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The challenge of multispecies bacterial biofilms involves secondary infections from biofilm dispersion while failing to clear resident‐bacteria, along with health risks from endotoxins. Although photodynamic therapy simultaneously eliminates biofilms and resident‐bacteria, its effectiveness is limited by the short half‐life of reactive oxygen species (ROS). And the slightly acidic properties of biofilms offer opportunities to mitigate anionic endotoxin hazards. Consequently, a nanoproducer is developed that releases nitric oxide by leveraging its prolonged half‐life and interaction with superoxide anions to extend the range of ROS oxidation. Meanwhile, the nanoproducer can respond to the biofilm's pH, gaining a strong positive charge to effectively capture released endotoxin during treatment. This research indicates that nanoproducers effectively disperse biofilms and improve their penetration into polymeric substances, leading to efficient reduction of bacterial burden in mice harboring biofilm and abscess models. Additionally, nanoproducers effectively reduce inflammatory cytokine levels and immune cell infiltration caused by endotoxin. The nanoplatform, therefore, demonstrates remarkable promise in combating bacterial biofilm infections and alleviating the risks associated with endotoxins. [ABSTRACT FROM AUTHOR]

Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNPN caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment. [Display omitted] • pH sensitive and pH non-sensitive redox nanoparticles (RNPN and RNPO, respectively) were developed and effectively scavenged various reactive oxygen species; • Orally admistered RNPN exhibited higher gastric accumulation and retention compared to RNPO; • Both RNPs, especially RNPN, showed a significantly protective effects in aspirin-induced gastric ulcer via oral administration; • Both RNPs exhibited extremely low toxicity in zebrafish embryos compared to control polymeric nanoparticles (without ROS scavenging moieties). [ABSTRACT FROM AUTHOR]

Background: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. Methods: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box–Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. Results: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. Conclusions: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen. [ABSTRACT FROM AUTHOR]

This study aimed to develop paclitaxel (PTX)-loaded PEGylated (PEG)-pH-sensitive (SpH) liposomes to enhance drug delivery efficiency and cytotoxicity against MCF-7 breast cancer cells. PTX-loaded PEG-SpH liposomes were prepared using the thin film hydration method. ATR-FTIR compatibility studies revealed no significant interactions among liposome formulation components. TEM images confirmed spherical morphology, stability, and an ideal size range (180–200 nm) for improved blood circulation. At pH 5.5, liposomes exhibited increased size and positive zeta potential, indicating pH-sensitive properties due to CHEMS response to the acidic tumor microenvironment. Conversely, at pH 7.4, liposomes showed a slightly larger size (199.25 ± 1.64 nm) and a more negative zeta potential (-36.94 ± 0.32 mV), suggesting successful PEG-SpH surface modification, enhancing stability, and reducing aggregation. PTX-loaded PEG-SpH liposomes demonstrated high encapsulation efficiency (84.57 ± 0.92% w/w) and drug loading capacity (4.12 ± 0.26% w/w). In-vitro drug release studies revealed accelerated first-order PTX release at pH 5.5 and a controlled zero-order release at pH 7.4. Cellular uptake studies on MCF-7 cells demonstrated enhanced PTX uptake, attributed to mPEG-PCL incorporation prolonging circulation time and CHEMS facilitating PTX release in the tumor microenvironment. Furthermore, PTX-loaded PEG-SpH liposomes exhibited significantly improved cytotoxicity with an IC50 value of 1.107 µM after 72-h incubation, approximately 90% lower than plain PTX solution. Stability studies confirmed the robustness of the liposomal formulation under various storage conditions. These findings highlight the potential of PEGylated pH-responsive liposomes as effective nanocarriers for enhancing PTX therapy against breast cancer. [ABSTRACT FROM AUTHOR]

Alpha mangostin, a natural xanthone derivative from mangosteen fruit pericarp, exhibits antiproliferative and apoptotic effects on different cancer cells by inhibiting cell cycle progression, inducing apoptosis, and modulating signaling pathways. However, this candidate is limited in medical treatment due to the poor water solubility. Nanoparticles have emerged as promising drug delivery systems to improve drug delivery efficiency but one of the problem of nanoparticles is the capability of endosomal escape. Therefore, pH-sensitive polymer nanosystems were utilized for targeted drug delivery, and enhanced efficacy by offering controlled release and endosomal escape capabilities. This study aimed to synthesize PEG- P(Asp-Hyd-Man) copolymer and create micelle for alpha mangostin delivery. The micelles were measured with particle size average of 80.2 ± 15 nm, and the PDI of 0.17. Additionally, the release behavior of alpha mangostin was examined in vitro that show pH-sensitive polymeric micelles rapidly release at pH 5.0 compared with the arterial pH 7.4. The findings of this study are significant in the development of an effective drug delivery system using alpha mangostin and other therapeutic agents. [ABSTRACT FROM AUTHOR]

Cellulose-based actuators hold great promise for diverse applications, including soft robotics, biomedicine, and electronics. Achieving reversible motion is crucial to design high performance bio-based actuators. In this study, we explore the impact of carboxymethylation and 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) oxidation on the reversible performance of cellulose-based pH-responsive actuators. Both methods introduce negatively charged groups onto the surface of cellulose fibers, enabling increased water uptake at high pH. However, comparative analyses revealed structural differences, guiding the design of reversible actuators. Carboxymethylated CNFs (CMCNFs) displayed enhanced water uptake and pH sensitivity, attributed to their less cohesive structure. Actuation and reversibility tests on bilayer films validated these findings. This research advances the understanding of cellulose functionalization for tailored actuation, contributing to the development of programmable materials for multiple applications. [ABSTRACT FROM AUTHOR]

