Drug Release Capacity Research Articles

Hydrogel coating based on dopamine-modified hyaluronic acid and gelatin with spatiotemporal drug release capacity for quick endothelialization and long-term anticoagulation

Due to the vital roles of vascular intima in preventing thrombus generation and maintaining vascular patency, methods to promote quick endothelialization on vascular grafts have drawn much attention. In this study, we novelly applied a double-layered hydrogel coating with spatiotemporal drug release capacity on a polycaprolactone (PCL) fibrous scaffold. The composite coating consisted of an inner dopamine-modified hyaluronic acid (HA) hydrogel and an outer gelatin hydrogel, which were generated via different crosslinking methods. Especially, heparin and chondroitin sulfate were introduced to the HA and gelatin hydrogels during the processing, thus endowing the vascular scaffold spatiotemporal drug release behavior. The composite coating developed surface hydrophilicity and mechanical properties of the PCL scaffold meanwhile stimulating the proliferation and angiogenesis behaviors of endothelial cells. Long-term anticoagulation property of the modified scaffold was also demonstrated in vitro. This investigation provides a universal strategy for quick endothelialization and long-term anticoagulation promotion of vascular grafts, which may be potentially used in treating cardiovascular diseases.

Highlights on Drug and Ion Release and Recharge Capacity of Antimicrobial Removable Prostheses.

This article aimed to review the ion and drug release, recharge abilities, and antimicrobial properties of drug/ion-releasing removable prostheses, and to assess their capability in preventing and inhibiting denture stomatitis as well preventing caries and reversing carious lesions. Data was collected from published scientific papers listed in PubMed database from January 1975 to December 2021. English full-text articles, involving clinical or in vitro studies, focusing on removable prostheses and are concerned with drug/ion release and rechargeability as a way to prevent or inhibit denture stomatitis or dental caries were included. The relevant articles reported that ion- or drug-modified polymethylmethacrylate acts as a reservoir for these ions and drugs and is capable of releasing significant amounts with sustained release effect. Recharging of modified resin resulted in greater sustainability of ion and drug release, thus improving the long-term effects of protection against demineralization and reducing the adhesion of Streptococcus mutans and Candida albicans. Modifications of removable prostheses with rechargeable ions and drugs enhance remineralization, hinder demineralization, and reduce microbial adhesion in difficult-to-access areas. Selection of denture base for clinical use will consider its ability to act as an ion/drug reservoir that is capable of release and recharge.

Macrophage Membrane-Coated Nano-Gemcitabine Promotes Lymphocyte Infiltration and Synergizes AntiPD-L1 to Restore the Tumoricidal Function.

The limited lymphocyte infiltration and exhaustion of tumoricidal functions in solid tumors remain a formidable obstacle to cancer immunotherapy. Herein, we designed a macrophage membrane-coated nano-gemcitabine system (MNGs) to promote lymphocyte infiltration and then synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes. MNGs exhibited effective intratumor-permeating and responsive drug-releasing capacity, produced notable elimination of versatile immunosuppressive cells, and promoted lymphocyte infiltration into cancer cell regions in tumors, but over 50% of these infiltrated lymphocytes were in the exhausted state. Compared with MNG monotherapy, the MNGs+antiPD-L1 combination produced 31.77% and 30.63% reduction of exhausted CD3+CD8+ T cells and natural killer (NK) cells and 2.83- and 3.17-fold increases of interferon-γ (IFN-γ)-positive subtypes, respectively, thereby resulting in considerable therapeutic benefits in several tumor models. Thus, MNGs provide an encouraging strategy to promote lymphocyte infiltration and synergize antiPD-L1 to restore their tumoricidal function for cancer immunotherapy.

