pH-responsive Drug Release Research Articles

Application of Box-Behnken design in the optimization and development of albendazole-loaded zein nanoparticles as a drug repurposing approach for colorectal cancer management

Colorectal cancer (CRC) is the second cancer worldwide representing a major global health challenge. Numerous effective anticancer drugs have been developed in the last decade, yet the problem remains due to their low therapeutic index and nonspecificity. A new anticancer therapeutic paradigm is based on repurposing and nanoformulating drugs. Albendazole (ALB), a popular anthelmintic agent, was recently repurposed against CRC cells. In this study zein, an amphiphilic protein, was used to formulate nanoparticles (NPs) loaded with ALB. Box-Behnken design was selected to optimize the loaded NPs, the concentrations of polyvinyl alcohol, acetic acid, and the weight of zein were the independent variables. The dependent variables were the particle size, polydispersity index, and zeta potential. The optimized formula displayed a size of 84.3 ± 0.41 nm, PDI 0.13 ± 0.012, and a zeta potential of 42.5 ± 2.35 mV. ALB was successfully encapsulated into zein NPs and the release study revealed a desirable pH-responsive drug release behavior, that was negligible discharge during the first 2 h at pH 1.2 and progressive in the simulated colon environment reaching 71.1 ± 0.34 % at 6 h and 92.4 ± 1.11 % at 24 h. The anticancer effect of the loaded NPs on the human HCT116 cells showed favorable effects at 1 μM concentrations with a significant decrease in the IC50 at days 2 and 3 upon loading albendazole into zein NPs. ZNPs proved to be prospective nanocarriers that could be used for the delivery of repurposed drugs in CRC treatment.

Mitoxantrone release from Fmoc-protected amino acids coated magnetic carbon nanotubes: Computational and experimental study for cancer treatment

Nanoparticles have a high potential for use as drug carrier systems in cancer treatment to reduce severe side effects, as in the treatment of many other diseases. Due to their unique properties, carbon-based nanoparticles such as carbon nanotubes (CNTs) are among the most frequently used nanoparticles in drug carrier systems. In this study, magnetic single-walled CNTs (mCNTs) were synthesized, characterized, coated and their ability to carry the anticancer drug mitoxantrone (MTO) was investigated using computational and experimental methods. First, the mCNT coating capabilities of Fmoc-protected amino acids, Fmoc-Cys(trt)-OH and Fmoc-Trp-OH were demonstrated by Raman spectroscopy, thermogravimetric analysis, and X-ray photoelectron spectroscopy. Then, full-atom molecular dynamics simulations of MTO-CNT complexes in explicit water were used to understand Fmoc-amino acid and MTO loading experiments at the molecular level. Binding free energies calculated by the Molecular Mechanics/Poisson-Boltzmann Surface Area method suggested MTO-CNT complex stability even at elevated temperatures up to 350 K that can be achieved due to external magnetic stimuli. Drug loading at pH 9 and releases at physiological (pH 7.4) and lysosomal pH (pH 5.5) were carried out for uncoated and coated mCNTs. The drug release and characterization results showed that coated mCNTs have pH-responsive drug release, enhanced dispersibility, and superparamagnetic properties so they promise to be beneficial for MTO delivery in cancer treatment. Cell viability results demonstrated that the mCNT-Fmoc-Cys samples had higher cell viability compared to the mCNT and mCNT-Fmoc-Trp groups.

Cetuximab functionalized chitosan/hyaluronic acid-based nanoparticles loaded with cabazitaxel enhances anti-tumor efficacy in DMBA-induced breast cancer model in rats through spatial targeting