BACKGROUND: This study aimed to improve the stability and utilization of sulforaphene (SFE) and to enhance the intestinal stability and pH‐sensitive release of SFE in the gastrointestinal tract. To achieve this objective, calcium chloride (CaCl2) was used as a crosslinking agent to fabricate novel SFE‐loaded gellan gum (GG)‐ε‐polylysine (ε‐PL) pH‐sensitive hydrogel microspheres by using the ionic crosslinking technique. RESULTS: The molecular docking results of GG, ε‐PL, and SFE were good and occurred in the natural state. The loading efficiency (LE) of all samples was above 70%. According to the structural characterization results, GG and ε‐PL successfully embedded SFE in a three‐dimensional network structure through electrostatic interaction. The swelling characteristics and in vitro release results revealed that the microspheres were pH‐sensitive, and SFE was mainly retained inside the hydrogel microsphere in the stomach, and subsequently released in the intestine. The result of cytotoxicity assay showed that the hydrogel microspheres were non‐toxic and had an inhibitory effect on human colon cancer Caco‐2 cells. CONCLUSION: Thus, the hydrogel microspheres could improve SFE stability and utilization and achieve the intestinal targeted delivery of SFE. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

In this study, G/CMC/HAP-based nanocomposite hydrogel is synthesized as a nanocarrier for the targeted delivery of 5-FU by double emulsion (W/O) method in order to improve absorption and enhance the drug's effectiveness in suppressing breast cancer cells (MCF-7). The stability and preservation of 5-FU are improved by the addition of HAP nanoparticles, which boosts the pH-sensitive and span 80 content in the nanocarrier. The formation of the G/CMC/HAP nanocomposite containing 5-FU is confirmed by molecular and crystal structure, surface morphology, and physicochemical properties analysis using FTIR, XRD, FESEM, DLS, and Zeta potential. Zeta potential and DLS analysis indicate good stability of nanocarriers and a favorable particle size distribution of nanocomposites, with a medium size of 218 nm, appropriate for pharmaceutical applications. In comparison to previous studies, the current study's drug loading and entrapment efficiencies have greatly risen. The MTT assay is employed to assess cytotoxicity levels, while the flow cytometry analysis is used to appraise apoptosis in MCF-7 cells. Finally, according to the study's findings, due to its biocompatibility and pH-responsiveness, the nanocarrier created utilizing the double emulsion approach is a very promising candidate for the controlled release of 5-FU for the therapy of breast cancer. [ABSTRACT FROM AUTHOR]

A novel hybrid of silica-gelatin modified by bovine serum albumin-folate was designed in the current study as a pH-sensitive drug carrier. The fluorouracil was loaded by entrapment efficiency of 70%. The nanocarrier was evaluated in terms of pH-sensitive release behavior in simulated acidic condition of cancer tissue (pH = 5.6), and the normal physiological condition of the body (pH = 7.4) for 96 h. In vitro, drug release from nanocarriers indicated a partial rapid release in the early times (34 and 21% after 12 h in acidic and neutral media), which was followed by a sustained and gradual release profile up to 65% in acidic medium, and 42% in natural medium after 96 h, confirming the pH-responsive behavior of the developed nanocarrier. The Higuchi model adequately described the release data. The results of kinetic model indicated that the release process is mainly controlled through diffusion mechanism. The toxicity study showed low toxicity of drug-free carriers against normal human dermal fibroblast cells (HDF) and human ovarian cancer cells (OVCAR-3). These outcomes support the proper function of the designed hybrid nanocarrier in targeted drug delivery. [ABSTRACT FROM AUTHOR]

Abstract Background Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. Methods DOX was conjugated to the polymer through a hydrazine linker by Schiff’s base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). Results The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. Conclusions These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response. Graphical Abstract

A pH‐sensitive protein fibre membrane was prepared using alizarin (ALI), curcumin (CUR), gelatin, zein and cinnamaldehyde as raw materials, by electrospinning technology. The membrane was developed to detect food deterioration and extend shelf life. It was observed that the addition of CUR significantly enhanced the antioxidant and barrier properties of the membrane. The fibre membrane was responsive to pH with minimal colour alteration in response to humidity (from 20% to 80% relative humidity) and demonstrated excellent reusability along with a low detection limit for ammonia gas. Moreover, it was capable of monitoring low concentrations of bacteria in the headspace. To assess the efficacy of the membrane, a freshness monitoring and preservation study was carried out on pork stored at 4°C for 5 days. The fibre membrane not only prolonged the shelf life of meat but also allowed real‐time monitoring of its freshness. The results highlight the potential application of the prepared nanofibres in the simultaneous monitoring and preservation of meat freshness. [ABSTRACT FROM AUTHOR]

