Release Of Anticancer Drugs Research Articles

Biocompatible supramolecular hydrogels based on polysaccharide-modified hyaluronic acid for targeted delivering of doxorubicin

ABSTRACT In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.

An injectable dual-layer chitosan-alginate nano-hydrogel incorporated Cu(I)-isopolymolybdate-based metal-organic framework tailored for three-in-one anti-cancer nanotherapy

Designing potential agents and constructing hydrophilic nano-hydrogel platforms for biomedical and pharmaceutical applications, especially for polyoxometalate-based metal-organic frameworks (PMOF), present both great desirability and significant challenges. A unique open porous Cu(I)-isopolymolybdate-based metal-organic framework (CCUT) has been self-assembled through ionothermal processes for in vivo synergistic anti-cancer therapy. The periodicity of Drugs@CCUT-1 (nano-crystals of CCUT after cation exchange and anti-cancer drugs upload) has been investigated by synchrotron wide-angle X-ray scattering, confirming the lattice structure unchanged. To mitigate toxicity, enhance stimuli-responsive drug delivery, hydrophilicity, and biocompatibility, an injectable dual-layer chitosan//alginate-based nano-hydrogel is developed to incorporate Drugs@CCUT-1. Potential interactions between the chitosan layer and the surface of CCUT-1 have been analyzed by Density Functional Theory (DFT). Furthermore, the nanoparticles Drugs@CCUT-1@Gel exhibit efficient type I photodynamic therapy (PDT) and chemodynamic therapy (CDT) within the bio-window, effectively eradicating tumors in deep tissue. CCUT-1 generates a substantial amount of reactive oxygen species (ROS), stimulating the Keap1-Nrf2 signaling pathway and resulting in the expression of phase II enzymes, typically HO-1. CCUT-1@Gel not only demonstrates high capacity for anti-cancer drug upload and release, but also exhibits strong synergistic CDT/PDT in vivo anti-tumor efficacy. Hence, CCUT-1@Gel represents a promising in vivo nano-platform for synergistic chemotherapy (CT)/CDT/PDT three-in-one anti-cancer approach.

A biocompatible drug controlled release system based on β-cyclodextrin crosslinked magnetic lactose/ZIF-8 metal-organic frameworks for cancer treatment

Natural saccharides (Chitosan, Lactose, alginate, and β-cyclodextrin) have recently attracted much attention from researchers as drug delivery systems for cancer therapy. In this regard, for the first time, we designed a new targeted carrier based on magnetic lactose-modified ZIF-8 metal-organic frameworks crosslinked with β-cyclodextrin (M-Lactose@ZIF-8-β-CD) for the pH-responsive controlled release of anticancer drugs, hydrophilic doxorubicin (DOX), and hydrophobic curcumin (CUR) to MCF-7 breast cancer cells. The encapsulation efficiency of M-Lactose@ZIF-8-β-CD was found to be 95.16% for DOX and 65.01% for CUR. The in vitro release studies showed a pH-responsive controlled release of DOX and CUR from M-Lactose@ZIF-8-β-CD at pH 5, which confirmed the performance of the prepared carrier in the cancerous microenvironments. The release mechanism of both drugs was well described by the Korsmeyer-Peppas and Fickian diffusion. In addition, in vitro cytotoxicity, hemolysis, and antioxidant investigations clearly showed that the prepared M-Lactose@ZIF-8-β-CD carriers had good biocompatibility, high blood compatibility, and excellent antioxidant activity due to the presence of natural saccharides in carriers. Based on these findings, the M-Lactose@ZIF-8-β-CD can be applied as a promising targeted co-drug delivery carrier for cancer therapy.