The article discusses the ionic gelation of cationic chitosan (CS) with anionic hyaluronic acid (HA) sodium salt to form nanoparticles in the range of 125 nm. The particles were further functionalized with cetuximab to endow it with the ability to spatially target the tumor over-expressing EGFR. Solid-state characterization of the particles using XRD, FTIR, and DSC revealed the formation of stable nanoparticles with Cabazitaxel loaded in the amorphous nanostructure. XPS study used to assess the surface characteristics indicated that the cetuximab was successfully anchored on the surface of the particle. The prepared CS-HA-Cmab-NP elicited a pH-responsive drug release behavior due to the presence of CS in the matrix. In vitro performance of the nanoparticles was evaluated on MDA-MB-231 breast cancer cell lines showed overall increase in efficacy. In vivo pharmacokinetic and anti-tumor effect evaluated in female Sprague Dawley rats indicated that the Cmab-conjugated nanoparticles improved half-life of cabazitaxel and tumor reduction capability with higher survival rate and lower reduction in body weight. The results indicate that CS/HA nanoparticles anchored with cetuximab show enhanced efficacy in reducing the breast cancer tumor in DMBA-induced breast tumor model through spatial targeting, consequently reducing the systemic toxicity.

Hyaluronic acid/chitosan microcapsules capped with hollow CuS nanoparticles for NIR/pH dual-responsive drug release

Hollow natural polysaccharide microcapsules have broad applications in drug delivery field due to their excellent biocompatibility and drug loading efficiency. In this paper, pH/near-infrared (NIR) dual-responsive microcapsules composed of hyaluronic acid (HA), chitosan (CS) and hollow CuS (HA/CS/HA@CuS) had been fabricated via a layer-by-layer (LbL) approach. The negative charge, rough surface and hollow structure of microcapsules are very favorable for loading positively charged DOX. As a result, hollow microcapsules display a high drug loading efficiency of 91.15 %. The variation in the degree of amino ionization at different pH values leads to the changes in the electrostatic force between CS/HA multilayers, resulting in the structural change in microcapsules. Therefore, microcapsules exhibit significant pH-responsive drug release properties. In addition, hollow CuS nanoparticles with excellent photothermal conversion ability are capped on the multilayer surface, enabling microcapsules to exhibit excellent NIR-responsive drug delivery properties. Overall, hyaluronic acid/chitosan-based hollow microcapsules with notable pH/NIR dual-responsiveness have been prepared, which can be used as a potential drug carrier for controlled drug delivery and photothermal chemical combination therapy.

Antimicrobial Peptide Hydrogel with pH-Responsive and Controllable Drug Release Properties for the Efficient Treatment of Helicobacter pylori Infection.

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

Injectable Salecan/hyaluronic acid-based hydrogels with antibacterial, rapid self-healing, pH-responsive and controllable drug release capability for infected wound repair

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli, respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field.

Nanosheet-assembled porous-wall hollow hydroxyapatite microspheres prepared by a template-free hydrothermal method for pH-responsive drug release

Template residues during the preparation of hydroxyapatite (HA) microspheres with hollow structures limit their biological applications to some extent. In this study, the nanosheet-assembled porous-wall hollow HA microspheres were successfully synthesized by a template-free hydrothermal method. SEM and TEM observations revealed that the prepared hollow HA microspheres were about 3–7 μm in diameter and were composed of an interior cavity and a porous shell assembled by nanosheets (consisting of radial nanorods arranged side-by-side). A possible mechanism for the formation of the hollow HA microspheres was proposed based on the time-gradient experiments. Furthermore, the hollow HA microspheres exhibited excellent vancomycin loading capacity (101.3 mg/g) and pH-responsive release properties. This study provides new inspiration for the design and various applications of hollow materials.

Magnetically actuated cisplatin-loaded nanoparticle collectives enhance drug penetration for potentiated ovarian cancer chemotherapy

Chemotherapy is the main clinical treatment for ovarian cancer, but still faces challenges of low drug targeting efficiency and insufficient drug permeability. Drug-loaded nanoparticle collectives, which are actuated by magnetic field, could be targeted to a designated location and achieve targeted drug delivery. In this work, we report a strategy that utilizes magnetic mesoporous silica nanoparticles loaded with cis-diaminodichloroplatinum (Fe3O4@SiO2-CDDP) for targeted delivery of chemotherapeutic drugs and enhances penetration into deep tumors. The Fe3O4@SiO2-CDDP collectives actively moved to the target tumor site, and this movement was regulated by a magnetic actuation system. Under the action of a torque-force hybrid magnetic field (TFMF), Fe3O4@SiO2-CDDP could further penetrate into the interior of tumors and achieve pH-responsive drug release in the tumor environment. The feasibility of this strategy was verified in three-dimensional cell spheres in vitro and in a tumor-bearing mouse model in vivo. This magnetically actuated nanoparticle collectives enhanced drug penetration strategy provides a new paradigm for targeted drug delivery and potentiated tumor therapy.