An acid-labile bridged β-CD-based nano-hydrogel with superior anti-tumor drug delivery and release capacity

The traditional anti-tumor drugs are easily cleared during in vivo circulation and lack of targeting in chemotherapy, thus increasing their side effects and reducing their efficacy. Therefore, a novel acid-labile drug delivery system based on bridged β-cyclodextrins (β-CDs) nano-hydrogel was proposed. β-CD possesses good biocompatibility and hydrophilicity and can be chemically modified to construct a novel bridged complex via pH- responsive carbonic ester bond. In this study, doxorubicin (Dox) was used as an anti-tumor model drug and introduced into this acid-labile bridged β-CD-based nano-hydrogel via non-covalent interactions. The physicochemical properties of acid-labile bridged β-CD-based nano-hydrogel was characterized by 1Hnuclear magnetic resonance spectra (1HNMR), fourier transform infrared spectra (FTIR), transmission electron microscopy (TEM) and fluorescence spectroscopy. The cell viability and apoptosis of Dox loaded acid-labile bridged β-CD-based nano-hydrogel was obtained by cell counting kit-8 (CCK-8), fluorescence imaging and flow cytometry. The Dox loaded acid-labile bridged β-CD-based nano-hydrogel was stable in normal physiological environment and faster release at pH = 4.5 than that at pH = 7.4 and 9.1. The killing effect on cancerous cells was significantly enhanced in acidic medium compared with that in normal medium. This novel acid-labile bridged β-CD-based nano-hydrogel possesses biosafety and effective anti-cancer strategy, providing significant promising in future biomedical application.

Photothermal regulated multi-perceptive poly(ionic liquids) hydrogel sensor for bioelectronics

Hydrogels with excellent flexibility, water retention, and biocompatibility are natural carriers for drug delivery. However, the poor drug compatibility seriously limits the practical application of traditional PNIPAM-based hydrogel. Herein, a photothermal regulated smart hydrogel was synthesized by introducing poly(ionic liquids) chain into the binary polymer chain. The temperature-induced hydrophilic-hydrophobic switchable poly(ionic liquids) chain endows the smart hydrogel with editable transparency, enabling intuitive visualization of drug loading and releasing capacity. The smart hydrogel could be used as NIR/temperature-controlled drug carrier to achieve efficient and visualized release (40.8 % drug release rate in 30 min). Besides, the smart hydrogel sensor showed excellent strain sensing sensitivity (gauge factor = 3.73), short response time (116 ms), high durability (1800 s at 20 % strain), and impressive temperature sensing sensitivity (TCR = -1.252 %/°C). Based on the excellent sensing performance and editable drug-delivery ability, the smart hydrogel was assembled into a dynamic wound management system to realize personalized wound treatment and wireless state diagnosis. The wireless sensor early warning system could realize wireless monitoring and state warning of joints (fingers, ankles, and elbows), exhibiting guiding significance for rehabilitation treatment. Moreover, the high-resolution sensor array composed of 5 × 5 smart hydrogels could accurately identify the strain, temperature and NIR light in three-dimensional space and direction. In short, the smart hydrogel provides an innovative solution to personalized wound diagnosis and assisted rehabilitation.

Clove Oil-Nanostructured Lipid Carriers: A Platform of Herbal Anesthetics in Whiteleg Shrimp (Penaeus vannamei)

Whiteleg shrimp (Penaeus vannamei) have been vulnerable to the stress induced by different aquaculture operations such as capture, handling, and transportation. In this study, we developed a novel clove oil-nanostructured lipid carrier (CO-NLC) to enhance the water-soluble capability and improve its anesthetic potential in whiteleg shrimp. The physicochemical characteristics, stability, and drug release capacity were assessed in vitro. The anesthetic effect and biodistribution were fully investigated in the shrimp body as well as the acute multiple-dose toxicity study. The average particle size, polydispersity index, and zeta potential value of the CO-NLCs were 175 nm, 0.12, and −48.37 mV, respectively, with a spherical shape that was stable for up to 3 months of storage. The average encapsulation efficiency of the CO-NLCs was 88.55%. In addition, the CO-NLCs were able to release 20% of eugenol after 2 h, which was lower than the standard (STD)-CO. The CO-NLC at 50 ppm observed the lowest anesthesia (2.2 min), the fastest recovery time (3.3 min), and the most rapid clearance (30 min) in shrimp body biodistribution. The results suggest that the CO-NLC could be a potent alternative nanodelivery platform for increasing the anesthetic activity of clove oil in whiteleg shrimp (P. vannamei).

