High Loading Efficiency Research Articles

Comparative in-vitro and in-vivo evaluation of spherulites and cubosomes of Irinotecan for lung targeting.

The present investigation aimed at the comparative evaluation of the developed nanocarriers, viz. spherulites and cubosomes for lung targeting. Both the spherulites and cubosomes were characterized for their entrapment efficiency, drug loading, size and zeta potential, in-vitro drug release profile, surface morphology, hemocompatibility, and in-vivo pharmacokinetic and lung biodistribution. The optimized batches of spherulites and cubosomes possessed high entrapment efficiency and drug loading with size around 200 nm, which is suitable for lung targeting. The zeta potential value for both the nanoformulations was found to be between -20 and -30 mv indicating the physical stability against aggregation. The SEM and TEM analysis revealed the presence of spherical and discrete particles in both the types of nanocarriers. Water channels were observed in case of cubosomes. Spherulites and cubosomes showed pH-dependent drug release with lower release at physiological pH while higher release at the pH of the tumor microenvironment. Both spherulites and cubosomes exhibited highly significant increase in the half-life and mean residence time in the plasma. The prepared nanoformulations were hemocompatible and had higher lung targeting potential compared to the plain drug solution.

Development of a phosphoaminopyrazine-loaded cellulose nanoparticle drug delivery system for targeted treatment of triple-negative breast cancer.

This study explores the development of a sustainable drug delivery system using cellulose nanoparticles (CNPs) derived from potato pulp for the controlled release of phosphoaminopyrazine (PAP), a promising anticancer agent. CNPs were synthesized via nanoprecipitation, and PAP was loaded through in-situ nanoprecipitation, achieving a high loading efficiency of 79.2 %. Characterization of CNPs and PAP-loaded CNPs (PAP@CNP) using Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and thermogravimetric analysis (TGA) confirmed the structural integrity, spherical morphology (45.33 nm for CNPs, 54.6 nm for PAP@CNP), and enhanced thermal stability of PAP@CNP. In vitro, drug release studies demonstrated sustained release over 48 h, with pH-sensitive kinetics favoring the acidic tumor microenvironment. Cytotoxicity assays revealed superior efficacy of PAP@CNP against triple-negative breast cancer cells (MDA-MB-231; IC50 = 20.86 ± 0.81 μg/mL) compared to cisplatin while showing minimal toxicity to normal human umbilical vein endothelial cells (HUVECs). Cellular uptake studies using epifluorescence microscopy and flow cytometry confirmed time-dependent internalization and intracellular drug release. Potato pulp, an abundant agro-industrial waste, as a renewable source for CNPs highlights this approach's economic and environmental advantages. This study demonstrates the potential of potato pulp-derived CNPs as a sustainable and cost-effective platform for targeted cancer therapy; offering improved therapeutic outcomes and reduced environmental impact.

Advances in Pure Drug Self-Assembled Nanosystems: A Novel Strategy for Combined Cancer Therapy.

Nanoparticle-based drug delivery systems hold great promise for improving the effectiveness of anti-tumor therapies. However, their clinical translation remains hindered by several significant challenges, including intricate preparation processes, limited drug loading capacity, and concerns regarding potential toxicity. In this context, pure drug-assembled nanosystems (PDANSs) have emerged as a promising alternative, attracting extensive research interest due to their simple preparation methods, high drug loading efficiency, and suitability for large-scale industrial production. This innovative approach presents new opportunities to enhance both the safety and therapeutic efficacy of cancer treatments. This review comprehensively explores recent progress in the application of PDANSs for cancer therapy. It begins by detailing the self-assembly mechanisms and fundamental principles underlying PDANS formation. The discussion then advances to strategies for assembling single pure drug nanoparticles, as well as the co-assembly of multiple drugs. Subsequently, the review addresses the therapeutic potential of PDANSs in combination treatment modalities, encompassing diagnostic and therapeutic applications. These include combinations of chemotherapeutic agents, phototherapeutic approaches, the integration of chemotherapy with phototherapy, and the synergistic use of immunotherapy with other treatment methods. Finally, the review highlights the potential of PDANSs in advancing tumor therapy and their prospects for clinical application, providing key insights for future research aimed at optimizing this technology and broadening its utility in cancer treatment.