Interfacially Self-Assembled Mutifunctional Protein Thin Films for Accelerated Wound Healing.

The design of mutifunctional protein films for large-area spatially ordered arrays of functional components holds great promise in the field of biomedical applications. Herein, interfacial electrostatic self-assembly was employed to construct a large-scale protein thin film by inducing electrostatic interactions between three bovine serum albumin (BSA)-coated nanoclusters and cetyltrimethylammonium bromide (CTAB), leading to their spontaneous organization and uniform distribution at the oil-water interface. This protein film demonstrated excellent multienzyme functions, high antibacterial activity, and pH-responsive drug release capability. Therefore, it can accelerate the wound closure process through a synergistic effect that includes reducing local blood glucose levels, regulating cellular oxidative stress, eradicating bacteria, and promoting cell proliferation.

Illuminating the fight against breast cancer: Preparation and visualized photothermal therapy of hyaluronic acid coated ZIF-8 loading with indocyanine green and cryptotanshinone for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

Tunicate cellulose nanocrystal reinforced multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing

Hydrogels as skin wound dressings have been extensively studied owing to their good flexibility and biocompatibility. Nevertheless, the mechanical performance, adhesive capability, antifouling and antibacterial properties of conventional hydrogels are still unsatisfactory, which hinder the application of hydrogel for cutaneous healing. Here, we developed a novel biocompatible multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing, where naturally rigid polymers including quaternized chitosan (QCS) and Tunicate cellulose nanocrystals (TCNCs) are used as bioactive cross-linkers and reinforcers to endow the hydrogel with excellent mechanical and antibacterial property, and the synergistic contributions from the poly(acrylic acid/methacrylate anhydride dopamine/sulfobetaine methacrylate) (poly(AA/DMA/SBMA)) chains and QCS endow the hydrogel with excellent adhesive property, antioxidant, antifouling and pH-responsive sustained drug release capabilities. The optimized hydrogel exhibited high tensile strength (77.69 KPa), large tensile strain (889.9 %), large toughness (307.51KJ.m−3), high adhesive strength (35.57 KPa) and ideal compressive property. The in vivo infected full-thickness skin model demonstrated that the hydrogel with vanvomycin sustained release ability efficiently improved the granulation tissue formation, facilitating collagen deposition and reducing inflammatory expression, thus effectively accelerating wound healing. This superiorly skin-adhesive antibacterial biocompatible hydrogel appears to be a promising candidate for wound therapy.

Dynamic Covalent Boronic-Acid-Functionalized Alginate/PVA Hydrogels for pH and Shear-Responsive Drug Delivery.

Herein, we investigated hydrogels composed of boronic-acid-functionalized alginate and blended with polyvinyl alcohol (PVA) of different molecular weights to control the release of metoclopramide hydrochloride as a function of pH and shear stress. The functionalization of alginate introduced dynamic covalent bonding and pH-responsive properties that can modulate network connectivity. The study investigated the viscoelastic properties of the hydrogels, their drug release profiles, and their responsiveness to changes in pH and shear forces. The results showed that a higher PVA molecular weight and alkaline pH conditions increased hydrogel viscosity and stiffness due to a more stable and interconnected network structure than acidic pH. Metoclopramide release revealed that the hydrogels exhibited pH-responsive drug release behavior. The drug was more readily released under acidic conditions due to the instability of sp2-hybridized boronate ester bonds. The influence of shear forces on the release of metoclopramide was also investigated at shear rates of 1, 10, and 100 s-1, revealing their effect on matrix stiffening. Research shows that AlgBA/PVA hydrogels have unique properties, such as dynamic covalent bonding, that make them sensitive to external mechanical forces. This sensitivity makes them ideal for applications where physiological conditions trigger drug release.

