumor Immunotherapy by 1-MT Based on Zeolitic Imidazolate Framework-8 with pH-High Sensitivity.

A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT). In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy. MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response. The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.

PH-Sensitive Fluorescent Marker Based on Rhodamine 6G Conjugate with Its FRET/PeT Pair in "Smart" Polymeric Micelles for Selective Imaging of Cancer Cells.

Cancer cells are known to create an acidic microenvironment (the Warburg effect). At the same time, fluorescent dyes can be sensitive to pH, showing a sharp increase or decrease in fluorescence depending on pH. However, modern applications, such as confocal laser scanning microscopy (CLSM), set additional requirements for such fluorescent markers to be of practical use, namely, high quantum yield, low bleaching, minimal quenching in the cell environment, and minimal overlap with auto-fluorophores. R6G could be the perfect match for these requirements, but its fluorescence is not pH-dependent. We have attempted to develop an R6G conjugate with its FRET or PeT pair that would grant it pH sensitivity in the desired range (5.5-7.5) and enable the selective targeting of tumor cells, thus improving CLSM imaging. Covalent conjugation of R6G with NBD using a spermidine (spd) linker produced a pH-sensitive FRET effect but within the pH range of 7.0-9.0. Shifting this effect to the target pH range of 5.5-7.5 appeared possible by incorporating the R6G-spd-NBD conjugate within a "smart" polymeric micelle based on chitosan grafted with lipoic acid. In our previous studies, one could conclude that the polycationic properties of chitosan could make this pH shift possible. As a result, the micellar form of the NBD-spd-R6G fluorophore demonstrates a sharp ignition of fluorescence by 40%per1 pH unit in the pH range from 7.5 to 5. Additionally, "smart" polymeric micelles based on chitosan allow the label to selectively target tumor cells. Due to the pH sensitivity of the fluorophore NBD-spd-R6G and the selective targeting of cancer cells, the efficient visualization of A875 and K562 cells was achieved. CLSM imaging showed that the dye actively penetrates cancer cells (A875 and K562), while minimal accumulation and low fluorophore emission are observed in normal cells (HEK293T). It is noteworthy that by using "smart" polymeric micelles based on polyelectrolytes of different charges and structures, we create the possibility of regulating the pH dependence of the fluorescence in the desired interval, which means that these "smart" polymeric micelles can be applied to the visualization of a variety of cell types, organelles, and other structures.

Exploring the Therapeutic Potential of 5-Fluorouracil-Loaded Calcium Carbonate Nanoparticles Combined with Natural Compound Thymoquinone for Colon Cancer Treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO3np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO3np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO3np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO3np (1.875 μM) and TQ (30 μM) showed significantly superior anti-colon cancer effects to 5FU-CaCO3np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO3np as a novel regimen against colon cancer. Combining 5FU-CaCO3np and TQ may offer a new perspective for colon cancer therapy.

Hydrothermally synthesized Al-doped β-Ga2O3 microrods for enhanced pH sensing performance

In our study, Al-doped β-Ga2O3 microrods were deposited on FTO glass substrate via hydrothermal method followed by calcination at 700 °C for 3 h. The Al-doped β-Ga2O3 microrods were characterized using XRD, SEM, XPS, and FTIR spectroscopy techniques. The intrinsic β-Ga2O3 extended-gate field-effect transistor (EGFET)-based pH sensor exhibited a pH sensitivity of 57.29 mV/pH with 99.34 % linearity within the pH range of 3–11. Conversely, the Al-doped β-Ga2O3 EGFET-pH sensor, containing 0.52 at. % of Al, demonstrated an elevated pH sensitivity of 77.63 mV/pH with 99.17 % linearity. Our findings indicate that the incorporation of Al enhances the pH sensing capabilities of β-Ga2O3 microrods to the presence of additional binding sites facilitated by its improved specific surface area. Remarkably, even a minute amount (0.52 at. %) of Al doping in β-Ga2O3 suffices to significantly improve the performance of pH sensing. These results underscore the potential of Al-doped β-Ga2O3 as a promising material for development of high-performance ion or biosensors.

Polymeric pH-Responsive Metal-Supramolecular Nanoparticles for Synergistic Chemo-Photothermal Therapy.