Background: Designing and preparing a co-delivery system based on polymeric micelles have attracted in recent years. Co-delivery of anti-cancer agents within pH-sensitive polymeric micelles could provide superior advantages over the co-administration of free drugs, since it enables simultaneous delivery of drugs to reach an optimum synergistic dose right to the tumor. Methods: DOX was conjugated to the polymer through a hydrazine linker by Schiff's base reaction. Then, DTX was encapsulated into the core of the polymer to the resulting DOX-Hyd-PM/DTX micelle with optimum molar ratios of 1:1 and 1:5 (DOX/DTX). Results: The final formulations showed the desired particle size and increased release of DOX and DTX in acidic media (pH 5.5). The cytotoxicity assay of DOX-Hyd-PM/DTX indicated the highest synergistic effect on both 4T1 and TUBO cell lines over other formulations. Interestingly, in accordance with in vitro results, DOX-Hyd-PM/DTX revealed a promising anti-tumor activity in mice-bearing 4T1 breast cancer tumor with higher tumor accumulation of DOX and DTX after 24 h compared to free drugs combination. Conclusions: These findings point to the potential use of such smart nanodrug delivery systems in cancer treatment, where the synergistic effect of both drugs may be used to enhance therapeutic response. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Zeolitic imidazolate framework-8 (ZIF-8) is a promising material for drug delivery, but its poor stability limits its wide application. In this work, homogeneous dodecahedral ZIF-8 was prepared by the room-temperature solution stirring method, and to improve the stability of ZIF-8, ZIF-8@mSiO2 and DZIF-8 (ZIF-8 after calcination) @PMO composites with the core-shell structure were obtained using mesoporous silica (mSiO2) and periodic mesoporous organic silica (PMO) coatings. Folic acid-coupled chitosan (CS-FA) was modified on nanoparticles, and curcumin (CUR) was used as a model anti-tumor drug to obtain the drug delivery systems with targeting and pH stimulation response: ZIF-8@mSiO2@CUR@CS-FA and DZIF-8@PMO@CUR@CS-FA, which exhibited good dispersion and high drug loading capability. In addition, we used the MTT assay to assess the cytotoxicity of the drug-carrying systems and selected human cervical cancer cells (Hela) as model cells. The results of the in vitro experiments suggested that the final CUR-loaded drug delivery systems had significantly increased anticancer efficiency compared with the free drug CUR, which improved the therapeutic effect of the hydrophobic CUR on tumors. In conclusion, the pH-responsive nanocarriers provided potential for the targeted delivery of anticancer medication, resulting in a platform for drug-controlled release and cancer therapy. [ABSTRACT FROM AUTHOR]

Silica-based scaffolds are promising in Tissue Engineering by enabling personalized scaffolds, boosting exceptional bioactivity and osteogenic characteristics. Moreover, silica materials are highly tunable, allowing for controlled drug release to enhance tissue regeneration. In this study, we developed a 3D printable silica material with controlled mesoporosity, achieved through the sol-gel reaction of tetraethyl orthosilicate (TEOS) at mild temperatures with the addition of different calcium concentrations. The resultant silica inks exhibited high printability and shape fidelity, while maintaining bioactivity and biocompatibility. Notably, the increased mesopore size enhanced the incorporation and release of large molecules, using cytochrome C as a drug model. Due to the varying surface charge of silica depending on the pH, a pH-dependent control release was obtained between pH 2.5 and 7.5, with maximum release in acidic conditions. Therefore, silica with controlled mesoporosity could be 3D printed, acting as a pH stimuli responsive platform with therapeutic potential.

In this study, a novel quantum dot (QD)-labeled specific anti-prostate-specific membrane antigen (PSMA) aptamer sequence was conjugated to a pH-responsive niosomal particle platform for delivery of docetaxel (DTX) components. The target cells were overexpressed PSMA. This strategy can minimize the systemic toxicity prevalent in DTX. Synthesis of pH-responsive niosomes was achieved by using thin-film hydration. The conjugation of the aptamer A10 to the niosomal particle was done via a disulfide bond. Furthermore, CdSe/ZnS QDs were fabricated using a hot-injection process, then were functionalized with mercapto propanoic acid (MPA) ligands and attached to the 3’ terminal of aptamer via an Amide bind. Moreover, several characterization analyses including dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were performed. Additionally, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and apoptosis assays, as well as fluorescence microscopy, were used to assess the performance of the fabricated system. The data revealed a homogenous round-shaped population of niosomes with an average size of 200 nm and a negative surface charge was synthesized successfully. The FTIR and XRD evaluations confirmed the fabrication of both QDs and niosomes and the bioconjugation processes. The drug release happened in a controlled manner with a pH-sensitivity feature. The cellular uptake of aptamer-conjugated particles enhanced and consequently caused more cytotoxicity of prostate cancer cells with overexpression of PSMA. Furthermore, the QDs provided an ability to trace the treatment and its uptake via the targeted tissue. Overall, this study contributed to the development of a low-risk, highly specific platform for the delivery of both therapeutics and imaging agents.

Abstract Background Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. Results The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. Conclusions Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

Cell-free DNA (cfDNA) released from dead cells could be a player in some autoimmune disorders by activating Toll-like receptor 9 (TLR9) and inducing proinflammatory cytokines. Cationic nanoparticles (cNPs) address cfDNA clearance, yet challenges persist, including toxicity, low specificity and ineffectiveness against endocytosed cfDNA. This study introduced pH-sensitive cNPs, reducing off-target effects and binding cfDNA at inflammatory sites. This unique approach inhibits the TLR9 pathway, offering a novel strategy for inflammation modulation. Synthesized cNPs, with distinct cationic moieties, exhibit varied pKa values, enhancing cfDNA binding. Comprehensive studies elucidate the mechanism, demonstrating minimal extracellular binding, enhanced endosomal DNA binding, and optimal tumor necrosis factor-α suppression. In a traumatic brain injury mice model, pH-sensitive cNPs effectively suppress inflammatory cytokines, highlighting their potential in acute inflammation regulation. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, we synthesized pH-sensitive CHX@SBA-PDA nanoparticles and characterized their structure. These nanoparticles were then incorporated into Single Bond 2 commercial dentin adhesive. Subsequently, timely and long-term antibacterial evaluation, cytotoxicity evaluation and bonding properties were conducted. The results demonstrated the successful synthesis of CHX@SBAPDA nanoparticles. Moreover, CHX@SBA-PDA exhibited excellent pH sensitivity and maintained a high release rate of chlorhexidine (CHX) under cariogenic low pH conditions. At pH 5.0, the release rate could reach up to 71.1% after 24 h of incubation with CHX@SBA-PDA nanoparticles. Among the different adhesive formulations tested, the 2% wt adhesive displayed the strongest immediate and 30 days bacterial inhibition ability (p < 0.05). No significant difference was observed in immediate shear strength among the four groups (p > 0.05). After undergoing pH cycling, all functional adhesive groups exhibited higher shear strength compared to the control group (p < 0.05). Furthermore, there was no significant difference in cell proliferation activity between the experimental group and control group (p > 0.05). In conclusion, our functional dentin adhesive containing CHX@SBA-PDA nanoparticles demonstrated long-term antibacterial properties as well as improved bond strength characteristics, thus, offering a promising approach to enhance durability of bonded restorations. [ABSTRACT FROM AUTHOR]