Glycosylated AIE‐active Red Light‐triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy

AbstractPhotocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near‐infrared light‐triggered photolysis process of current photocage is largely singlet oxygen (1O2)‐dependent and lack of compatibility with other reactive oxygen species (ROS)‐activated techniques, which has proven to be the major bottleneck in achieving efficient and precise treatment. Herein, we reported a lactosylated photocage BT‐LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY‐TPE fluorophore via the superoxide anion radical (O2−⋅)‐cleavable thioketal bond for type I photodynamic therapy (PDT) and anticancer drug release. Amphiphilic BT‐LRC could be self‐assembled into aggregation‐induced emission (AIE)‐active nanoparticles (BT‐LRCs) owing to the regulation of carbohydrate‐carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates. BT‐LRCs could simultaneously generate abundant O2−⋅ through the aggregation modulated by lactose interactions, and DNA‐damaging agent CPT was subsequently and effectively released. Notably, the type I PDT and CPT chemotherapy collaboratively amplified the therapeutic efficacy in HepG2 cells and tumor‐bearing mice. Furthermore, the inherent AIE property of BT‐LRCs endowed the photocaged prodrug with superior bioimaging capability, which provided a powerful tool for real‐time tracking and finely tuning the PDT and photoactivated drug release behavior in tumor therapy.

Development of Chitosan-Coated Graphene Oxide and Iron Oxide Nanocomposites for Targeted Delivery of Camptothecin to Liver Cancer Cells.

Innovative drug delivery platforms for selective, regulated, and sustained release of anticancer drugs are crucial in cancer treatment. This study presents nanoparticles developed from chitosan (CS), graphene oxide (GO), and magnetite (Fe3O4), and their nanocomposites, to enhance the loading and release efficiency of camptothecin (CPT). Nanostructures were characterized using imaging microscopy, FT-IR, and X-ray diffraction, with an average crystallite size of 5.5 nm. Camptothecin binding proportions were 70% for CS, 81% for CS@Fe3O4, 58% for CS@GO, and 74% for CS@GO/Fe3O4. At pH 5.0, CPT release ratios were 87%, 80%, 88%, and 90%, respectively, and at pH 7.4, 84%, 72%, 89%, and 87%. Cytotoxicity was assessed using the MTT assay against HepG2 and SMMC-7721 cancer cells. CPT-CS@GO/Fe3O4 exhibited the highest survival at 5 µM and 12.5 µM concentrations, indicating it as the most effective nanocarrier for camptothecin delivery. The study demonstrates CS@GO/Fe3O4's potential as a superior drug delivery system.

Temperature-responsive two-dimensional polydopamine hydrogel: Preparation, mechanisms, and applications in cancer treatment

Temperature-responsive hydrogels are advanced materials that exhibit significant physical or chemical changes in response to temperature variations. When the temperature reaches a specific threshold, these hydrogels alter their properties accordingly. They offer significant advantages in cancer therapy, including precise control over drug release, minimized toxicity, improved therapeutic efficacy, and biodegradability. Advancing the development of novel temperature-responsive hydrogels is crucial for enhancing therapeutic strategies. Herein, two-dimensional polydopamine (2D PDA) was first combined with chitosan (CTS) to create a temperature-responsive hydrogel for the control and release of anticancer drugs. Leveraging the carbonyl-rich nature of 2D PDA, we initiated a reversible cyclization reaction between CTS and the carbonyl groups on the surface of 2D PDA, resulting in a temperature-responsive CTS@2D PDA (CP) hydrogel. Furthermore, the CP hydrogel template was incorporated with the photosensitizer zinc phthalocyanine (ZnPc) and sodium percarbonate (SPC), an oxygen (O2) donor, to form a composite hydrogel (CSZP hydrogel). O2 released from the CSZP hydrogel mitigated solid tumor hypoxia and suppressed the expression of hypoxia-inducible factor-1α (HIF-1α), thereby augmenting the efficacy of photodynamic therapy (PDT). This temperature-responsive hydrogel represented a highly promising platform for the precise and controlled release of various therapeutics, thereby advancing the field of targeted disease treatment.