Optimizing etodolac and quercetin loaded MSNs using taguchi design: an approach for enhancing drug loading efficiency.

The application of mesoporous silica nanoparticles (MSN) as a drug carrier system got immense attention in the past few years due to their exceptional high drug loading efficiency. However, the process of drug loading is quite challenging compared to other lipid-based drug delivery systems. Hence, the MSNs using different catalysts were synthesized, and their mesoporous material characteristic was confirmed by the type IV adsorption-desorption isotherm using BET analyzer. The effect of solvent selection and other process parameters (drug to MSNs ratio, period of loading, and stirring speed) on the loading of BCS class II and IV model drugs etodolac(ETD) and quercetin(QUR) respectively were investigated with the help of Taguchi DOE. The predicted value for the highest % drug loading was close to the experimental value(19.04 ± 0.50 % and 11.40 ± 0.18 % for ETD and QUR respectively). It was interesting to note, that the solvent selection had the highest impact on the drug loading of ETD into the MSNs, whereas for QUR this parameter was insignificant. Hence reflecting that a generalized procedure for the drug loading into the MSNs cannot be followed and had to be critically studied. Also, the loading of ETD and QUR into the MSNs improved the aqueous solubility (3.08 and 2.5 folds respectively). Further the in-vitro drug release properties were evaluated for ETD and QUR from MSNs in various drug release mediums to explore their release mechanism from MSNs using in vitro drug release kinetic modelling.

A Multifunctional MIL-101-NH2(Fe) Nanoplatform for Synergistic Melanoma Therapy.

Melanoma is an aggressive form of skin cancer, and single-modality treatments often fail to prevent tumor recurrence and metastasis. Combination therapy has emerged as an effective approach to improve treatment outcomes. In this study, we developed a multifunctional nanoplatform, MIL@DOX@ICG, utilizing MIL-101-NH2(Fe) as a carrier to co-deliver the chemotherapeutic agent doxorubicin (DOX) and the photosensitizer indocyanine green (ICG). MIL-101-NH2(Fe) was synthesized via a hydrothermal method. Drug release was evaluated under different pH conditions, and the photothermal effect was tested under near-infrared (NIR) laser irradiation. Hydroxyl radical and reactive oxygen species generation capacities were quantified. Cellular studies using B16F10 cells assessed cytotoxicity, cellular uptake, migration inhibition, and colony formation suppression. In vivo experiments in melanoma-bearing mice evaluated antitumor efficacy and systemic safety through tumor growth inhibition, histological analyses, and toxicity assessments. MIL@DOX@ICG exhibited a uniform octahedral structure with a particle size of approximately 139 nm and high drug loading efficiencies for DOX (33.70%) and ICG (30.59%). The nanoplatform demonstrated pH-responsive drug release and potent photothermal effects. The generation of hydroxyl radicals via the Fenton reaction and reactive oxygen species production under NIR laser irradiation by MIL@DOX@ICG were confirmed. In vitro assessments revealed significant cytotoxicity of MIL@DOX@ICG against B16F10 cells under NIR laser irradiation, with improved efficacy in inhibiting cell proliferation and migration. In vivo studies confirmed the superior antitumor efficacy of MIL@DOX@ICG + NIR treatment, synergistically harnessing chemotherapy, photothermal therapy, photodynamic therapy, and chemodynamic therapy effects while maintaining excellent biocompatibility. Our findings underscore the potential of MIL-101-NH2(Fe) nanoparticles as a versatile and effective platform for synergistic melanoma therapy, offering a promising strategy for overcoming the limitations of conventional treatment modalities.

Albumin/Hyaluronic Acid Nanoparticle-Laden Contact Lenses for the Ocular Delivery of 5-Fluorouracil.