AbstractA hybrid nanocarrier based on silica-alginate modified by gelatin-folic acid was designed as a pH-sensitive drug delivery system and investigated in the terms of in terms of the amount of doxorubicin loading and release behavior in two different mediums with pH 7.4 and 5.6. The loading content and entrapment efficiency were measured at about 21% and 67%, respectively. The results showed a rapid release of the doxorubicin from the unmodified carrier at initial times (first 24 h). While the use of gelatin-folate modification led to the improvement of the release behavior. Here, the amount of drug released from the silica-alginate carrier after 72 h in a neutral and acidic environment was measured as 82% and 73%, respectively. While using gelatin modification, the amount of released drug decreased to 71% and 63%. These results show that the prepared carrier is sensitive to pH. Furthermore, the cross-linking effect of the gelatin modifier layer on the release pattern was investigated and results indicated the improvement of the release pattern in both acidic and natural media. The findings of this research show the appropriate performance of carriers designed for drug delivery. [ABSTRACT FROM AUTHOR]

Summary: Recently, the assimilation of pH‐sensitive natural pigments into biopolymers has shown promising prospects for pH‐reactive based smart packaging material. Unlike synthetic pigments, which have potential safety problems due to migration, natural pigments have negligible toxicity levels both to humans and the environment and some even possess nutritional and pharmacological properties. To complement the advantages of natural pigments, natural biopolymers have proven to be ideal candidates for the development of smart packaging because of their biocompatibility, availability, biodegradability, stability, minimum toxicity and good film‐forming capability. Smart packaging gives consumers real‐time signals on the quality of packaged food via food deterioration indicators like pH alteration. This review will consider the recent progress in the development of pH‐responsive smart packaging based on natural pH‐sensitive pigments and natural biopolymers from 2013 to the present. It will further discuss the challenges and opportunities of colorimetric smart packaging. [ABSTRACT FROM AUTHOR]

Tripterygium wilfordii Hook F, a traditional medicine in China has bioactive but toxic triptolide (TP, a diterpenoid triepoxide) as its main active constituents. The applications of TP are hampered by its prominent toxicity and low solubility in water. In this study, a safe pH-sensitive material [methoxy polyethylene glycol (mPEG)- adipic dihydrazide (ADH)] was synthesized and loaded with TP to form pH-sensitive polymeric micelles, thereby improving the safety and solubility of TP, as well as providing a theoretical basis for the wide application of TP. The mPEG-ADH/TP micelles were characterized by a series of indicators [namely entrapment efficiency (EE), critical micellar concentration (CMC), electrokinetic potential, stability, polydispersed index (PDI), and particle size]. Also, we ascertained the in vitro release of TP from mPEG-ADH/TP micelles along with pharmacokinetic investigations in vivo. Besides, we evaluated the cytotoxicity of mPEG-ADH/TP micelles against A549 cells, HCT116 cells, and HaCat cells and further conducted in vivo toxicity studies in rats. The TP-loaded mPEG-ADH micelles had smaller sized particles (48.3 nm), excellent PDI (0.142), stable property and higher EE (89.87%). Importantly, the TP in the mPEG-ADH/TP micelles was almost completely released at acidic pH (pH 5.0), while the drug was released slowly and sparingly at physiological pH (pH 7.4). The results suggest the release of TP from mPEG-ADH/TP micelles was sensitive to pH, which could facilitate targeting of the drug into intra-cellularly low pH endosomes and lysosomes as well as enhance cytotoxicity in cancer tissues. Moreover, mPEG-ADH/TP micelles exhibited excellent proliferation inhibition on tumor cells. In addition, the liver injury of rats in the 1 mg/kg dose of mPEG-ADH/TP micelles group was significantly reduced by Hematoxylin–eosin (HE) staining. Taken together, mPEG-ADH/TP micelles could act as a promising alternative to enhance the efficacy of oncologic treatments. [ABSTRACT FROM AUTHOR]

In this study, we present a targeted and pH-sensitive niosomal (pHSN) formulation, incorporating quantum dot (QD)-labeled Trastuzumab (Trz) molecules for the specific delivery of Palbociclib (Pal) to cells overexpressing human epidermal growth factor receptor 2 (HER2). FTIR analyses confirmed the successful preparation of the pHSNs and their bioconjugation. The labeled Trz-conjugated Pal-pHSNs (Trz-Pal-pHSNs) exhibited a size of approximately 170 nm, displaying a spherical shape with a neutral surface charge of −1.2 mV. Pal encapsulation reached ∼86%, and the release pattern followed a two-phase pH-dependent mechanism. MTT assessments demonstrated enhanced apoptosis induction, particularly in HER2-positive cells, by Trz-Pal-pHSNs. Fluorescence imaging further validated the internalization of particles into cells. In conclusion, Trz-Pal-pHSNs emerge as a promising platform for personalized medicine in the treatment of HER2-positive breast cancer.