Stimuli-responsive drug delivery carriers, particularly those exhibiting pH sensitivity, have attracted significant scholarly interest due to their promising potential in anticancer therapeutic applications. This phenomenon can primarily be ascribed to the inherently acidic nature of tumor microenvironments. However, pH-responsive carriers frequently require the incorporation of functional groups or materials sensitive to pH changes. Given the pH-sensitive characteristics of metal coordination with natural small-molecule drugs, organometallic supramolecules present a facile and effective strategy for integrating pH-responsive behavior into these systems. Meanwhile, utilizing the natural compound luteolin in conjunction with iron ions (Fe3+) through the advanced engineering technique of flash nanoprecipitation (FNP) results in the synthesis of stable, highly loaded nanoparticles (NPs) exhibiting a supramolecular photothermal effect. Our experimental findings substantiate that the photothermal effect persists over time, even after the pH-responsive release phase has ended. Consequently, these polymeric pH-responsive metallic supramolecular nanoparticles integrate chemotherapy and photothermal therapy, creating a synergistic approach to cancer treatment. This bifunctional platform, which exhibits both pH-responsive and photothermal properties, presents a highly promising avenue for biomedical applications, particularly in the area of tumor therapies. Its dual function offers a potentially efficacious approach to tumor treatment.

Crosslinking and Swelling Properties of pH-Responsive Poly(Ethylene Glycol)/Poly(Acrylic Acid) Interpenetrating Polymer Network Hydrogels.

This study investigates the crosslinking dynamics and swelling properties of pH-responsive poly(ethylene glycol) (PEG)/poly(acrylic acid) (PAA) interpenetrating polymer network (IPN) hydrogels. These hydrogels feature denser crosslinked networks compared to PEG single network (SN) hydrogels. Fabrication involved a two-step UV curing process: First, forming PEG-SN hydrogels using poly(ethylene glycol) diacrylate (PEGDA) through UV-induced free radical polymerization and crosslinking reactions, then immersing them in PAA solutions with two different molar ratios of acrylic acid (AA) monomer and poly(ethylene glycol) dimethacrylate (PEGDMA) crosslinker. A subsequent UV curing step created PAA networks within the pre-fabricated PEG hydrogels. The incorporation of AA with ionizable functional groups imparted pH sensitivity to the hydrogels, allowing the swelling ratio to respond to environmental pH changes. Rheological analysis showed that PEG/PAA IPN hydrogels had a higher storage modulus (G') than PEG-SN hydrogels, with PEG/PAA-IPN5 exhibiting the highest modulus. Thermal analysis via thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) indicated increased thermal stability for PEG/PAA-IPN5 compared to PEG/PAA-IPN1, due to higher crosslinking density from increased PEGDMA content. Consistent with the storage modulus trend, PEG/PAA-IPN hydrogels demonstrated superior mechanical properties compared to PEG-SN hydrogels. The tighter network structure led to reduced water uptake and a higher gel modulus in swollen IPN hydrogels, attributed to the increased density of active network strands. Below the pKa (4.3) of acrylic acid, hydrogen bonds between PEG and PAA chains caused the IPN hydrogels to contract. Above the pKa, ionization of PAA chains induced electrostatic repulsion and osmotic forces, increasing water absorption. Adjusting the crosslinking density of the PAA network enabled fine-tuning of the IPN hydrogels' properties, allowing comprehensive comparison of single network and IPN characteristics.

Tracking the enzyme-response mechanism of tannic acid-embedded chitosan/γ-polyglutamic acid hydrogel

The design of enzyme-response hydrogels has attracted increasing interest in cell therapy, biomedical research, and tissue engineering. Their rational design usually depends on the enzyme-response mechanism and have focused on behavior improvement, drug delivery, and state transition of hydrogels. However, no enzyme-response mechanism has yet been systematically investigated. Here, we construct a tunable platform of tannic acid-embedded chitosan/γ-polyglutamic acid hydrogel to study the enzyme-response mechanism. We track the roles of gallic acid hydrolyzed from tannic acid in altering the structure and properties of the hydrogel to get insights into the mechanism. The gallic acid inside the hydrogel enhances hydrogel crosslinking, increasing the mechanical properties and pH sensitivity but reducing thickness, porosity, and swelling behavior. The gallic acid outside the hydrogel increases the positive potential and superficial hydrophobicity of the hydrogel. These findings will aid the rational design of other enzyme-response hydrogels in more extensive self-adaptive fields.