Nanoparticle-laden contact lenses are a formidable strategy for ocular drug delivery. However, incorporating nanoparticles to achieve sustained drug release without affecting the contact lenses' properties remains a challenging task. In this work, daily and monthly replacement silicone-hydrogel contact lenses laden with bovine serum albumin/hyaluronic acid (BSA/HA) nanoparticles are presented. These nanoparticle-laden contact lenses enable the sustained release of 5-fluorouracil (5-FU) in mimetic physiological conditions. The nanoparticle-laden contact lenses display properties similar to neat contact lenses, including refractive index, water content, UV/visible transmittance and chemical structure. Noteworthy attributes include the BSA/HA nanoparticles' low polydispersity, negative surface charge and a hydrodynamic size of ~210 nm, as well as the high nanoparticle loading efficiency (~ 30%) of the contact lenses. Thereby, the BSA/HA nanoparticles are a promising strategy for developing nanoparticle-laden contact lenses for therapeutic applications, namely for sustained drug delivery.

Fabrication of glipizide loaded polymeric microparticles; in-vitro and in-vivo evaluation.

Controlled-release microparticles offer a promising avenue for enhancing patient compliance and minimizing dosage frequency. In this study, we aimed to design controlled-release microparticles of Glipizide utilizing Eudragit S100 and Methocel K 100 M polymers as controlling agents. The microparticles were fabricated through a simple solvent evaporation method, employing various drug-to-polymer ratios to formulate different controlled-release batches labeled as F1 to F5. Evaluation of the microparticles encompassed a range of parameters including flow properties, particle size, morphology, percentage yield, entrapment efficiencies, percent drug loading, and dissolution studies. Additionally, various kinetic models were employed to elucidate the drug release mechanism. Furthermore, difference and similarity factors were utilized to compare the dissolution profiles of the tested formulations with a reference formulation. The compressibility index and angle of repose indicated favorable flow properties of the prepared microparticles, with values falling within the range of 8 to 10 and 25 to 29, respectively. The particle size distribution of the microparticles ranged from 95.3 to 126 μm. Encouragingly, the microparticles exhibited high percent yield (ranging from 66 to 77%), entrapment efficiency (80 to 96%), and percent drug loading (46 to 54%). All formulated batches demonstrated controlled drug release profiles extending up to 12 hours, with glipizide release following an anomalous non-Fickian diffusion pattern. However, the drug release profiles of the reference formulation and various polymeric microparticles did not meet the acceptable limits of difference and similarity factors. In-vivo studies revealed sustained hypoglycemic effects over a 12-hour period, indicating the efficacy of the controlled-release microparticles. Overall, our findings suggest the successful utilization of polymeric materials in designing controlled-release microparticles, thereby reducing dosage frequency and potentially improving patient compliance.

X-ray-Triggered Activation of Polyprodrugs for Synergistic Radiochemotherapy.

X-ray-induced photodynamic therapy (XPDT) can penetrate deeply into the tumor tissues to overcome the disadvantage of conventional PDT. However, the therapeutic efficacy of XPDT in cancer therapy is still restricted due to the insufficient reactive oxygen species (ROS) generation at a relatively low irradiation dosage. Herein, we present the tumor pH and ROS-responsive polyprodrug micelles to load the X-ray photosensitizer verteporfin (VP) as an ROS production enhancer. The block copolymer polyprodrug consisting of hydrophilic poly(ethylene glycol) (PEG) as well as the segments of thioketal-linked camptothecin (CPT) methacrylate (CPTKMA) and 2-(pentamethyleneimino)ethyl methacrylate (PEMA) (PEG-b-P(CPTKMA-co-PEMA)) can self-assemble into micelles in aqueous solution and encapsulate VP with a high loading efficiency of 67%. Inside tumor tissues, the zeta potential of the micelles can transform from neutral to positive for promoted cellular internalization under tumor acidity. Followed by X-ray irradiation at the dose of 4 Gy, efficient ROS generation in the presence of VP triggers CPT release. The VP-loaded polyprodrug micelles can finally ablate tumors efficiently via synergistic radiochemotherapy due to deep penetration of X-ray inside tumor tissues, ROS generation enhancement, and triggered CPT release. Consequently, this promising strategy represents a robust therapeutic modality for the enhanced radiochemotherapy of cancers.