Environmentally Friendly Synthesis of Gelatin Hydrogel Nanoparticles for Gastric Cancer Treatment, Bisphenol A Sensing and Nursing Applications: Fabrication, Characterization and ANN Modeling

This study presents a dual application approach for the environmentally friendly synthesis of gelatin hydrogel nanoparticles with potential applications in gastric cancer treatment, bisphenol A (BPA) sensing, and nursing. Gelatin hydrogel nanoparticles were synthesized using a green and freeze-drying method, avoiding the use of toxic chemicals and solvents. The nanoparticles showed excellent biocompatibility and promising potential for drug delivery system (DDS) in gastric cancer treatment. The controlled release of anticancer drugs from the gelatin nanoparticles was showed, highlighting their potential in targeted therapy. Additionally, the gelatin hydrogel nanoparticles were explored for BPA sensing. BPA is a widely used chemical known for its adverse effects on human health. The gelatin nanoparticles showed high selectivity and sensitivity towards BPA detection, making them suitable for environmental monitoring and health applications using scanning electron microscope (SEM). Also, in this study, an artificial neural network (ANN) was used to estimate the release of docetaxel (%) at 72 hours, the release of paclitaxel (%) at 72 hours, tensile strength with sample (wt%), and porosity (%) in broader ranges than the experimental samples. The environmentally friendly synthesis of gelatin hydrogel nanoparticles presented in this study offers a versatile platform with dual applications in gastric cancer treatment and sensing of harmful chemicals. The obtained results show the potential of these nanoparticles for innovative therapeutic and diagnostic strategies in healthcare and environmental monitoring. The study showed the development of sustainable and multifunctional nanomaterials for various biomedical applications. The modeling of the neural network predictions shows that increasing the sample (wt%) and porosity (%) leads to an increase in the release of docetaxel (%) at 72 hours, the release of paclitaxel (%) at 72 hours, and tensile strength. As porosity decreases, the release of docetaxel increases, and the release of paclitaxel and tensile strength also increase. Additionally, the prediction errors of the ANN in this study were evaluated using linear regression, showing acceptable error rates compared to the target results obtained from the experimental tests.

Oral delivery of Sunitinib malate using carboxymethyl cellulose/poly(acrylic acid-itaconic acid)/Cloisite 30B nanocomposite hydrogel as a pH-responsive carrier.

This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.

Core-Shell Microspheres with Encapsulated Gold Nanoparticle Carriers for Controlled Release of Anti-Cancer Drugs.

Cancer is one of the major threats to human health and lives. However, effective cancer treatments remain a great challenge in clinical medicine. As a common approach for cancer treatment, chemotherapy has saved the life of millions of people; however, patients who have gone through chemotherapy often suffer from severe side effects owing to the inherent cytotoxicity of anti-cancer drugs. Stabilizing the blood concentration of an anti-cancer drug will reduce the occurrence or severity of side effects, and relies on using an appropriate drug delivery system (DDS) for achieving sustained or even on-demand drug delivery. However, this is still an unmet clinical challenge since the mainstay of anti-cancer drugs is small molecules, which tend to be diffused rapidly in the body, and conventional DDSs exhibit the burst release phenomenon. Here, we establish a class of DDSs based on biodegradable core-shell microspheres with encapsulated doxorubicin hydrochloride-loaded gold nanoparticles (DOX@Au@MSs), with the core-shell microspheres being made of poly(lactic-co-glycolic acid) in the current study. By harnessing the physical barrier of the biodegradable shell of core-shell microspheres, DOX@Au@MSs can provide a sustained release of the anti-cancer drug in the test duration (which is 21 days in the current study). Thanks to the photothermal properties of the encapsulated gold nanoparticle carriers, the core-shell biodegradable microspheres can be ruptured through remotely controlled near-infrared (NIR) light, thereby achieving an NIR-controlled triggered release of the anti-cancer drug. Furthermore, the route of the DOX-Au@MS-enabled controlled release of the anti-cancer drug can provide durable cancer cell ablation for the long period of 72 h.

Effect of Periodate-Induced Cross-linking on Dual Anticancer Drug Release from Poly(2-isopropyl-2-oxazoline)/Tannic Acid-Based Layer-by-Layer Microparticles.