Microneedles for transdermal drug delivery using clay-based composites

Introduction Clays provide a powerful drug delivery system due to their specific structure, which can interact with drugs and control their release. Transdermal delivery avoids the transformation of a drug in the liver by dispensing the drug through the skin, avoiding the gastrointestinal tract. One of the most important and applicable clays in transdermal delivery is montmorillonite. Due to ion exchange and the multilayer structure of clay sheets, drugs are entrapped between the sheets, showing this material’s high drug release capacity. Recent studies have shown that the addition of 5 wt% clay is suitable for transdermal delivery applications. Areas covered In this review, we discussed clay-based polymer microneedles, mechanisms of clay-drug interactions, and antimicrobial effects of clays. We also investigated carriers for clay transdermal drug delivery and in vitro drug release from clay-drug composites. In addition, the most important clays, montmorillonite, halloysite, and sepiolite, were compared and discussed. Expert opinion The manufactured product represents an interesting method of sustained drug release through the skin. The duration of drug release can be tuned by modifying the polymer concentration and an appropriate molecular weight in the polymer system. When using clay as a non-polymer transdermal drug carrier, this adjustment is possible by changing the type and concentration of clay.

A multi-responsive targeting drug delivery system for combination photothermal/chemotherapy of tumor

To achieve efficient delivery and precise release of chemotherapy drugs at tumor sites, an active targeting multi-responsive drug delivery platform was developed. Here, doxorubicin hydrochloride (DOX) was loaded onto polydopamine (PDA), which were coated by the cystamine-modified hyaluronic acid (HA-Cys), designated as DOX@PDA-HA (PDH). The combination of PDA and HA-Cys endowed the nanoplatform photothermal conversion, tumor-targeting, and pH/redox/NIR sensitive drug release capacity. Moreover, HA could be degraded by the excess hyaluronidase (HAase) in the tumor microenvironment (TME), promoting DOX release, and further enhancing the effect of chemotherapy. Experimental results demonstrated PDH good biocompatibility, high loading rate, targeted drug delivery, and efficient tumor cell killing ability. This ingenious strategy based on PDH showed huge potential in photothermal/chemotherapy combination treatment of cancer.

Fabrication of biodegradable hydrogels based on chitosan and poly(azomethine‐urethane) containing phenyl triazine for drug delivery

AbstractA series of biodegradable hydrogels based on chitosan and polyurethanes was fabricated to be applied to the drug delivery application, and the fabricated hydrogels were characterized by using SEM, and FT‐IR techniques. Polyurethanes were also synthesized by using the different diisocyanates, and the diisocyanate's effect on the properties of the hydrogels was clarified. The mechanical and thermal properties, % swelling capacity, biodegradation, and hydrophilic or hydrophobic behaviors of the chitosan and polyurethane hydrogels were also clarified. The fabricated hydrogels were demonstrated good biodegradable and antibacterial behaviors. The cumulative drug release of the hydrogels was revealed that they have around 50% drug release capacity, and according to the obtained results, the chitosan and polyurethane‐based hydrogels have a potential drug delivery application of 5‐fluorouracil.

Drug-loaded mesoporous carbon with sustained drug release capacity and enhanced antifungal activity to treat fungal keratitis.