Abstract Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (β-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer.

Anthocyanin is an important flavonoid with antioxidant, anticancer, and anti-inflammatory properties. This research investigates the anthocyanin content of Cavendish banana inflorescence, a by-product often discarded as agricultural waste. The study employs two drying methods, namely oven-drying and freeze-drying, followed by accelerated solvent extraction using acidified water and methanol. Liquid chromatography-mass spectroscopy (LC-MS) results confirm banana inflorescence as a rich source of anthocyanins. According to LC-MS analysis, freeze-dried banana inflorescence extracted in methanol at 80 °C exhibits the highest anthocyanin content (130.01 mg/100 g). This sample also demonstrates superior characteristics, including a chroma value of 40.02 ± 0.01, a redness value of 38.09 ± 0.16, 18.46 ± 0.02 °Brix, a total phenolic content of 42.5 ± 1.00 mg/g, expressed as gallic acid equivalents, and a total antioxidant activity of 71.33 ± 0.08% when assessed with the DPPH method. Furthermore, the study identifies the predominant anthocyanin as cyanidin, along with the presence of other anthocyanins such as delphinidin (Dp), malvidin (Mv), petunidin (Pt), pelargonidin (Pg), and peonidin (Pn). Interestingly, the extracted anthocyanins demonstrate pH sensitivity, changing from red to brown as pH increases. These findings highlight the potential of utilizing Cavendish banana inflorescence for anthocyanin extraction, offering sustainable waste valorization methods with promising applications in biomimetics and bioinspiration fields.

Background: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. Methods: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box–Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. Results: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. Conclusions: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen.

The present work aimed to study the feasibility of Angelica sinensis polysaccharide (ASP) as an instinctive liver targeting drug delivery carrier for oridonin (ORI) in the treatment of hepatocellular carcinoma (HCC). ASP was reacted with deoxycholic acid (DOCA) via an esterification reaction to form an ASP-DOCA conjugate. ORI-loaded ASP-DOCA nanoparticles (ORI/ASP-DOCA NPs) were prepared by the thin-film water method, and their size was about 195 nm in aqueous solution. ORI/ASP-DOCA NPs had a drug loading capacity of up to 9.2%. The release of ORI in ORI/ASP-DOCA NPs was pH-dependent, resulting in rapid decomposition and accelerated drug release at acidic pH. ORI/ASP-DOCA NPs significantly enhanced the accumulation of ORI in liver tumors through ASGPR-mediated endocytosis. In vitro results showed that ORI/ASP-DOCA NPs increased cell uptake and apoptosis in HepG2 cells, and in vivo results showed that ORI/ASP-DOCA NPs caused effective tumor suppression in H22 tumor-bearing mice compared with free ORI. In short, ORI/ASP-DOCA NPs might be a simple, feasible, safe and effective ORI nano-drug delivery system that could be used for the targeted delivery and treatment of liver tumors. [ABSTRACT FROM AUTHOR]

The abuse of plastic food packaging has brought about severe white pollution issues around the world. Developing green and sustainable biomass packaging is an effective way to solve this problem. Hence, a chitosan/sodium alginate- based multilayer film is fabricated via a layer-by-layer (LBL) self-assembly method. With the help of superior interaction between the layers, the multilayer film possesses excellent mechanical properties (with a tensile strength of 50 MPa). Besides, the film displays outstanding water retention property (blocking moisture of 97.56%) and ultraviolet blocking property. Anthocyanin is introduced into the film to detect the food quality since it is one natural plant polyphenol that is sensitive to the pH changes ranging from 1 to 13 in food when spoilage occurs. It is noted that the film is also bacteriostatic which is desired for food packaging. This study describes a simple technique for the development of advanced multifunctional and fully biodegradable food packaging film and it is a sustainable alternative to plastic packaging. [ABSTRACT FROM AUTHOR]

Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (β-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

pH-sensitive fluorescent proteins have revolutionized the field of cellular imaging and physiology, offering insight into the dynamic pH changes that underlie fundamental cellular processes. This comprehensive review explores the diverse applications and recent advances in the use of pH-sensitive fluorescent proteins. These remarkable tools enable researchers to visualize and monitor pH variations within subcellular compartments, especially mitochondria, shedding light on organelle-specific pH regulation. They play pivotal roles in visualizing exocytosis and endocytosis events in synaptic transmission, monitoring cell death and apoptosis, and understanding drug effects and disease progression. Recent advancements have led to improved photostability, pH specificity, and subcellular targeting, enhancing their utility. Techniques for multiplexed imaging, three-dimensional visualization, and superresolution microscopy are expanding the horizon of pH-sensitive protein applications. The future holds promise for their integration into optogenetics and drug discovery. With their ever-evolving capabilities, pH-sensitive fluorescent proteins remain indispensable tools for unravelling cellular dynamics and driving breakthroughs in biological research. This review serves as a comprehensive resource for researchers seeking to harness the potential of pH-sensitive fluorescent proteins. [ABSTRACT FROM AUTHOR]