Dual-Functionalized Mesoporous Silica Nanoparticles for Celecoxib Delivery: Amine Grafting and Imidazolyl PEI Gatekeepers for Enhanced Loading and Controlled Release with Reduced Toxicity.

The development of targeted drug delivery systems has been a pivotal area in nanomedicine, addressing challenges like low drug loading capacity, uncontrolled release, and systemic toxicity. This study aims to develop and evaluate dual-functionalized mesoporous silica nanoparticles (MSN) for targeted delivery of celecoxib, enhancing drug loading, achieving controlled release, and reducing systemic toxicity through amine grafting and imidazolyl polyethyleneimine (PEI) gatekeepers. MSN were synthesized using the sol-gel method and functionalized with (3-aminopropyl) triethoxysilane (APTES) to create amine-grafted MSN (MSN-NH2). Celecoxib was loaded into MSN-NH2, followed by conjugation of imidazole-functionalized PEI (IP) gatekeepers synthesized via carbodiimide coupling. Characterization was conducted using Fourier-transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H-NMR). Drug loading capacity, entrapment efficiency, and in vitro drug release at pH 5.5 and 7.4 were evaluated. Cytotoxicity was assessed using the MTT assay on RAW 264.7 macrophages. The synthesized IP was confirmed by FTIR and 1H-NMR. Amine-grafted MSN demonstrated a celecoxib loading capacity of 12.91 ± 2.02%, 2.1 times higher than non-functionalized MSN. In vitro release studies showed pH-responsive behavior with significantly higher celecoxib release from MSN-NH2-celecoxib-IP at pH 5.5 compared to pH 7.4, achieving a 33% increase in release rate within 2 h. Cytotoxicity tests indicated significantly higher cell viability for IP-treated cells compared to PEI-treated cells, confirming reduced toxicity. The dual-functionalization of MSN with amine grafting and imidazolyl PEI gatekeepers enhances celecoxib loading and provides controlled pH-responsive drug release while reducing systemic toxicity. These findings highlight the potential of this advanced drug delivery system for targeted anti-inflammatory and anticancer therapies.

An anti-senescence hydrogel with pH-responsive drug release for mitigating intervertebral disc degeneration and low back pain

Oxidative stress and aging lead to progressive senescence of nucleus pulposus (NP) cells, resulting in intervertebral disc (IVD) degeneration (IVDD). In some cases, degenerative IVD can further cause low back pain (LBP). Several studies have confirmed that delaying and rejuvenating the senescence of NP cells can attenuate IVDD. However, the relatively closed tissue structure of IVDs presents challenges for the local application of anti-senescence drugs. Here, we prepared an anti-senescence hydrogel by conjugating phenylboronic acid-modified gelatin methacryloyl (GP) with quercetin to alleviate IVDD by removing senescent NP cells. The hydrogel exhibited injectability, biodegradability, prominent biocompatibility and responsive release of quercetin under pathological conditions. In vitro experiments demonstrated that the hydrogel could reduce the expression of senescence markers and restore the metabolic balance in senescent NP cells. In vivo studies validated that a single injection of the hydrogel in situ could maintain IVD tissue structure and alleviate sensitivity to noxious mechanical force in the rat models, indicating a potential therapeutic approach for ameliorating IVDD and LBP. This approach helps prevent potential systemic toxicity associated with systemic administration and reduces the morbidity resulting from repeated injections of free drugs into the IVD, providing a new strategy for IVDD treatment.