Fungal keratitis is a severe infectious corneal disease with a high rate of incidence and blindness. Since traditional treatments natamycin (NATA) eye drops, exhibit poor dissolution and bioavailability, and the efficacy of current therapeutic approaches remains limited. In this study, we innovatively utilized mesoporous carbon (Meso-C) and microporous carbon (Micro-C) as nanocarriers loaded with the antifungal drug NATA and silver nanoparticles (Ag-NPs). Porous carbon loaded with NATA and Ag-NPs has not previously been studied in fungal keratitis. Due to the mesoporous structure, high surface area and larger pore volume of Meso-C, it displayed greater superiority in sustained drug release and drug dispersity than Micro-C. Moreover, Meso-C could adsorb inflammatory cytokines during fungal infection. In vitro, Meso-C/NATA/Ag showed excellent antifungal effects. In vivo, compared with pure NATA treatment, Meso-C/NATA/Ag exhibited significantly improved therapeutic effects and reduced dosing frequency when treating fungal keratitis. Our study is the first to report the sustained drug release and improved drug dispersity of Meso-C/NATA and demonstrates that NATA and Ag-NPs-loaded Meso-C has therapeutic effects against fungal keratitis.

Investigation of Eutectic Mixtures of Fatty Acids as a Novel Construct for Temperature-Responsive Drug Delivery.

BackgroundMost of the traditional nanocarriers of cancer therapeutic moieties present dose-related toxicities due to the uptake of chemotherapeutic agents in normal body cells. The severe life-threatening effects of systemic chemotherapy are well documented. Doxorubicin, DOX is the most effective antineoplastic agent but with the least specific action that is responsible for severe cardiotoxicity and myelosuppression that necessitates careful monitoring while administering. Stimuli-sensitive/intelligent drug delivery systems, specifically those utilizing temperature as an external stimulus to activate the release of encapsulated drugs, have become a subject of recent research. Thus, it would be ideal to have a nanocarrier comprising safe excipients and controllable drug release capacity to deliver the drug at a particular site to minimize unwanted and toxic effects of chemotherapeutics. We have developed a simple temperature-responsive nanocarrier based on eutectic mixture of fatty acids. This study aimed to develop, physicochemically characterize and investigate the biological safety of eutectic mixture of fatty acids as a novel construct for temperature-responsive drug release potential.MethodsWe have developed phase change material, PCM, based on a series of eutectic mixtures of fatty acids due to their unique and attractive physicochemical characteristics such as safety, stability, cost-effectiveness, and ease of availability. The reversible solid-liquid phase transition of PCM is responsible to hold firm or actively release the encapsulated drug. The eutectic mixtures of fatty acids (stearic acid and myristic acid) along with liquid lipid (oleic acid) were prepared to exhibit a tunable thermoresponsive platform. Doxorubicin-loaded lipid nanocarriers were successfully developed with combined hot melt encapsulation (HME) and sonication method and characterized to achieve enhanced permeability and retention (EPR) effect-based solid tumor targeting in response to exogenous temperature stimulus. The cytotoxicity against melanoma cell lines and in vivo safety studies in albino rats was also carried out.ResultsDoxorubicin-loaded lipid nanocarriers have a narrow size distribution (94.59–219.3 nm), and a PDI (0.160–0.479) as demonstrated by photon correlation microscopy and excellent colloidal stability (Z.P value: −22.7 to −32.0) was developed. Transmission electron microscopy revealed their spherical morphology and characteristics of a monodispersed system. A biphasic drug release pattern with a triggered drug release at 41°C and 43°C and a sustained drug release was observed at 37°C. The thermoresponsive cytotoxic potential was demonstrated in B16F10 cancer cell lines. Hemolysis assay and acute toxicity studies with drug-free and doxorubicin lipid nanocarrier formulations provided evidence for their non-toxic nature.ConclusionWe have successfully developed a temperature-responsive tunable platform with excellent biocompatibility and intelligent drug release potential. The formulation components being from natural sources present superior characteristics in terms of cost, compatibility with normal body cells, and adaptability to preparation methods. The reported preparation method is adapted to avoid complex chemical processes and the use of organic solvents. The lipid nanocarriers with tunable thermoresponsive characteristics are promising biocompatible drug delivery systems for improved localized delivery of chemotherapeutic agents.