The current work focused on developing a pH-sensitive nanocarrier for sustained release of 5-fluorouracil (5FU) for potential cancer therapy applications. The magnetic carboxylated graphene oxide was functionalized with taurine (Fe3O4/CGO─Tau) and characterized by several techniques, including X-ray diffraction (XRD), fourier transform infrared (FTIR), vibrating-sample magnetometer (VSM), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FESEM)/energy dispersive X-ray (EDX). The initial 5FU concentration, initial solution pH, adsorbent quantity, temperature, and contact time were evaluated as factors affecting adsorption. The maximum drug loading capacity was discovered to be up to 35.4 mg/g (drug per adsorbent). The adsorption, release kinetics, and equilibrium data, as well as thermodynamic properties, were analyzed. The adsorption kinetics displayed a pseudo-second-order (PSO) model, and the experimental equilibrium data had a good fit with the Freundlich model. The negative values of thermodynamic parameters showed that the adsorption process is exothermic, spontaneous, and practicable. In-vitro release studies demonstrated pH-triggered 5FU release from the 5FU@Fe3O4/CGO─Tau nanocarrier, with 63.9% cumulative release at pH 5.6 versus 40.6% at pH 7.4 over 48 h, resulting in greater exposure of tumor cells to the drug molecules. The exponent n in the Peppas–Sahlin model was greater than 1, which demonstrated that the release of 5FU was controlled by a non-Fickian diffusion mechanism. [ABSTRACT FROM AUTHOR]

Ordered nanoporous silica such as MCM‐41 has silanol groups that can be chemically modified to effectively control the release of molecules. In this regard, MCM‐41 was functionalized with trithiocyanuric acid groups (TTCA‐MCM‐41) and offered as a novel carrier to the controlled release of metformin. TTCA‐MCM‐41 was synthesized and characterized. Thereafter, for 3 hours, saturated metformin solution was contacted with TTCA‐MCM‐41 to loading of drug. Finally, drug release profile was investigated in simulated body fluid (SBF) and phosphate buffers. The hexagonal symmetry of the TTCA‐MCM‐41 was confirmed by XRD patterns. The BET surface area, centred on N2 adsorption‐desorption, dropped from 846.5 m2/g for the MCM‐41 to 295.2 m2/g for the TTCA‐MCM‐41. With the use of FT‐IR spectra, the presence of TTCA groups in the silica system was established. The rope‐shaped morphology and the existence of S and N atoms on the MCM‐41 are visible in the SEM and EDX. The metformin release from TTCA‐MCM‐41 exhibits a pH‐based behaviour, and release rate was faster at higher pH compared to lower pH in phosphate buffers. In SBF, metformin displayed a steady release rate of around 0.2 mg min−1. The findings demonstrated that TTCA‐MCM‐41 is a promising candidate as a novel metformin carrier. [ABSTRACT FROM AUTHOR]

Drugs remain for a short time on mucus membranes, such as oral, ocular, or nasal mucus, which are washed with physiological fluids. One of the possibilities to overcome this obstacle is the application of solutions that, due to the physiological environment or stimulus, turn into more viscous gels. These gels often also have mucoadhesive properties and the drug is released from them for a longer period. Carbomer 940 (C940), polycarbophil (PCP), and chitosan (CH) are gel-forming excipients, and the consistency of their solutions changes due to the concentration of protons (pH); therefore, they are referred to as pH-sensitive gelling agents. The aim of this study was to prepare pH-sensitive solutions that form gels in the pH of the oral cavity. We prepared water solutions with various concentrations of gel-forming excipients and evaluated the appearance, pH of the solution, injectability of the solution, and pH of gelation. By determining the pH of gelation, suitable concentrations (w/w) of the used polymers were found, namely, 0.1% C940, 0.225% PCP, and 2.5% CH with medium molecular weight (CHM). The 0.1% C940 and 0.225% PCP solutions were injectable through the syringe with the smallest 0.5 mm needle diameter. The 2.5% CHM solution was not injectable even through the syringe with the largest 0.8 mm needle diameter. Solgels prepared at the determined concentrations were evaluated by a dissolution test in a pH 6.8 phosphate buffer using methylene blue (MB) as a model substance. After 60 min of dissolution, 77.04% ± 5.94%, 48.85% ± 5.74%, and 77.35% ± 4.98% of MB were released from samples with C940, PCP, and CHM, respectively. The dissolution of the C940 and CHM samples took place according to the Korsmeyer–Peppas kinetic model (R2 0.999 ± 0.001, 0.978 ± 0.003) and of the PCP samples took place according to the first-order model (R2 0.994 ± 0.001). The 0.225% PCP pH-sensitive gel showed the most advantageous properties in terms of injectability, pH gelation, and prolonged release of MB. [ABSTRACT FROM AUTHOR]

Nateglinide is an anti-diabetic agent that experiences modest first-pass metabolism and poor aqueous solubility. This paper explores the preparation, characterization, and evaluation of interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic)) acid as a potential carrier for the drug. Interpenetrating polymer network composite hydrogels of chitosan and poly(meth(methacrylic) acid incorporating nateglinide were prepared using N,Nꞌ-methylene bisacrylamide and glutaraldehyde as cross-linkers. The polymerization of chitosan, entrapment of the drug, and its interaction in prepared hydrogels were checked by FTIR spectroscopy, DSC, and powder XRD studies. The hydrogels were evaluated for their swelling behavior and in vitro drug release. The morphology of the hydrogels before and after dissolution was studied using SEM. The hydrogels showed a 93.29 ± 4.65% yield and 91.28 ± 2.22% drug loading. The hydrogels exhibited pH-sensitive swelling behavior. The in vitro release profile confirmed that the drug release depended on the swelling of hydrogels and showed a biphasic release pattern. Chitosan-poly(meth(methacrylic)) acid interpenetrating polymer network hydrogel, with its biodegradable nature and pH-sensitive release of nateglinide, is an attractive option to be further explored for targeted controlled drug delivery formulations for the drug. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX. [ABSTRACT FROM AUTHOR]

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.

