Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35 mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

Magnetic and pH-responsive magnetite/chitosan (core/shell) nanoparticles for dual-targeted methotrexate delivery in cancer therapy.

Methotrexate successful therapy encounters various challenges in chemotherapy, such as poor oral bioavailability, low specificity, side effects and the development of drug resistances. In this study, it is proposed a dual-targeted nanocarrier comprising magnetite/chitosan nanoparticles for an efficient Methotrexate delivery. The formation of the particles was confirmed through morphological analysis using electron microscopy and elemental mappings via energy dispersive X-ray spectroscopy. These nanoparticles exhibited a size of ≈ 270 nm, a zeta potential of ≈ 24 mV, and magnetic responsiveness, as demonstrated by hysteresis cycle analysis and visual observations under a magnetic field. In addition, these particles displayed high stability, as evidenced by size and surface electric charge measurements, during storage at both 4 ºC and 25 ºC for at least 30 days. Electrophoretic properties were examined in relation to pH and ionic strength, confirming these core/shell nanostructure. The nanoparticles demonstrated a pH-responsive drug release as observed by a sustained Methotrexate release over the next 90 h under pH ≈ 7.4, while complete release occurred within 3 h under acidic conditions (pH ≈ 5.5). In the biocompatibility assessment, the magnetite/chitosan particles showed excellent hemocompatibility ex vivo and no cytotoxic effects on normal MCF-10 A and cancer MCF-7 cells. Furthermore, the Methotrexate-loaded nanoparticles significantly enhanced the antitumor activity reducing the half-maximal inhibitory concentration by ≈ 2.7-fold less compared to the free chemotherapeutic.

Comparative Study of the Antibacterial Effects of S-Nitroso-N-acetylcysteine and Sodium Nitrite against Escherichia coli and Their Application in Beef Sausages.

This study investigated the antibacterial effects of S-nitroso-N-acetylcysteine (SNAC) and sodium nitrite (NaNO2) against Escherichia coli and their application in beef sausages. Both SNAC and NaNO2 demonstrated pH-responsive antibacterial activity, with SNAC showing greater efficacy than NaNO2 (p < 0.05) at the same pH (3, 5, and 7). The reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced in E. coli by SNAC were significantly higher than those induced by NaNO2 (p < 0.05), and both ROS and RNS values increased as the pH decreased. In addition, a lower pH led to more pores on the E. coli cell surface and increased membrane permeability, resulting in a more pronounced inhibitory effect. When applied to a beef sausage, SNAC-treated sausages had significantly lower total colony counts and carbonyl content compared to NaNO2-treated ones (p < 0.05). Consequently, SNAC shows great potential as a replacement for NaNO2 in meat products.

Association of Thermoresponsive Diblock Copolymer PDEGMA-b-PDIPAEMA in Aqueous Solutions: The Influence of Terminal Groups.

Aqueous solutions of a thermoresponsive diblock copolymer poly(di-[ethylene glycol] methyl ether methacrylate)-b-poly(2-[diisopropylamino] ethyl methacrylate) (PDEGMA-b-PDIPAEMA) were studied by static, dynamic and electrophoretic light scattering, small-angle X-ray scattering and differential scanning calorimetry. Thermoresponsive behavior of PDEGMA-b-PDIPAEMA was investigated at two pH values, pH = 2, at which the terminal carboxylic group of the PDEGMA chain and the PDIPAEMA block are protonated, and pH = 7, where the carboxyl terminal group is ionized while the PDIPAEMA block is partially deprotonated and more hydrophobic. Both at pH = 2 and 7, PDEGMA-b-PDIPAEMA copolymer underwent extensive association (the size of the aggregates was between 100 and 300 nm), indicating strong interchain interactions. While the measurements confirmed thermoresponsive behavior of PDEGMA-b-PDIPAEMA at pH = 7, no changes in the association with temperature were observed at pH 2 as the thermoresponsivity of PDEGMA was suppressed by hydrogen bonding between carboxylic groups and PDEGMA segments, as well as due to the increased hydrophilicity of the PDIPAEMA block. Fluorescence measurements with pyrene as a fluorescent probe showed that both at pH = 2 and pH = 7 the associates were able to solubilize hydrophobic substances.

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.

Preparation of Water-Soluble Polyion Complex (PIC) Micelles with pH-Responsive Carboxybetaine Block.