Research progress in polysaccharide-modified lipid nanoparticles for drug delivery

Lipid nanoparticles serve as a promising drug delivery system due to the good biocompatibility, non-immunogenicity, and high drug loading efficiency. However, unmodified lipid nanoparticles have limitations such as poor stability, easy hydrolysis, and rapid removal. To overcome these shortcomings, researchers have developed peptide modification, antibody modification, ligand modification, nucleic acid aptamer modification, and polysaccharide modification for lipid nanoparticles. Polysaccharides are a class of natural polymers, and the polysaccharide-modified lipid nanoparticles exhibit good biocompatibility, precise targeting, and low toxicity. Therefore, polysaccharide-modified lipid nanoparticles demonstrate great potential in clinical treatment. This review summarizes the preparation and application of polysaccharide-modified lipid nanoparticles, aiming to provide a reference for further research and development of new lipid nanoparticles.

Organelle-Level Trafficking and Metabolism Kinetics for Redox-Responsive Paclitaxel Prodrug Nanoparticles Characterized by Experimental and Modeling Analysis.

Redox-responsive self-assembled prodrug nanoparticles have received extensive attention for their high loading efficiency and environmentally responsive properties. However, the intracellular metabolism and transportation kinetics were poorly understood, which limited the rational design and development of this delivery system. Herein, tetraphenylporphyrin-paclitaxel (TxP) prodrugs with thioether, disulfide, and dicarbon linkers (TsP, TssP, and TccP) were synthesized and self-assembled as nanoparticles. The redox responsiveness was investigated both in the simulated medium and in tumor cells via mass spectrometry. TxP NP and PTX concentrations in 4T1 whole cells, endosomal systems, and cytoplasm over time were quantified by UPLC-MS/MS and modeled using the nonlinear mixed effect (NLME) approach. Cytotoxicity was studied in 4T1 and MCF-7 cell lines, and antitumor efficacy was analyzed in 4T1 tumor-bearing mice. Mass spectrometry identified both oxidative and reductive metabolites in redox simulants for TssP NPs and TsP NPs. In 4T1 cells, only reductive metabolites for TssP NPs were detected, while both oxidative and reductive metabolites for TsP NPs were detected. The developed subcellular pharmacokinetic model suggested that the estimated metabolism rates of TxP NPs in endosomal systems were 10 to 27 times of the rates in cytoplasm, indicating that endosomal systems were the dominant place for intracellular metabolism. These rates were numerically higher for TsP NPs than TssP NPs in endosomal systems (1.7-fold) and the cytoplasm (2.5-fold). The internalization of nanoparticles was identified to be slow (kmax,int, 0.015 h-1) and saturable. The transportation rate constant across the endosomal membranes was fast for PTX (27.1 h-1) and slow for TxP NPs (0.098 h-1). TsP and TssP NPs had comparable in vivo antitumor efficacy, which was higher than that of TccP NPs. This study quantified the organelle-level transportation and metabolism kinetics for three prodrug nanoparticles with redox-responsive or inert linkers using a combined experimental and modeling approach. These findings and the modeling framework might inform future studies for redox-responsive prodrug design and drug delivery systems.

Application of Microsponge Drug Platform to Enhance Methotrexate Administration in Rheumatoid Arthritis Therapy.