2D MXenes for combatting COVID-19 Pandemic: A perspective on latest developments and innovations

The COVID-19 pandemic has adversely affected the world, causing enormous loss of lives. A greater impact on the economy was also observed worldwide. During the pandemic, the antimicrobial aprons, face masks, sterilizers, sensor processed touch-free sanitizers, and highly effective diagnostic devices having greater sensitivity and selectivity helped to foster the healthcare facilities. Furthermore, the research and development sectors are tackling this emergency with the rapid invention of vaccines and medicines. In this regard, two-dimensional (2D) nanomaterials are greatly explored to combat the extreme severity of the pandemic. Among the nanomaterials, the 2D MXene is a prospective element due to its unique properties like greater surface functionalities, enhanced conductivity, superior hydrophilicity, and excellent photocatalytic and/or photothermal properties. These unique properties of MXene can be utilized to fabricate face masks, PPE kits, face shields, and biomedical instruments like efficient biosensors having greater antiviral activities. MXenes can also cure comorbidities in COVID-19 patients and have high drug loading as well as controlled drug release capacity. Moreover, the remarkable biocompatibility of MXene adds a feather in its cap for diverse biomedical applications. This review briefly explains the different synthesis processes of 2D MXenes, their biocompatibility, cytotoxicity and antiviral features. In addition, this review also discusses the viral cycle of SARS-CoV-2 and its inactivation mechanism using MXene. Finally, various applications of MXene for combatting the COVID-19 pandemic and their future perspectives are discussed.

Combinatorial Delivery of Gallium (III) Nitrate and Curcumin Complex-Loaded Hollow Mesoporous Silica Nanoparticles for Breast Cancer Treatment.

The main aims in the development of a novel drug delivery vehicle is to efficiently carry therapeutic drugs in the body’s circulatory system and successfully deliver them to the targeted site as needed to safely achieve the desired therapeutic effect. In the present study, a passive targeted functionalised nanocarrier was fabricated or wrapped the hollow mesoporous silica nanoparticles with 3-aminopropyl triethoxysilane (APTES) to prepare APTES-coated hollow mesoporous silica nanoparticles (HMSNAP). A nitrogen sorption analysis confirmed that the shape of hysteresis loops is altered, and subsequently the pore volume and pore diameters of GaC-HMSNAP was reduced by around 56 and 37%, respectively, when compared with HMSNAP. The physico-chemical characterisation studies of fabricated HMSNAP, Ga-HMSNAP and GaC-HMSNAP have confirmed their stability. The drug release capacity of the fabricated Ga-HMSNAP and GaC-HMSNAP for delivery of gallium and curcumin was evaluated in the phosphate buffered saline (pH 3.0, 6.0 and 7.4). In an in silico molecular docking study of the gallium-curcumin complex in PDI, calnexin, HSP60, PDK, caspase 9, Akt1 and PTEN were found to be strong binding. In vitro antitumor activity of both Ga-HMSNAP and GaC-HMSNAP treated MCF-7 cells was investigated in a dose and time-dependent manner. The IC50 values of GaC-HMSNAP (25 µM) were significantly reduced when compared with free gallium concentration (40 µM). The mechanism of gallium-mediated apoptosis was analyzed through western blotting and GaC-HMSNAP has increased caspases 9, 6, cleaved caspase 6, PARP, and GSK 3β(S9) in MCF-7 cells. Similarly, GaC-HMSNAP is reduced mitochondrial proteins such as prohibitin1, HSP60, and SOD1. The phosphorylation of oncogenic proteins such as Akt (S473), c-Raf (S249) PDK1 (S241) and induced cell death in MCF-7 cells. Furthermore, the findings revealed that Ga-HMSNAP and GaC-HMSNAP provide a controlled release of loaded gallium, curcumin and their complex. Altogether, our results depicted that GaC-HMNSAP induced cell death through the mitochondrial intrinsic cell death pathway, which could lead to novel therapeutic strategies for breast adenocarcinoma therapy.

Nanocomposite hydrogels for biomedical applications.