High‐performance aminosilane‐infused alginate capsules for sustained drug release

AbstractSodium alginate (AlgNa) is often used to prepare oral drug capsules, offering the advantages of facile carrier formation and pH sensitivity. However, these capsules suffer from high porosity, large pore size, and mechanical and physiological instabilities. Although the performance of AlgNa in oral drug carriers can be enhanced through hybridization with other substances, this results in increased complexity and additional preparation steps. To address this problem, organic–inorganic hybrid capsules are herein prepared via the one‐step incorporation of aminosilanes (3‐aminopropyltriethoxysilane and 3‐(2‐aminoethylamino)propyltrimethoxysilane) into AlgNa and evaluated as delivery vehicles for the sustained release of a model drug, diclofenac sodium. The hybrid capsules show elevated drug encapsulation efficiencies (up to 92.7%) and pH responsiveness and outperform pure alginate capsules, exhibiting contraction and low release rates (&lt;10%) in a simulated stomach environment (pH 1.2) and swelling and sustained release (10 h) in a simulated intestinal environment (pH 7.4). The formation of siloxane bonds between the aminosilane molecules results in stronger and more compact capsule membranes contributing to sustained drug release. Thus, our results demonstrate the potential of the proposed capsules, fabricated using a simple ecofriendly method, as carriers for sustained drug release.

PH Sensitivity of YFPs is Reduced Upon AlphaRep Binding: Proof of Concept in Vitro and in Living Cells.

Yellow fluorescent proteins (YFPs) are commonly used in biology to track cellular processes, particularly as acceptors in experiments using the Förster Resonant Energy Transfer (FRET) phenomenon. However, their fluorescence intensity is strongly pH-dependent, limiting their utility in acidic environments. Here, we explore the pH sensitivity of YFPs upon binding with an artificial repeat protein (αRep) both in vitro and in living cells. We show that αRep binds to Citrine, with high affinity in the nanomolar range at physiological and acidic pHs, leading to increased thermal stability of the complex. Moreover, αRep binding reduces Citrine's pKa by 0.75 pH units, leading to a decreased sensitivity to pH fluctuations. This effect can be generalized to other YFPs as Venus and EYFP in vitro. An efficient binding of αRep to Citrine has also been observed in living cells both at pH 7.4 and pH 6. This interaction leads to reduced variations of Citrine fluorescence intensity in response to pH variations in cells. Overall, the study highlights the potential of αReps as a tool to modulate the pH sensitivity of YFPs, paving the way for future exploration of biological events in acidic environments by FRET in combination with a pH-insensitive cyan donor.

Intelligent Food Packaging: Quaternary Ammonium Chitosan/Gelatin Blended Films Enriched with Blueberry Anthocyanin-Derived Cyanidin for Shrimp and Milk Freshness Monitoring.

Blueberry anthocyanin-derived cyanidin (BAC) was used to prepare a series of responsive food freshness packaging films by compounding it with quaternary chitosan (QC) and gelatin (G). The fundamental properties, pH sensitivity, and functional attributes of the films were examined. The BAC solutions exhibited notable variations in color (from red to pink to violet) under different pH conditions. The incorporation of BAC resulted in improved UV-vis shielding capabilities but compromised the mechanical strength of the films (with tensile strength values from 85.02 to 44.89 MPa, elongation at break from 13.08% to 3.6%, and water vapor transmission rates from 5.24 × 10-9 to 7.80 × 10-9 g m-1 s-1 Pa-1). The QC-G-BAC films, containing 5-15 wt% BAC, exhibited noticeable color changes in acidic/ammonia environments within a short timeframe, easily discernible to the naked eye. Furthermore, the inclusion of BAC significantly enhanced the antioxidant and antimicrobial properties of the films. The addition of 5-15 wt% BAC to QC-G-BAC films could be employed for assessing the freshness of fresh shrimp (from red to dark red) and pasteurized milk (from red to dark earthy yellow). Among them, the total color difference (ΔE) of QC-G-BAC5 film was significantly correlated with the pH, acidity, and total colony count of pasteurized milk (R = 0.846, -0.930, -0.908, respectively). This new concept in smart packaging offers a straightforward and user-friendly freshness indicator.

Improved release of sulfamethoxazole from electrospun water soluble fibers

Electrospun fibers containing an active component, sulfamethoxazole, were successfully prepared from three water-soluble polymers, poly(vinyl pyrrolidone) (PVP), poly(vinyl alcohol) (PVA) and hydroxypropyl methylcellulose (HPMC). The conditions of electrospinning had to be optimized individually for the three systems. The presence of the drug did not influence fiber characteristics significantly, the diameter of the fibers increased only slightly upon the addition of the drug. Detailed investigations proved that the drug is located within the fibers in the amorphous form facilitating release. The strong pH sensitivity of the dissolution of the drug decreased considerably by encapsulation into the fibers. Drug release from the fibers is much faster than the dissolution of the neat drug and the relative amount of dissolved drug is also considerably larger (95 % vs. 30 %) from fibers encapsulating it. PVP seems to be the best selection for the preparation of electrospun fibers containing sulfamethoxazole, encapsulation is the largest (90.1 %) and drug release is the fastest from it among the three polymers. The preparation of formulations from sulfamethoxazole by electrospinning is clearly beneficial and must increase the bioavailability of this BCS IV drug.