PH-responsive berberine release from metal-organic framework based nanocarriers by regulating oxidative stress for targeted therapy of oral squamous cell carcinoma

Excessive generation of reactive oxygen species (ROS) induces cellular oxidative stress damage, resulting in mitochondrial dysfunction and subsequent promotion of apoptosis. Induction of oxidative stress damage through chemo-dynamic therapy within the tumor microenvironment (TME) represents a promising therapeutic strategy for cancer treatment. Herein, folic acid-polyethylene glycol (FA-PEG)-modified MIL-101 NPs loaded with berberine (BER) were constructed to develop a nanoplatform based on the modulation of oxidative stress for the treatment of Oral squamous cell carcinoma (OSCC). Comprehensive characterizations based on TEM, DLS, XRD, FTIR, TGA and UV–vis spectroscopy confirmed the successful synthesis of MIL-101/PEG-FA with uniform size, high drug loading efficiency (32.59 %) and superior pH-responsive drug release (Ber release of 24.44 % and 70.22 % within 96h at pH 7.4 and 5.0, respectively). Cellular experiments revealed that MIL-101/PEG-FA achieved the pH-responsiveness release of the BER in the TME, thereby improving the bioavailability of BER. Moreover, Fe3+ in MIL-101(Fe) showed strong ability to consume GSH and provide a continuous supply of H2O2, which decreased SOD activity, and contributed to the generation of MDA, thereby increasing the production of toxic ROS in CAL27 cells. Meanwhile, MIL-101@BER/PEG-FA up-regulated inflammatory cytokine levels (TNF-α and IL-1β), promoted inflammatory response in TME, induced CAL27 cells apoptosis by regulating the LKB1/AMPK pathway. Finally, MIL-101@BER/PEG-FA showed good efficiency against OSCC in vivo. Consequently, MIL-101/PEG-FA can be applied as a nanocarrier platform for the treatment of OSCC.

BBB-penetrating magnetoelectric nanoparticles with sustainable Gel formulation for enhanced chemotherapy and reduced postoperative glioma recurrence

Overcoming blood–brain barrier (BBB), reducing drug resistance and inhibiting postoperative recurrence are the huge challenges of glioma treatment. Herein, a magnetoelectric nanoparticle, applying CoFe2O4 as magnetic core, BaTiO3 as piezoelectric shell and polyethylene glycol-connected I6P8 peptide as surface coating (CBPI), was used for glioma-targeted treatment. This nanoparticle could down-regulate tight junction proteins of BBB via magnetoelectric effect, synergized with I6P8 peptide, to achieve the enhanced BBB permeability and glioma targeting. Under magnetic field activation, this nanoparticle, after doxorubicin loading to formulate CBPID, could accomplish magnetoelectricity and pH-responsive drug release, and generate mild reactive oxygen species to sensitize the chemotherapy through c-Jun N-terminal kinase phosphorylation pathway. Importantly, CBPID facilitated intraoperative cavity administration with magnetic immobilization after easy doping to Surgiflo filler, benefiting the repeated magnetoelectric-activated therapy to inhibit glioma postoperative recurrence. Moreover, CBPID could be mostly excreted through feces after intravenous injection, which did not cause obvious blood and organ abnormalities and even improved the behavioral abnormalities caused by glioma.

Preparation and design of intelligent multi-response PTMC/PVP composite nanofibrous dressing to promote wound closure and its applications in diabetic wounds

The healing process of diabetic wounds is characterized by a slow and arduous progression, making it challenging to achieve wound closure and complete healing through self-contraction, as observed in normal wounds. In this study, an intelligent multi-responsive composite of polytrimethylene carbonate (PTMC)/polyvinylpyrrolidone (PVP) nanofibrous dressing (C-PPZS) loaded with simvastatin-loaded ZIF-8 nanoparticles (ZIF-8@SIM NPs) was fabricated via electrospinning technology. The dressing exhibited liquid-triggered and temperature-controlled shrinkage characteristics, as well as pH-responsive drug release properties. When subjected to a temperature of 37 ℃ for 60 min, the area shrinkage rate of PPZS in PBS was determined to be 78.36 ± 1.14 %, and C-PPZS also reduced the area of isolated mouse skin defects to 38.01 ± 2.33 % of its original size. Furthermore, in vitro studies demonstrated that C-PPZS exhibited favorable biocompatibility and proangiogenic properties, along with significant inhibitory effects against S. aureus and E. coli. In vivo experiments conducted on diabetic mice revealed that C-PPZS facilitated wound closure and healing, attenuated scar formation, stimulated collagen fiber deposition, and promoted vascular regeneration. In conclusion, C-PPZS has great potential as an advanced dressing for the treatment of chronic wounds.