A dual zwitterionic diblock copolymer (M100C100) consisting of poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC, M) and poly(3-((2-(methacryloyloxy)ethyl) dimethylammonio) propionate) (PCBMA, C) is synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A double hydrophilic diblock copolymer (M100S100) consist of PMPC and anionic poly(3-sulfopropyl methacrylate potassium salt) (PMPS, S) is synthesized via RAFT. The degrees of polymerization of each block are 100. The charges of PMPC are neutralized intramolecularly. At neutral pH, the charges in PCBMA are also neutralized intramolecularly due to its carboxybetaine structure. Under acidic conditions, PCBMA exhibits polycation behavior as the pendant carboxy groups become protonated, forming cationic tertiary amine groups. PMPS shows permanent anionic nature independent of pH. Charge neutralized mixture of cationic M100C100 and anionic M100S100 in acidic aqueous solution forms water-soluble polyion complex (PIC) micelle owing to electrostatic attractive interactions. The core is composed of the cationic PCBMA and anionic PMPS blocks, with the PMPC blocks serving as shells that covered the core surface, forming spherical core-shell PIC micelles. Above pH 4 the pendant carboxy groups in PCBMA undergo deprotonation, transitioning to a zwitterionic state, thereby eliminating the cationic charge in PCBMA. Therefore, above pH 4 the PIC micelles are dissociated due to the disappearance of the charge interactions.

High adsorption capacities for dyes by a pH-responsive sodium alginate/sodium lignosulfonate/carboxylated chitosan/polyethyleneimine adsorbent.

Dyes are indispensable for the rapid development of society, but untreated dye wastewater can threaten human health. In this study, an adsorbent (SA/SL/CCS/PEI@MNPs) was synthesized by one-pot method using magnetic nanoparticles (MNPs), sodium alginate (SA), sodium lignosulfonate (SL), carboxylated chitosan (CCS) and polyethyleneimine (PEI). The adsorbent was mesoporous micrometer-sized particles with pore size of 34.92 nm, which was favorable for dynamic column experiments. SA/SL/CCS/PEI@MNPs possessed pH-responsive performance. Under acidic condition, the maximum adsorption capacities for anionic dyes (tartrazine, reactive black-5, indigo carmine) reached >550 mg/g. Under alkaline condition, those for cationic dyes (methylene blue, methyl violet, neutral red) exceeded 1900 mg/g. The function of the various modifiers was investigated. The results indicated that the incorporation of SL, CCS and PEI was able to provide plenty of sulfonate, carboxylate and amino/imine reactive groups so that adsorption capacities of dyes were improved. The adsorption mechanism was explored by FTIR and XPS. At the same time, the adsorption mechanism was more deeply analyzed using molecular dynamics simulations and radial distribution function. It was demonstrated that the dyes adsorption on the SA/SL/CCS/PEI@MNPs was mainly due to electrostatic attraction and π-π interaction. In addition, the adsorbent had good reusability, and the removal still reached over 90 % after five cycles. In conclusion, the adsorbent displayed a broad prospect for the adsorption of organic dyes.

The efficacy and safety of pH-responsive and photothermal-sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer.

A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.

Dual-Function Nanoscale Coordination Polymer Nanoparticles for Targeted Diagnosis and Therapeutic Delivery in Atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular events such as heart attacks and strokes. However, current medical practice lacks non-invasive, reliable approaches for both imaging atherosclerotic plaques and delivering therapeutic agents directly therein. Here, a biocompatible and biodegradable pH-responsive nanoscale coordination polymers (NCPs) based theranostic system is reported for managing atherosclerosis. NCPs are synthesized with a pH-responsive benzoic-imine (BI) linker and Gd3+. Simvastatin (ST), a statin not used for lowering blood cholesterol but known for its anti-inflammatory and antioxidant effects in mice, is chosen as the model drug. By incorporating ST into the hydrophobic domain of a lipid bilayer shell on NCPs surfaces, ST/NCP-PEG nanoparticles are created that are designed for dual purposes: they diagnose and treat atherosclerosis. When administered intravenously, they target atherosclerotic plaques, breaking down in the mild acidic microenvironment of the plaque to release ST, which reduces inflammation and oxidative stress, and Gd-complexes for MR imaging of the plaques. ST/NCP-PEG nanoparticles show efficacy in slowing the progression of atherosclerosis in live models and allow for simultaneous in vivo monitoring without observed toxicity in major organs. This positions ST/NCP-PEG nanoparticles as a promising strategy for the spontaneous diagnosis and treatment of atherosclerosis.

Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy.

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co3+ and Co2+ caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (·OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO2 nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination.

Gelatin-based carbon quantum dot-molecularly imprinted polymer: Safe photoluminescent core-shell nano-carrier for the pH-responsive anticancer drug delivery.