Nanomaterials' unique structures at the nanometer level determine their incredible functions, and based on this, they can be widely used in the field of nanomedicine. However, nanomaterials do possess disadvantages that cannot be ignored, such as burst release, rapid elimination, and poor bioadhesion. Hydrogels are scaffolds with three‐dimensional structures, and they exhibit good biocompatibility and drug release capacity. Hydrogels are also associated with disadvantages for biomedical applications such as poor anti‐tumor capability, weak bioimaging capability, limited responsiveness, and so on. Incorporating nanomaterials into the 3D hydrogel network through physical or chemical covalent action may be an effective method to avoid their disadvantages. In nanocomposite hydrogel systems, multifunctional nanomaterials often work as the function core, giving the hydrogels a variety of properties (such as photo‐thermal conversion, magnetothermal conversion, conductivity, targeting tumor, etc.). While, hydrogels can effectively improve the retention effect of nanomaterials and make the nanoparticles have good plasticity to adapt to various biomedical applications (such as various biosensors). Nanocomposite hydrogel systems have broad application prospects in biomedicine. In this review, we comprehensively summarize and discuss the most recent advances of nanomaterials composite hydrogels in biomedicine, including drug and cell delivery, cancer treatment, tissue regeneration, biosensing, and bioimaging, and we also briefly discussed the current situation of their commoditization in biomedicine.

Impact of drug carrier shape, size, porosity and blood rheology on magnetic nanoparticle-based drug delivery in a microvessel

Background and objectiveIn the drug targeting delivery, the mesoporous materials known as biomaterials exhibit a more significant drug loading and drug release capacity at a specific location are controlled by the external magnetic field. This article theoretically investigates the effects of a high specific surface, pore volume and unique pore size enrich mesoporous materials as carriers for magnetic drug targeting delivery. We analyze the trajectory of a porous drug carrier embedded with the magnetic nanoparticles are transported with the blood flow through the microvessel. MethodsThe governing equations for blood flow and the motion of the magnetic nanoparticles are solved analytically in terms of the Bessel function. The solutions have been computed numerically to discuss the effects of size and permeability of the carrier particle, the volume fraction of embedded magnetic nanoparticles, distance of the magnetic from the axis of the microvessel,the intensity of the magnetic field, blood rheology, the shape of the carrier particles and Saffman force on flow analysis. ResultsThe permeability of the drug carrier and the peripheral region support the drug carrier to capture near the tumor zone, while the stress jump is constant and Saffman parameter shows an opposite phenomenon. Due to symmetricity, the spherical particles easily capture at the tumor zone rather than the arbitrarily shaped drug carrier. Blood rheology based yield stress reduces the efficiency of the drug carrier to capture close to the tumor region. The trajectories of the drug carrier towards the tumor are restricted with an increase in the aspect ratio of the cylinder. The same phenomena are observed for the increased aspect ratio of the prolate ellipsoid. The outcomes of the present analysis will help to develop biomaterials in the drug delivery applications.

Preparation of Cross-linked Chitosan Quaternary Ammonium Salt Hydrogel Films Loading Drug of Gentamicin Sulfate for Antibacterial Wound Dressing.

Hydrogels, possessing high biocompatibility and adaptability to biological tissue, show great usability in medical applications. In this research, a series of novel cross-linked chitosan quaternary ammonium salt loading with gentamicin sulfate (CTMCSG) hydrogel films with different cross-linking degrees were successfully obtained by the reaction of chitosan quaternary ammonium salt (TMCS) and epichlorohydrin. Fourier transform infrared spectroscopy (FTIR), thermal analysis, and scanning electron microscope (SEM) were used to characterize the chemical structure and surface morphology of CTMCSG hydrogel films. The physicochemical property, gentamicin sulphate release behavior, cytotoxicity, and antibacterial activity of the CTMCSG against Escherichia coli and Staphylococcus aureus were determined. Experimental results demonstrated that CTMCSG hydrogel films exhibited good water stability, thermal stability, drug release capacity, as well as antibacterial property. The inhibition zone of CTMCSG hydrogel films against Escherichia coli and Staphylococcus aureus could be up to about 30 mm. Specifically, the increases in maximum decomposition temperature, mechanical property, water content, swelling degree, and a reduction in water vapor permeability of the hydrogel films were observed as the amount of the cross-linking agent increased. The results indicated that the CTMCSG-4 hydrogel film with an interesting physicochemical property, admirable antibacterial activity, and slight cytotoxicity showed the potential value as excellent antibacterial wound dressing.