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

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

A multifunctional nanoplatform for chemotherapy and nanocatalytic synergistic cancer therapy achieved by amplified lipid peroxidation

Traditional cancer chemotherapy suffers from low efficacy and severe side effects, limiting its use as a first-line treatment. To address this issue, we investigated a novel way to induce lipid peroxidation (LPO), which plays an essential role in ferroptosis and may be useful against cancer cells and tumors. In this study, a pH-responsive synergistic cancer therapy nanoplatform was prepared using CaCO3 co-loaded with oleanolic acid (OA) and lipoxygenase (LOX), resulting in the formation OLCaP NP. This nanoplatform exhibited good drug release properties in an acidic tumor environment owing to the presence of CaCO3. As a result of acidic stimulation at tumor sites, the OLCaP NP released OA and LOX. OA, a chemotherapeutic drug with anticancer activity, is already known to promote the apoptosis of cancer cells, and LOX is a natural enzyme that catalyzes the oxidation of polyunsaturated fatty acids, leading to the accumulation of lipid peroxides and promoting the apoptosis of cancer cells. More importantly, OA upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4), which promoted enzyme-mediated LPO. Based on our combined chemotherapy and nanocatalytic therapy, the OLCaP NP not only had remarkable antitumor ability but also upregulated ACSL4 expression, allowing further amplification of LPO to inhibit tumor growth. These findings demonstrate the potential of this nanoplatform to enhance the therapeutic efficacy against tumors by inducing oxidative stress and disrupting lipid metabolism, highlighting its clinical potential for improved cancer treatment. Statement of significanceThis study presents a novel nanoplatform that combines oleanolic acid (OA), a chemotherapeutic drug, and lipoxygenase (LOX), which oxidizes polyunsaturated fatty acids to trigger apoptosis, for targeted cancer therapy. Unlike traditional treatments, our nanoplatform exhibits pH-responsive drug release, specifically in acidic tumor environments. This innovation enhances the therapeutic effects of OA and LOX, upregulating acyl-CoA synthetase long-chain family member 4 expression and amplifying lipid peroxidation to promote tumor cell apoptosis. Our findings significantly advance the existing literature by demonstrating a synergistic approach that combines chemotherapy and nanocatalytic therapy. The scientific impact of this work lies in its potential to improve cancer treatment efficacy and specificity, offering a promising strategy for clinical applications and future research in cancer therapy.

The Role of Nanoparticle Morphology on Enhancing Delivery of Budesonide for Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that affects the gastrointestinal tract. The major hurdles impeding IBD treatment are the low targeting efficiency and short retention time of drugs in IBD sites. Nanoparticles with specific shapes have demonstrated the ability to improve mucus retention and cellular uptake. Herein, mesoporous silica nanoparticles (MSNs) with various morphologies were used to deliver budesonide (BUD) for the treatment of IBD. The therapeutic efficacy is strongly dependent on their shapes. The system comprises different shapes of MSNs as carriers for budesonide (BUD), along with Eudragit S100 as the enteric release shell. The encapsulation of Eudragit S100 not only improved the stability of MSNs-BUD in the gastrointestinal tract but also conferred pH-responsive drug release properties. Then, MSNs efficiently deliver BUD to the colon site, and the special shape of MSNs plays a critical role in enhancing their permeability and retention in the mucus layer. Among them, dendritic MSNs (MSND) effectively reduced myeloperoxidase (MPO) activity and levels of inflammatory cytokines in the colon due to long retention time and rapid release in IBD sites, thereby enhancing the therapeutic efficacy against colitis. Given the special shapes of MSNs and pH-responsivity of Eudragit S100, BUD loaded in the voids of MSND (E@MSNs-BUD) could penetrate the mucous layer and be accurately delivered to the colon with minor side effects. This system is expected to complement current treatment strategies for the IBD.