A pH-sensitive film based on chitosan/gelatin and anthocyanin from Zingiber striolatum Diels for monitoring fish freshness

As a new type of packaging method, the anthocyanin-based pH-sensitive indicator film has gained much attention owing to low cost, small size, and visually informative property. In this study, an intelligent film based on chitosan/gelatin (CG) matrix with Zingiber striolatum Diels (ZSD) anthocyanin for fish freshness monitoring was developed. The film properties, including thickness, moisture content, color, mechanical properties, UV–vis light barrier property, as well as pH and ammonia sensitivity, were evaluated. The CG-ZSD films exhibited a more compact structure when compared with the CG film. The CG-ZSD20 film showed the highest elongation at break (6.33 ± 0.62%) and lowest tensile strength (20.0 ± 0.58 MPa). FTIR spectra revealed the strong hydrogen bond interactions between ZSD and polymer matrix. Film incorporated with 15% anthocyanin extract has increased melting temperature at 118.9 °C, and a lower weight loss (13.8%) at melting temperature. In pH 1–14 buffer, the color of CG-ZSD films underwent a significant change from red to yellow-green. The CG-ZSD15 film was utilized for monitoring fish freshness and showed visible color changes from deep purple to brown. The total volatile basic nitrogen content and pH value changes of fish were closely related to the visual color changes in film. This demonstrated that the film was a highly pH-sensitive film for quantifying fish freshness in real-time.

A cascade SPR sensor based on Ag/Au coated coreless optical fiber for RI and pH measurement

Due to the restriction of resonant wavelength, the detection range of traditional two-parameter sensors is greatly limited. To solve this problem, a cascade SPR sensor with Ag/Au coating is proposed to measure refractive index (RI) and pH value. In this paper, coreless optical fiber is used as the sensor probe, and Ag/Au are coated on its surface by a magnetron sputtering method. The two sensing channels of this cascade sensor are independent of each other and have a wide parameter detection range. The effects of sensor length and coating time on the performance of the sensor were investigated, and the optimal sensor length and coating time were determined. The experimental results show that the maximum refractive index sensitivity is 3888.6 nm /RIU in the RI range of 1.333–1.385, and the maximum pH sensitivity is 38.01 nm/pH in the pH range of 3.15–8.86. The sensor has the advantages of strong stability and high integration and has a good application prospect in the fields of biosensing and environmental detection.

Flexible and Disposable Hafnium Nitride Extended Gates Fabricated by Low-Temperature High-Power Impulse Magnetron Sputtering.

To obtain a high-performance extended gate field-effect transistor for pH detection, hafnium nitride (HfN) was first fabricated on an indium tin oxide on polyethylene terephthalate (ITO/PET) substrate using a high-power impulse magnetron sputter system (HiPIMS) in this study. It can be easily applied in biomedical diagnostic and environmental monitoring applications with the advantages of flexible, disposable, cost-effective, and reliable components. Various duty cycle conditions in HiPIMSs were designed to investigate the corresponding sensing performance and material properties including surface morphology and composition. As the duty cycle increased, the grain size of HfN increased. Additionally, X-ray photoelectron spectroscopy (XPS) analysis illustrated the presence of HfOxNy on the deposited HfN surface. Both behaviors could result in a better pH sensing performance based on the theory of the site-binding model. Subsequently, HfN with a 15% duty cycle exhibited excellent pH sensitivity and linearity, with values of 59.3 mV/pH and 99.8%, respectively; its hysteresis width and drift coefficient were -1 mV and 0.5 mV/h, respectively. Furthermore, this pH-sensing performance remained stable even after 2000 repeated bending cycles. These results indicate the potential and feasibility of this HiPIMS-deposited HfN for future wearable chemical applications.