This study reports, first, on the preparation and cross-linking of multilayers composed of poly(2-isopropyl-2-oxazoline-co-ethyleneimine) (PiPOX-PEI) and tannic acid (TA). PiPOX was synthesized by cationic ring-opening polymerization (CROP) and partially hydrolyzed, yielding a random copolymer PiPOX-PEI. It was then coassembled at the surface with TA using the layer-by-layer (LbL) technique. Multilayers were exposed to NaIO4 solution to induce covalent bond formation between PEI units of PiPOX-PEI and TA. Cross-linking with NaIO4 enhanced the stability of the multilayers, especially under basic conditions. Second, the potential of PiPOX-PEI and TA multilayers as a stimuli-responsive dual drug-releasing platform was examined using curcumin (CUR) and doxorubicin (DOX) as model drugs. These drugs were chosen as they can act in a combinatorial manner to increase cell death. The surface of CUR-containing CaCO3 microparticles was modified with PiPOX-PEI and TA multilayers and postloaded with DOX. We found that LbL particles could release DOX in a pH-responsive manner, whereas temperature-induced release was observed only when the temperature was raised above 40 °C. The DOX and CUR released from the LbL particles could act synergistically on HCT-116 cells. Cross-linking increased the DOX release from LbL particles but decreased the CUR release from the core. Corroborating the release data, the synergy observed with the non-cross-linked particles was lost with the cross-linked particles, and the decrease in the viability of HCT-116 cells was attributed mainly to the release of DOX. Overall, we describe here NaIO4-induced cross-linking of PiPOX-PEI/TA LbL films, the effects of pH, temperature, and cross-linking on DOX and CUR release from multilayers, and comparison of the combinatorial effect of DOX and CUR for cross-linked and non-cross-linked LbL microparticles through cell viability assays.

Glycosylated AIE-active Red Light-triggered Photocage with Precisely Tumor Targeting Capability for Synergistic Type I Photodynamic Therapy and CPT Chemotherapy.

Photocaging is an emerging protocol for precisely manipulating spatial and temporal behaviors over biological activity. However, the red/near-infrared light-triggeredphotolysis process of current photocage is largely singlet oxygen (1O2)-dependent and lack of compatibility with other reactive oxygen species (ROS)-activated techniques, which has proven to be the major bottleneck in achieving efficient and precise treatment. Herein, we reported a lactosylated photocage BT-LRC by covalently incorporating camptothecin (CPT) into hybrid BODIPY-TPE fluorophore via the superoxide anion radical (O2-•)-cleavable thioketal bond for type I photodynamic therapy (PDT) and anticancer drug release. Amphiphilic BT-LRC could be self-assembled into aggregation-induced emission (AIE)-active nanoparticles (BT-LRCs) owing to the regulation of carbohydrate-carbohydrate interactions (CCIs) among neighboring lactose units in the nanoaggregates. BT-LRCs could simultaneouslygenerate abundant O2-• through the aggregation modulated by lactose interactions, and DNA-damaging agent CPT was subsequently and effectively released. Notably, the type I PDT and CPT chemotherapy collaboratively amplified the therapeutic efficacy in HepG2 cells and tumor-bearing mice. Furthermore, the inherent AIE property of BT-LRCs endowed the photocaged prodrug with superior bioimaging capability, which provided a powerful tool for real-time tracking and finely tuning the PDT and photoactivated drug release behavior in tumor therapy.