Background: This study was done to achieve a new drug delivery system delivering two different chemotherapy molecules to the target tissue simultaneously. Significance: Co-delivery of chemotherapy medicines provides synergistic effects leading to lowering the dose of administered drugs and side effects. Methods: Doxorubicin (DOX) was introduced to water-soluble hyaluronic acid (Hyal) using 1-amino-3,3-diethoxy-propane (ADEP), as a pH-sensitive linker, to develop a new hydrophobic structure, i.e. Hyal-ADEP-DOX. The conjugates were grafted in three ratios (7.5%, 12.5%, and 20%) to Hyal and characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1HNMR). Cannabidiol (CBD) was physically loaded in the core of nano-micelles. Results: Prepared nano-micelles were analyzed for critical micelle concentration (CMC) particle size stability and drug release before and after loading the CBD. Hyal-ADEP-DOX-12.5 was the optimized ratio and had a mean diameter of 50 nm before loading the CBD and 120 nm after loading (observed by transmission electron microscopy). The release results showed that DOX releases slowly in physiological pH, and CBD has a burst release at acidic pH from Hyal-ADEP-DOX-12.5. These properties altogether make Hyal-ADEP-DOX nano-micelles, as a stimuli-sensitive nano-carrier, a potential candidate for hydrophobic anticancer agents’ co-delivery. Conclusion: The grafted DOX exhibited pH-sensitive release behavior, i.e. while 22.8% of the drug was released after 24 h at pH 5.5, and 5% was released after 24 h at pH 7.4. Hyal-ADEP-DOX due to its low CMC value, colloidal stability, slow drug release in physiological pH, and burst release in acidic pH Hyal-ADEP-DOX, is an excellent candidate as a carrier to co-deliver hydrophobic therapeutic agents to tumor tissues.

Breast cancer was first noted by the ancient Egyptians more than 3500 years ago. In India, the US, and China about 221757, 287750, and 429105 cases of breast cancer were reported in the year 2022. The conventional chemotherapeutic agents used in breast cancer not only kill the cancer cells but the healthy cells also. Hydrogels, composed of different polymers, targeted to deliver natural and synthetic cytotoxic drugs in the microenvironment of breast cancer are reviewed in this manuscript. This manuscript is focused on providing insight into smart hydrogel which improves the efficacy of chemotherapeutic agents used in the treatment of breast cancer. Smart hydrogels, in response to specific stimuli such as pH, temperature, light, etc., release cytotoxic drugs in breast cancer tissue and improve the retention time of the drug at the site of action. The site-specific delivery and retention of anticancer drugs help in reducing the adverse effects. Smart hydrogels have been gaining more attention for delivering cytotoxic drugs to tumor microenvironments in response to specific stimuli. This manuscript emphasizes the stimuli-sensitive hydrogels fabricated especially for breast cancer.

AbstractDoxorubicin (DOX), a commonly used anti-cancer drug, is limited by its cardiotoxicity and multidrug resistance (MDR) of tumor cells. Epigallocatechin gallate (EGCG), a natural antioxidant component, can effectively reduce the cardiotoxicity of DOX. Meanwhile, EGCG can inhibit the expression of P-glycoprotein (P-gp) and reverse the MDR of tumor cells. In this study, DOX is connected with low molecular weight polyethyleneimine (PEI) via hydrazone bond to get the pH-sensitive PEI-DOX, which is then combined with EGCG to prevent the cardiotoxicity of DOX and reverse the MDR of cancer cells. In addition, folic acid (FA) modified polyethylene glycol (PEG) (PEG-FA) is added to get the targeted system PEI-DOX/EGCG/FA. The MDR reversal and targeting ability of PEI-DOX/EGCG/FA is performed by cytotoxicity and in vivo anti-tumor activity on multidrug resistant MCF-7 cells (MCF-7/ADR). Additionally, we investigate the anti-drug resistant mechanism by Western Blot. The ability of EGCG to reduce DOX cardiotoxicity is confirmed by cardiotoxicity assay. In conclusion, PEI-DOX/EGCG/FA can inhibit the expression of P-gp and reverse the MDR in tumor cells. It also shows the ability of remove oxygen free radicals effectively to prevent the cardiotoxicity of DOX.

Nowadays, intelligent packaging has become very popular. It can quickly detect problems that arise during food production or circulation by monitoring the quality and safety of food. Anthocyanins have attracted widespread attention as a material for manufacturing smart food packaging, as they are sensitive to changes in pH, and small changes in pH can cause changes in the color of anthocyanins. The incorporation of anthocyanins often causes different changes in the properties of the films. The effects of anthocyanins on different properties of the films, including barrier, stability, mechanical properties, antioxidant, antibacterial and pH-sensitive were reviewed. We suggest that anthocyanins have the potential to extend the shelf life and monitor the food's freshness and quality in intelligent packaging. [ABSTRACT FROM AUTHOR]