This study aims to synthesize a core-shell gelatin-based carbon quantum dot-molecularly imprinted polymer (MIP@g-CQD) via the precipitation free-radical polymerization process using methotrexate (MTX) as a model anticancer template. To investigate the efficiency of the prepared photoluminescent MIP@g-CQD as a pH-responsive nano-carrier, MTX was loaded into MIP@g-CQD by soaking in a drug solution and the release behavior of the loaded drug was evaluated in the necessary pH values (7.4, 5). The successful synthesis of materials was characterized using PL, TEM, FE-SEM, DLS, and FT-IR analyses. Interestingly, the created cavities in the core-shell nano-carriers can interact with the MTX molecules effectively, leading to an increase in the loading capacity. According to the obtained results from Langmuir adsorption isotherms, the imprinting factor was calculated (IF = 4.91). Also, the binding kinetics of MTX revealed the creation of particular recognition sites in the core-shell polymeric network. The MTX-loaded MIP@g-CQD displayed a low rate and limited release at the simulated physiological environment (pH 7.4, 37 °C), but it is increased at tumor tissue (pH 5, 41 °C) conditions, which can lead to long-term and sustained release of MTX in the desired target. This property of MIP@g-CQD could avoid the release of MTX in normal physiological conditions, decreasing the possible side effects of MTX drug. Owing to the existence of amide functional groups in the nano-carrier structure and its negatively charged nature, the MTT assay displayed desirable cytotoxicity against the breast cancer cell line (MCF-7) for the MTX-loaded nano-carrier. According to the obtained results, the prepared safe photoluminescent MIP@g-CQD with appropriate pH-responsivity has a high ability to be applied as an anticancer and bio-detection agent.

Highly functionalized pH-triggered supramolecular nanovalve for targeted cancer chemotherapy.

Chemotherapeutic drug delivery systems are commonly limited by their short half-lives, poor bioavailability, and unsuccessful targetability. Herein, pH-responsive hybrid NPs consist of benzimidazole-coated mesoporous silica nanoparticles (BZ-MSN) loaded with naturally occurring flavonoid quercetin (QUE-BZ-MSN). The NPs were further capped with beta-cyclodextrin (BCD) to obtain our desired BCD-QUE-BZMSN, with a zeta potential around 7.05 ± 2.37 mV and diameter about 115.2 ± 19.02 nm. The abundance of BZ onto the nanoparticles facilitates targeted quercetin chemotherapy against model lung and liver cancer cell lines. FTIR, EDX, and NMR analyses revealed evidence of possible surface functionalizations. Powder XRD analysis showed that our designed BCD-QUE-BZMSN formulation is amorphous in nature. The UV and SEM showed that our designed BCD-QUE-BZMSN has high drug entrapment efficiency and a nearly spherical morphology. In vitro, drug release assessments show controlled pH-dependent release profiles that could enhance the targeted chemotherapeutic response against mildly acidic regions in cancer cell lines. The obtained BCD-QUE-BZMSN nanovalve achieved significantly higher cytotoxic efficacy as compared to QUE alone, which was evaluated by in vitro cellular uptake against liver and lung cancer cell lines, and the cellular morphological ablation was further confirmed via inverted microscopy. The outcomes of the study imply that our designed BCD-QUE-BZMSN nanovalve is a potential carrier for cancer chemotherapeutics.

Preparation of bacterial cellulose/acrylic acid-based pH-responsive smart dressings by graft copolymerization method.

Conventional wound dressings used in trauma treatment have a single function and insufficient adaptability to the wound environment, making it difficult to meet the complex demands of the healing process. Stimuli-responsive hydrogels can respond specifically to the particular environment of the wound area and realize on-demand responsive release by loading active substances, which can effectively promote wound healing. In this paper, BC/PAA-pH responsive hydrogels (BPPRHs) were prepared by graft copolymerization of acrylic acid (AA) to the end of the molecular chain of bacterial cellulose (BC) network structure. Antibacterial pH-responsive 'smart' dressings were prepared by loading curcumin (Cur) onto the hydrogels. Surface morphology, chemical groups, crystallinity, rheological, and mechanical properties of BPPRHs were analyzed by different characterization methods. The drug release behavior under different physiological conditions and bacteriostatic properties of BPPRH-Cur dressings were also investigated. The results of structural characterization and performance studies show that the hydrogel has a three-dimensional mesh structure and can respond to wound pH in a 'smart' drug release capacity. The drug release behavior of the BPPRH-Cur dressings under different environmental conditions conformed to the logistic and Weibull kinetic models. BPPRH-Cur displayed good antimicrobial activity against common pathogens of wound infections such as E. coli, S. aureus, and P. aeruginosa by destroying the cell membrane and lysing the bacterial cells. This study lays the foundation for the development of new pharmaceutical dressings with positive health, economic and social benefits.