In-situ forming Cu-based metal-organic framework in the presence of chitosan-Fe3O4 nanohybrids: A pH-sensitive carrier for controlled release of doxorubicin

In recent years, stimuli-responsive drug delivery systems based on pH, particularly those developed using bio-derived nanocomposite systems, have gained significant attention. In this work, a novel magnetic carrier was designed based on biopolymeric chitosan and metal-organic framework (MOF) for pH-controlling the release of anticancer drugs. To end this, an in-situ green method was performed to form Cu-based MOF in the presence of a magnetic polysaccharide synthesized by precipitation method toward the construction of CS/Fe3O4/Cu-MOF nanocomposite. The nanocomposite was immersed in an aqueous solution of a model anticancer drug, doxorubicin (DOX), and a higher loading capacity (90.1 ± 0.5 %) was achieved. The in-vitro drug release study showed low release rates in simulated physiological environments (pH 7.4, 37 °C, lower than about 20 %), but higher release rates in tumor tissue conditions (pH 4.5, 41 °C, higher than about 60 %) over 96 h, allowing for sustained and extended delivery of DOX. Additionally, the MTT assay demonstrated that the blank and DOX-loaded CS/Fe3O4/Cu-MOF had good cytocompatibility (over 80 % cell viability) and considerable cytotoxicity (lower than 40 % at 16 μg/mL) toward breast cancer (MCF-7) cell line, respectively. These results indicated that the synthesized nanocomposite with suitable pH-sensitivity has potential as a targeted anticancer agent.

Drug-loaded nanoparticles for cancer therapy: a high-throughput multicellular agent-based modeling study.

Interactions between biological systems and engineered nanomaterials have become an important area of study due to the application of nanomaterials in medicine. In particular, the application of nanomaterials for cancer diagnosis or treatment presents a challenging opportunity due to the complex biology of this disease spanning multiple time and spatial scales. A system-level analysis would benefit from mathematical modeling and computational simulation to explore the interactions between anticancer drug-loaded nanoparticles (NPs), cells, and tissues, and the associated parameters driving this system and a patient's overall response. Although a number of models have explored these interactions in the past, few have focused on simulating individual cell-NP interactions. This study develops a multicellular agent-based model of cancer nanotherapy that simulates NP internalization, drug release within the cell cytoplasm, "inheritance" of NPs by daughter cells at cell division, cell pharmacodynamic response to the intracellular drug, and overall drug effect on tumor dynamics. A large-scale parallel computational framework is used to investigate the impact of pharmacokinetic design parameters (NP internalization rate, NP decay rate, anticancer drug release rate) and therapeutic strategies (NP doses and injection frequency) on the tumor dynamics. In particular, through the exploration of NP "inheritance" at cell division, the results indicate that cancer treatment may be improved when NPs are inherited at cell division for cytotoxic chemotherapy. Moreover, smaller dosage of cytostatic chemotherapy may also improve inhibition of tumor growth when cell division is not completely inhibited. This work suggests that slow delivery by "heritable" NPs can drive new dimensions of nanotherapy design for more sustained therapeutic response.

Enzyme-Triggered Degradation of Supramolecularly Cross-Linked Polymersomes of Azobenzene-Based Polyurethane: Cell-Selective Anticancer Drug Release.

Enzyme-responsive self-assembled nanostructures for drug delivery applications have gained a lot of attention, as enzymes exhibit dysregulation in many disease-associated microenvironments. Azoreductase enzyme levels are strongly elevated in many tumor tissues; hence, here, we exploited the altered enzyme activity of the azoreductase enzyme and designed a main-chain azobenzene-based amphiphilic polyurethane, which self-assembles into a vesicular nanostructure and is programmed to disassemble in response to a specific enzyme, azoreductase, with the help of the nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme in the hypoxic environment of solid tumors. The vesicular nanostructure sequesters, stabilizes the hydrophobic anticancer drug, and releases the drug in a controlled fashion in response to enzyme-triggered degradation of azo-bonds and disruption of vesicular assembly. The biological evaluation revealed tumor extracellular matrix pH-induced surface charge modulation, selective activated cellular uptake to azoreductase overexpressed lung cancer cells (A549), and the release of the anticancer drug followed by cell death. In contrast, the benign nature of the drug-loaded vesicular nanostructure toward normal cells (H9c2) suggested excellent cell specificity. We envision that the main-chain azobenzene-based polyurethane discussed in this manuscript could be considered as a possible selective chemotherapeutic cargo against the azoreductase overexpressed cancer cells while shielding the normal cells from off-target toxicity.