The pH‐sensitive membranes have been extensively used in various fields. Through the incorporation of specific functional groups on pH‐sensitive molecules, diverse surface energies and degrees of wettability can be achieved at different pH values. In this study, we transformed pH‐sensitive copolymers into nanofibrillated membranes to increase their sensitivity to pH in terms of the contact angle formed by liquid droplets on their surface. Because N,N‐dimethylaminoethyl methacrylate (DMAEMA) contains an amino group, it is sensitive to acidic and alkaline environments. Moreover, to enhance the functionality, we selected styrene and methyl methacrylate (MMA) for random copolymerization with DMAEMA. We then used anodized aluminum oxide (AAO) templates to process the two copolymers into biomimetic fibrillated membranes. The contact angles between various‐pH aqueous droplets and different membranes were measured. Our results indicated that when the droplets were alkaline, the contact angle on the nanofibrillated membranes was large. When the pH of the droplets was decreased, the contact angle also decreased. In addition, the membranes were found to be reusable after being tested, washed, and dried. The surface free energy of nanofibrillated membranes with different molar feed ratios was also investigated in this study by using the model of Owens, Wendt, Rabel and Kaelble. [ABSTRACT FROM AUTHOR]

A myriad of pH-sensitive scaffolds has been reported in recent decades. Information on their behaviour in vitro under conditions that mimic the pH changes that occur during tissue regeneration is abundant. Differently, the in vivo demonstration of the advantages of pH-responsive systems in comparison with non-responders is more limited. The in vivo scenario is very complex and the intricate relationship between the host response, the overall pathological conditions of the patient, and the risk of colonization by microorganisms is very difficult to imitate in in vitro tests. This review aims to shed light on how the changes in pH between healthy and damaged states and also during the healing process have been exploited so far to develop polymer-based scaffolds that actively contribute in vivo to the healing process avoiding chronification. The main strategies so far tested to prepare pH-responsive scaffolds rely on (i) changes in ionization of natural polymers, ionizable monomers and clays, (ii) reversible cross-linkers, (iii) coatings, and (iv) production of CO 2 gas. These strategies are analysed in detail in this review with the description of relevant examples of their performance on specific animal models. The versatility of the techniques used to prepare biocompatible and environment-friendly pH-responsive scaffolds that have been implemented in the last decade may pave the way for a successful translation to the clinic. We report here on the most recent advances in pH-responsive polymer-based scaffolds that have been demonstrated in vivo to be suitable for wound and bone healing. pH is a critical variable in the tissue regeneration process, and small changes can speed up or completely stop the process. Although there is still a paucity of information on the performance in the complex in vivo environment, recently reported achievements using scaffolds endowed with pH-responsiveness through ionic natural polymers, ionizable monomers and clays, reversible cross-linkers, coatings, or formation of CO 2 ensure a promising future towards clinical translation. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Zinc oxide nanoparticles (ZnO NPs) have been known as a therapeutic agent and drug delivery system for treating various diseases, including infectious diseases and cancer. However, due to the low biocompatibility, short in vivo half-life, and potential toxicity, the previous studies on ZnO NPs were mainly focused on their in vitro applications. The effective and safe ZnO NP-based systems which can be used for in vivo drug delivery have been rarely reported. In this study, we developed a novel dual-responsive hybrid ZnO NP (ZnO/DPPG/PEG-pp-PE) consisting of the ZnO NPs, phospholipid (DPPG), and enzyme-sensitive amphiphilic polymer (PEG-pp-PE), which could respond to both tumoral matrix metalloproteinase 2 (MMP2) and intracellular acidic pH, for tumor-targeted drug delivery and multidrug resistant (MDR) cancer treatment. The dual-responsive ZnO/DPPG/PEG-pp-PE could easily load the model drug, doxorubicin (DOX), and showed excellent physicochemical properties, stability, and MMP2 and pH dual sensitivity. The ZnO/DPPG/PEG-pp-PE/DOX showed the MMP2-dependent cellular uptake, enhanced cell penetration, and improved anticancer activity in the MDR cancer cells and their spheroids. In the MDR tumor-bearing mice, the ZnO/DPPG/PEG-pp-PE/DOX improved the biocompatibility, tumor targetability, and anticancer activity of DOX and ZnO without significant toxicity compared to the free DOX, ZnO/DOX, and nonsensitive ZnO NPs. The data suggested that the dual-sensitive ZnO-based nanomedicine could be a promising delivery system for targeted drug delivery and therapy against the MDR cancer.

Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females. Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells (ECs), which represent the main technical difficulties for vaccine development, reside in the harsh, acidic human vaginal environment. Different from frequently employed viral vectors, two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses. Differing design concepts include the charge-reversal property (DRLS) to mimic a virus that uses any cells as factories, as well as the addition of a hyaluronic acid coating (HA/RLS) to directly target dendritic cells (DCs). With a suitable size and electrostatic neutrality, these two nanoparticles penetrate a mucus hydrogel with similar diffusivity. The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo. Therefore it induced more robust mucosal, cellular, and humoral immune responses. Moreover, the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA (naked), indicating timely protection against pathogens at the mucus layer. These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.

Abstract Nanosized drug delivery systems have rapidly emerged as a promising approach to tumor therapy, which still have many challenges in clinical application. In this study, doxorubicin-loaded O-carboxymethyl chitosan/perfluorohexane nanodroplets (O-CS-DOX NDs) were synthesized and functionally tested as an effective drug delivery system in vitro and in vivo. O-CS-DOX NDs with small size (159.6 nm) and good doxorubicin encapsuling ability showed pH- and ultrasound-dependent drug release profile and satisfying ultrasound imaging performance. With high biocompatibility and biosafety, these nanodroplets could accumulate in the tumor sites and exhibit high efficiency in inhibiting tumor growth with ultrasound irradiation. These stable, safe and smart O-CS-DOX NDs showed promising potential as a smart dual-responsive bomb for tumor ultrasonic imaging and treatment.