Synthesis and characterization of hybrid nanocarrier layered double hydroxide grafted by polyethylene glycol and gemcitabine

For the past few years, organic-inorganic hybrid nanocarriers have been widely explored for effective drug delivery and preferable disease treatments. In this article, hydrothermal method was utilized to prepare fine dispersed layered double hydroxide (Mg-Al LDH) suspension. Polyethylene glycol (PEG) was grafted on the surface of LDH lamella in order to improve the dispersibility of LDH. Besides, the anti-cancer drug gemcitabine was grafted on the surface of LDH lamellas through chemical grafting. Hence a novel new type of organic-inorganic hybrid drug delivery system LDH-mPEG-Gemcitabine was obtained. In addition, the siRNA was intercalated into the LDH interlamination by ion exchange method to realize drug and gene co-delivery. The loading capacity of LDH and LDH-mPEG-Gemcitabine was evaluated by agarose gel electrophoresis. The characterization by laser particle size analyzer, TEM, FT-IR, XRD, in vitro cell viability and in vitro drug release demonstrated that LDH-mPEG-Gemcitabine possessed fine dispersibility, uniform morphology and particle size, fine biocompatibility, ideal drug loading and releasing capacity and held great potential to be used as a desired co-delivery system for drug and gene.

Drug-release dynamics and antibacterial activities of chitosan/cefazolin coatings on Ti implants

Chitosan/drug (cefazolin) coatings were synthesized on alkali-treated Ti surfaces via electrophoretic deposition to improve the antibacterial activities and corrosion resistances of the surfaces. The coatings exhibited desirable adhesion to the alkali-treated Ti due to the penetration of chitosan and drug into the pores of the substrates. The chitosan were cationic molecules which carried drug and both of them migrated toward the cathode during electrophoretic deposition. At a low potential, the drug dissolved in the chitosan film, whereas at a high potential, the drug aggregated into sheets on the surface of chitosan. The high potential provided the coating with high drug loading and releasing capacity. The total drug release of chitosan/drug coatings with 4.3 and 6.9 μm thickness in Hank's balanced salt solution (HBSS) was about 3 and more than 14 days, respectively. The coatings exhibited increased corrosion resistance than the Ti in HBSS evaluated via potentiostat. Additionally, the coating with high drug loading demonstrated approximate 100% antibacterial activities against Escherichia coli; thus, the proposed coatings can be used as promising Ti coatings to limit bacterial adhesion and proliferation.

Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy

BackgroundPhotodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy.ResultsThe designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo.ConclusionBCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.Graphic abstract

Suction Cups-Inspired Adhesive Patch with Tailorable Patterns for Versatile Wound Healing.

Medical patches play an important role in wound healing because of their tissue conformality, drug release capacity, and convenient operation. Great efforts have been devoted to developing new‐generation patches with distinctive features promoting wound healing. Here, inspired by the structure of octopus suction cups and the component of natural tissue, a biocompatible wound patch with selective adhesiveness and individualized design using a combined strategy of template‐replication and mask‐guided lithography is presented. Such patches are based on Ecoflex film with suction‐cup‐mimicking microstructures to adhere to normal skin and with biocompatible gelatin methacryloyl (GelMA) hydrogel to contact wounded areas. An ultraviolet mask with a tailorable pattern is employed to shape the GelMA hydrogel into customized geometry replicating individual wound areas, and thus both adhesion and antiadhesion properties are integrated into the same patch. In addition, vascular endothelial growth factor is loaded to accelerate the healing process. Based on these advantages, the authors demonstrate that the present patches not only adhere to different skin surfaces, but also promote the treatment of a rat cutaneous wound model. Thus, it is believed that this versatile patch can break through the limitation of traditional patches and be ideal candidates for wound healing and related biomedical applications.