Self-healable, stimuli-responsive bio-ionic liquid and sodium alginate conjugated hydrogel with tunable Injectability and mechanical properties for the treatment of breast cancer

Designing stimuli-responsive drug delivery vehicles with higher drug loading capacity, sustained and targeted release of anti-cancer drugs and able to mitigate the shortcomings of traditional systems is need of hour. Herein, we designed stimuli-responsive, self-healable, and adhesive hydrogel through synergetic interaction between [Cho][Gly] (Choline-Glycine) and sodium alginate (SA). The hydrogel was formed as a result of non-covalent interaction between the components of the mixture forming the fibre kind morphology; confirmed through FTIR/computational analysis and SEM/AFM images. The hydrogel exhibited excellent mechanical strength, self-healing ability, adhesive character and most importantly; adjustable injectability. In vitro biocompatibility of the hydrogel was tested on HaCaT and MCF-7 cells, showing >92 % cell viability after 48 h. The hemolysis ratio (<4 %) of the hydrogel confirmed the blood compatibility of the hydrogel. When tested for drug-loading capacity, the hydrogel show 1500 times drug loading for the 5-fluorouracil (5-FU) against the SA based hydrogel. In vitro release data indicated that 5-FU have more preference towards the cancerous cell condition, i.e. acidic pH (>85 %), whereas the drug-loaded hydrogel successfully killed the MCF-7 and HeLa cell with a <IC50–1.92 mM value. The studied hydrogel paves way towards controlled and sustained delivery of anti-cancer drug for the treatment of breast cancer.

Thermo-responsive composite nanoparticles based on hydroxybutyl chitosan oligosaccharide: Fabrication, stimulus release and cancer therapy

Designing thermo-responsive nanocarriers based on biopolymers is fascinating and challenging for cancer therapy. In this study, thermo-responsive composite nanoparticles (CNPs) were prepared using hydroxybutyl chitosan oligosaccharide (HBCOS) and sodium caseinate (SC) via electrostatic interactions and covalent crosslinking. The temperature-responsive behaviors of CNPs were induced by the breakage of hydrogen bonds and the shrinkage of chains in nanoparticles. The CNPs exhibited concentration-independent thermo-responsive behavior, non-adsorption aggregation, and non-hemolysis, suggesting excellent stability and thermo-sensitivity. The initial release rate and final amount of DOX released from CNPs at 42 °C were higher than that at 37 °C, showing a thermo-responsive release, which was also more prominent at lower pH. The release of DOX from CNPs followed first order kinetics based on Fickian diffusion. In vitro cytotoxicity assays confirmed the thermo-responsive antitumor activity of DOX-loaded CNPs as the HT-29 cell viability incubated with DOX-loaded CNPs at 42 °C was significantly lower than that at 37 °C. Cellular uptake experiments proved that DOX-loaded CNPs accumulated in the cytoplasm after being endocytosed and promoted DOX release by increasing environment temperature. This study generated stable thermo-sensitive CNPs based on biopolymers, which can be used as potential nanocarriers for the controlled release of anticancer drugs for cancer therapy.

The Effect of Co-Delivery of Oxygen and Anticancer Drugs on the Viability of Healthy and Cancer Cells under Normoxic and Hypoxic Conditions.

Hypoxia, cancer, tissue damage, and acidic pH conditions are interrelated, as chronic hypoxic conditions enhance the malignant phenotype of cancer cells, causing more aggressive tissue destruction, and hypoxic cells rely on anaerobic glycolysis, leading to the accumulation of lactic acid. Therefore, the administration of oxygen is necessary to support the functions of healthy cells until the formation of new blood vessels and to increase the oxygen supply to cancerous tissues to improve the efficacy of antitumor drugs on tumor cells. In addition to O2 supply, pH-dependent delivery of anticancer drugs is desired to target cancer cells and reduce drug side effects on healthy cells. However, the simultaneous delivery of O2 and pH-dependent anticancer drugs via nanomaterials and their effects on the viability of normal and cancer cells under hypoxic conditions have not been studied in sufficient numbers. This study describes the synthesis of a pH-responsive nanomaterial containing oxygen and anticancer drugs that exhibits sustained O2 release over a 14 d period under hypoxic conditions and pH-dependent sustained release of anticancer drugs over 30 d. The simultaneous administration of O2 and anticancer drugs results in higher cell survival of normal cells than that of cancer cells under hypoxic and normoxic conditions.