Programmed surface platform orchestrates anti-bacterial ability and time-sequential bone healing for implant-associated infection.

Implant-associated infection (IAI) has become an intractable challenge in clinic. The healing of IAI is a complex physiological process involving a series of spatiotemporal connected events. However, existing titanium-based implants in clinic suffer from poor antibacterial effect and single function. Herein, a versatile surface platform based on the presentation of sequential function is developed. Fabrication of titania nanotubes and poly-γ-glutamic acid (γ-PGA) achieves the efficient incorporation of silver ions (Ag+) and the pH-sensitive release in response to acidic bone infection microenvironment. The optimized PGA/Ag platform exhibits satisfactory biocompatibility and converts macrophages from pro-inflammatory M1 to pro-healing M2 phenotype during the subsequent healing stage, which creates a beneficial osteoimmune microenvironment and promotes angio/osteogenesis. Furthermore, the PGA/Ag platform mediates osteoblast/osteoclast coupling through inhibiting CCL3/CCR1 signaling. These biological effects synergistically improve osseointegration under bacterial infection in vivo, matching the healing process of IAI. Overall, the novel integrated PGA/Ag surface platform proposed in this study fulfills function cascades under pathological state and shows great potential in IAI therapy.

pH factors in chronic wound and pH-responsive polysaccharide-based hydrogel dressings.

Chronic wounds present a significant healthcare challenge marked by complexities such as persistent bleeding, inhibited cell proliferation, dysregulated inflammation, vulnerability to infection, and compromised tissue remodeling. Conventional wound dressings often prove inadequate in addressing the intricate requirements of chronic wound healing, leading to slow healing and heightened susceptibility to infections in patients with prolonged medical conditions. Bacterial biofilms in chronic wounds pose an additional challenge due to drug resistance. Advanced wound dressings have emerged as promising tools in expediting the healing process. Among these, pH-responsive polysaccharide-based hydrogels exhibit immense prospect by adapting their functions to dynamic wound conditions. Despite their potential, the current literature lacks a thorough review of these wound dressings. This review bridges this gap by meticulously examining factors related to chronic wounds, current strategies for healing, and the mechanisms and potential applications of pH-responsive hydrogel wound dressings as an emerging therapeutic solution. Special focus is given to their remarkable antibacterial properties and significant self-healing abilities. It further explores the pH-monitoring functions of these dressings, elucidating the associated pH indicators. This synthesis of knowledge aims to guide future research and development in the field of pH-responsive wound dressings, providing valuable insights into their potential applications in wound care.

An intelligent myofibrillar protein film for monitoring fish freshness by recognizing differences in anthocyanin (Lycium ruthenicum)-induced color change.

A novel smart film MP/BNC/ACN for real-time monitoring of fish freshness was developed using myofibrillar protein (MP) and bacterial nanocellulose (BNC) as film raw materials and anthocyanin (Lycium ruthenicum, ACN) as an indicator. Firstly, the film containing 1 % ACN (MP/BNC/ACN1) was found to have a moderate thickness (0.44 ± 0.01 mm) and superior mechanical properties (tensile strength (TS) = 8.53 ± 0.11 MPa; elongation at break (EB) = 24.85 ± 1.38 %) by determining the physical structure. The covalent, electrostatic, and hydrogen bonding interactions between anthocyanin and the film matrix were identified and confirmed by FT-IR spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscope (SEM) analysis. A comprehensive evaluation concluded that MP/BNC/ACN1 exhibited excellent trimethylamine (TMA) sensitivity (total color difference (ΔE), ΔETMA0-1000 = 4.47-31.05; limit of detection (LOD), LOD = 1.03) and UV stability (ΔE96h = 4.16 ± 0.13). The performance of the films in assessing fish freshness was evaluated, principal component analysis (PCA) and hierarchical cluster analysis (HCA) revealed that MP/BNC/ACN1 (ΔE2-10d = 16.84-32.05) could clearly distinguish between fresh (0-2 d), sub-fresh (4-6 d), and spoiled (8-10 d) stages of fish, which corresponded to the film colors of red, light red, and gray-black. In conclusion, this study addresses the limitation that intelligent films cannot visually discern real-time freshness during fish storage and provides a promising approach for real-time fish freshness monitoring.

Chitosan/cellulose nanocrystals/graphene oxide scaffolds as a potential pH-responsive wound dressing: Tuning physico-chemical, pro-regenerative and antimicrobial properties.