Bovine serum albumin-coated ZIF-8 nanoparticles to enhance antitumor and antimetastatic activity of methotrexate: in vitro and in vivo study

In this study, a bovine serum albumin-decorated zeolitic imidazolate framework (ZIF-8@BSA) was used to enhance the anticancer and antimetastatic properties of methotrexate. SEM, DLS, FT-IR, and XRD confirmed the physicochemical suitability of the developed nanoparticles. According to the SEM analysis, the mean size of ZIF-8 nanoparticles was 68.5 ± 13.31 nm. The loading capacity and encapsulation efficiency of MTX@ZIF-8@BSA were 28.77 ± 2.54% and 96.3 ± 0.67%, respectively. According to the in vitro hemolysis test, MTX@ZIF-8@BSA showed excellent blood compatibility. MTX@ZIF-8@BSA exhibited pH sensitivity, releasing more MTX at pH 5.4 (1.73 times) than at pH 7.4. The IC50 value of MTX@ZIF-8@BSA on 4T1 cells was 32.7 ± 7.3 µg/mL after 48 h of treatment, outperforming compared to free MTX with an IC50 value of 53.3 ± 3.7 µg/mL. Treatment with MTX@ZIF-8@BSA resulted in superior tumor growth suppression in tumor-bearing mice than free MTX. Furthermore, based on histopathology tests, MTX@ZIF-8@BSA reduced the metastasis in lung and liver tissues. While there was not any noticeable toxicity in the vital organs of MTX@ZIF-8@BSA-receiving mice, free methotrexate resulted in severe toxicity in the kidneys and liver. According to the preliminary in vitro and in vivo findings, MTX@ZIF-8@BSA presents an attractive drug delivery system candidate for breast cancer due to its enhanced antitumor efficacy and lower toxicity.

Gelatin-nanocellulose stabilized emulsion-filled hydrogel beads loaded with curcumin: Preparation, encapsulation and release behavior

In this study, the curcumin was firstly encapsulated in gelatin (GLT) and/or cellulose nanocrystals (CNC) stabilized emulsions, then further mixed with sodium alginate (SA) to form emulsion-filled hydrogel beads loaded with curcumin (Cur). The Cur-loaded emulsions showed a droplet size of 20.3–24.4 μm with a uniform distribution. Introducing CNC and/or SA increased the viscosity of emulsions accompanied by viscoelastic transition, while the modulus was reduced due to destruction of GLT gel. Cur was doubly immobilized in the hydrogel beads with >90 % of encapsulation efficiency. The results of simulated gastrointestinal tract experiments revealed that the beads possessed a good pH sensitivity and controlled release behavior to prolong the retention of Cur in the gastrointestinal tract. After 6 h of UV irradiation, the Cur-loaded emulsion-filled hydrogel beads showed a higher antioxidant activity than that of pure Cur, effectively delaying the photodegradation of Cur. In addition, the beads had better stability in aqueous and acidic environments, which was favorable for prolonging the release of Cur. These results suggest that the emulsion-filled hydrogel beads have great potential for the delivery of lipophilic bioactive molecules.

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 ± 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.

Delivery of piperlongumine via hyaluronic acid/phenylboronic acid-mediated dual targetable polymersome for enhanced anticancer functionality against pancreatic tumor

Pancreatic cancer cells highly resistance to conventional chemo drugs, resulting low survival rates. The aim of the study was to design and develop dual targeting polymersomes (DTPS) loaded with phyto alkaloid agent i.e., piperlongumine (PL) for effective pancreatic cancer treatment. Here, hyaluronic acid (HA) was functionalized with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG-NH2), poly(ethylene glycol) bis (amine) (PEG), and phenylboronic acid (PBA) moieties. The designed DTPS could selectively recognize CD44/sialic acid (SA) and deliver PL to MIA PaCa-2 pancreatic cancer cells, facilitated via HA-CD44 and PBA-SA interactions. Drug release and stability results implied sustained PL release profile and pH sensitivity. DTPS could be more efficiently bound with SA than other sugars based on fluorescence spectroscopy. The anticancer efficacy of designed polymersomes was tested with H6C7 normal pancreas cells and SA/CD44-overexpressed MIA PaCa-2 pancreatic cancer cells. DTPS showed both SA and CD44-mediated higher cellular uptake while single-targeted polymersomes showed CD44-mediated cellular uptake. The PL-loaded DTPS efficiently uptake by MIA PaCa-2 cancer cells, causing up to 80 % cell growth inhibition, reduced cell spheroids volume and increased dead cells by 58.3 %. These results indicate that the newly developed DTPS can effectively serve as a pH-responsive drug delivery system for efficient treatment of cancer.