Synthesis of silver nanocomposite semi-interpenetrating polymer network hydrogel based on sodium alginate-g-polyacrylamide for using in Epirubicin anticancer drug release

Synthesis of silver nanocomposite semi-interpenetrating polymer network hydrogel based on sodium alginate-g-polyacrylamide for using in Epirubicin anticancer drug release

Chitosan‐based pH‐sensitive antibacterial bionanocomposites with laponite immobilized silver nanoparticles for delivery of sunitinib maleate to breast cancers

In this work, new pH‐sensitive and antibacterial drug carrier systems based on silver nanoparticles (AgNPs) embedded in the interlayer of laponite (Lap) in the presence of chitosan (CTS) for the controllable release of sunitinib maleate (STM) were developed. Silver ions and sunitinib maleate were first loaded into Lap, and the CTS‐based hybrid bionanocomposite carrier (Lap@CTS@AgNPs@STM) was obtained in the presence of citric acid as a cross‐linker agent. The successful preparation of nanocarrier and Ag NPs formation was thoroughly confirmed using techniques such as FTIR, XRD, TGA, SEM, and TEM. TEM images illustrated the excellent distribution of Ag NPs in the structure of Lap@CTS@AgNPs. The as‐prepared samples showed a pH‐sensitive anticancer drug release behavior. The STM release mechanism was studied using Korsmeyer–Peppas and Higuchi kinetic models. Furthermore, the in vitro cytotoxicity and antibacterial tests were carried out against both bacteria S. aureus and E. coli and MCF‐7 cell lines, respectively, to prove the effectiveness of synthesized samples as multifunctional carrier systems for biomedical applications.

The impact of cationic/anionic ratio on the physicochemical aspects of catanionic niosomes as a promising carrier for anticancer drugs

BackgroundNiosomes are adaptable nanocarriers for the delivery and controlled release of anticancer drugs. The addition of ionic surfactants could easily functionalize these carriers. Catanionic niosomes that are comprised of cationic and anionic surfactants are effective drug-delivery vehicles. Here, we aim to evaluate the impact of the cationic/anionic ratio on the noisome characteristics. MethodsA novel approach utilizing molecular modeling was utilized to analyze some characteristics of catanionic niosomes, showing great potential as a vehicle for anticancer drugs. The nonionic surfactant SPAN60, along with cholesterol as the stabilizer, was utilized in the study. Moreover, CTAB and SDS were used as positively and negatively charged surfactants, respectively. An FDA-approved c-Met inhibitor, cabozantinib, was selected as the drug. Several significant parameters associated with the cabozantinib molecule and its properties within the bilayer like hydrogen bonding, total energy, radius of gyration (Rgyr), diffusion coefficient, and radial distribution function (RDF). ResultsThe findings suggest that the cabozantinib’s hydrogen bonding plays a vital role in the drug’s movement through the bilayer. The CTAB-rich niosomes showed a higher number of hydrogen bonds compared to the SDS-rich formulations. The diffusion coefficient was in agreement with the number of H-bonding, and this value increased from 3.12 × 10-12 (m2/s) in CTAB-rich niosome to 7.66 × 10-12 (m2/s) in SDS-rich niosime. ConclusionThe total binding energy between the drug and bilayer components can control drug release. The computational approach could sufficiently describe the influence of cationic/anionic molar ratios on the bilayer features, and the characteristics of catanionic niosomes could be easily adjusted for the controlled release of anticancer drugs.