Chronic wounds (CWs) treatment still represents a demanding medical challenge. Several intrinsic physiological signals (i.e., pH) help to stimulate and support wound healing. CWs, in fact, are characterized by a predominantly alkaline pH of the exudate, which acidifies as the wound heals. Therefore, pH-responsive wound dressings hold great potential owing to their capability of tuning their functions according to the wound conditions. Herein, porous chitosan (CS)-based scaffolds loaded with cellulose nanocrystals (CNCs) and graphene oxide (GO) were successfully fabricated using a freeze-drying method. CNCs were extracted from bagasse pulps fibers through acid hydrolysis. GO was synthesised by Hummer's method. The scaffolds were then ionically cross-linked using the amino acid L-Arginine (Arg), as a bioactive agent, and tested as potential pH-responsive wound dressing. Notably, the effect of CNCs and GO singly and simultaneously loaded within the CS-Arg scaffolds was investigated. The modulation of CNCs and GO content within CS-Arg scaffolds facilitated the development of scaffolds with an optimal pH-dependent swelling ratio capability and extended degradation time. Furthermore, CS/CNC/GO-Arg scaffolds exhibited tuned biological features, in terms of antimicrobial activity, cellular proliferation/migration ability, and the expression of extracellular matrix specific markers (i.e., elastin and collagen I) related to wound healing in human dermal fibroblasts.

Ionized copolyesters with pH-responsive degradability: Accelerated degradation in specific environments.

The development of environmentally responsive biodegradable polymers is a promising solution for balancing the stability and degradability of biodegradable plastics. In this study, a commercial biodegradable polyester, poly(butylene adipate-co-butylene terephthalate) (PBAT), was used as the substrate and was synthetically modified with a small amount of anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) to obtain the ionized random poly(butylene adipate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBATS). The introduction of the sodium sulfonate ionic group enhanced the mechanical and heat-resistant properties of the material, while significantly improving the hydrophilicity and water absorption of the copolyesters of PBATSs and endowing them with special pH-responsive degradation properties. Compared with PBAT, PBATS copolyesters could accelerate degradation in acidic or alkaline buffer solutions and natural seawater, while degradation was inhibited in neutral buffer solutions at pH 7.2. Degradation experiments in simulated gastric, intestinal, and body fluids revealed that the copolyester showed specific and rapid degradation in acidic gastric fluids. This environmentally-responsive degradable material greatly expands the special applications of biodegradable polyesters in the fields of environmental remediation and medical applications.

Synthesis of Gelatin Methacryloyl Analogs and Their Use in the Fabrication of pH-Responsive Microspheres.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering. GelMA can be produced with different degrees of methacryloyl substitution; however, the synthesis of this polymer has not been tuned towards producing selectively modified materials for single-component pH-responsive hydrogels. In this work, we have explored two different synthetic routes targeting different gelatin functional groups (amine, hydroxyl, and/or carboxyl) to produce two GelMA analogs: gelatin A methacryloyl glycerylester (polymer A) and gelatin B methacrylamide (polymer B). Polymers A and B were used to fabricate pH-responsive hydrogel microspheres in a flow-focusing microfluidic device. At neutral pH, polymer A and B microspheres displayed an average diameter of ~40 µm. At pH 6, microspheres from polymer A showed a swelling ratio of 159.1 ± 11.5%, while at pH 10, a 288.6 ± 11.6% swelling ratio was recorded for polymer B particles.

Water-soluble biodegradable polyesters with pH and ionic responsivity.

The synthesis of novel water-soluble polymers with biodegradability is an effective way to mitigate their negative environmental impacts. In this study, semi-aromatic copolyester poly(butylene succinate-co-butylene terephthalate) (PBST) with exceptional biodegradability is used as the resin matrix. Anionic sodium 1-3-isophthalate-5-sulfonate (SIPA) is introduced as a fourth monomer to prepare random poly(butylene succinate-co-butylene terephthalate-co-butylene 5-sodiosulfoisophthalate) (PBSTS) copolyesters by melt copolymerization. The incorporation of ionic groups enhances the hydrophilicity and water absorption of the copolyesters, resulting in water-soluble materials that exhibit ionic and temperature responsivity. Furthermore, the ionized biodegradable copolyesters demonstrate distinct pH-dependent degradation, which is accelerated at pH = 5.5 and 8.5 but inhibited at pH = 7.2. Degradation assessments in simulated body fluids reveal that the PBSTS copolyesters exhibit significant degradation in gastric fluids at pH = 1.5 with minimal degradation in intestinal fluids at pH = 6.8 and in body fluids at pH = 7.0. This unique degradation performance highlights the potential of these materials for addressing the challenges associated with selective drug delivery and localized controlled release in the human body.