This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation and damage, while MTX is a common disease-modifying antirheumatic drug (DMARD), the conventional use of which is limited by adverse effects and the lack of release control. MSP were synthesized as freeze-dried powder to increase their stability and allow for a facile reconstitution prior to administration and precise MTX dosing. A highly stable and rounded-shaped micrometric MSP, characterized by an open porosity inner structure, achieved both a high MTX loading efficiency and a slow release of MTX after injection. Our drug release assays indeed demonstrated a characteristic drug release profile consisting of a very limited burst release in the first few hours, followed by a slow release of MTX sustained for over a month. By means of a preclinical rat model of RA, the administration of MTX-loaded MSP proved to nearly double the therapeutic efficacy compared to sole MTX, according to a steep reduction in arthritic score compared to control groups. The preclinical study was replicated twice to confirm this improvement in performance and the safety profile of the MSP. This study suggests that the MSP drug delivery platform holds significant potential for clinical use in improving RA therapy by enabling the sustained slow release of MTX, thereby enhancing therapeutic outcomes and minimizing side effects associated with conventional burst-release drug administration.

Polydopamine Decorated Hyaluronic Acid Clusters for Tumor Cell Targeting Combination Therapy via Template Self-Consumption Methods.

Photothermal-chemodynamic-chemotherapy (PTT-CDT-CT) combination therapy significantly enhances the therapeutic efficacy against tumors. However, synthesizing PTT-CDT-CT nanosystems is complex, typically requiring the preparation and conjugation of three components into a single carrier. To overcome this challenge, a facile template self-consumption method is developed. In this approach, hyaluronic acid (HA), recognized for its tumor cell targeting properties, chelates with Cu2+ to form Cu-HA, which then transforms into CuO2@HA cluster templates. These templates self-consume gradually, producing ·OH and Cu2+, which catalyze the rapid polymerization of dopamine and coordinate with polydopamine respectively, enhancing the photothermal conversion efficiency. After gossypol loading, GPDA@HA clusters are formed, achieving high gossypol loading efficiency due to π-π stacking between gossypol and PDA, as well as coordination between gossypol and Cu2+. The GPDA@HA clusters are effectively internalized by tumor cells through endocytosis, mediating the synergistic damage or inhibition of intracellular proteins, and nucleic acids against tumor cells via PTT, CDT, and CT. Crucially, the synergism of PTT-CDT-CT combination therapy far surpasses those of a single modality. This work introduces a new pathway for the synthesis of PTT-CDT-CT nanosystems, avoiding the conventional synthesis and loading of different therapeutic agents, and provides insights into developing personalized drug combination therapies with high efficacy.

Nanocarriers Made of Natural Fatty Acids: Modulation of Their Release Profiles through Photo-Crosslinking.

Natural fatty acids are attractive carrier materials for drug delivery, but their rapid dissolution and degradation in vivo calls for new strategies to enhance their stability. Here we report a simple and versatile method capable of photo-crosslinking carriers made of natural fatty acids for drug delivery under controlled release. By optimizing the crosslinking density, the nanoscale carriers show a high drug loading efficiency, together with a stable network structure for minimal degradation in a body fluid mimic. Fluorescence microscopy analysis also reveals the exceptional intracellular stability of the crosslinked network, resulting in negligible cytotoxicity toward A549 cells up to 24 h when loaded with a potent anticancer drug. We further extend this strategy to microscale carriers fabricated using electrospray. Upon photo-crosslinking, the carriers show a retarded release of nerve growth factor, resulting in slower neurite outgrowth from dorsal root ganglion. This work holds promise for addressing the efficacy and safety issues critical to nanomedicine and related applications.

Nanocarriers Made of Natural Fatty Acids: Modulation of Their Release Profiles through Photo‐Crosslinking

AbstractNatural fatty acids are attractive carrier materials for drug delivery, but their rapid dissolution and degradation in vivo calls for new strategies to enhance their stability. Here we report a simple and versatile method capable of photo‐crosslinking carriers made of natural fatty acids for drug delivery under controlled release. By optimizing the crosslinking density, the nanoscale carriers show a high drug loading efficiency, together with a stable network structure for minimal degradation in a body fluid mimic. Fluorescence microscopy analysis also reveals the exceptional intracellular stability of the crosslinked network, resulting in negligible cytotoxicity toward A549 cells up to 24 h when loaded with a potent anticancer drug. We further extend this strategy to microscale carriers fabricated using electrospray. Upon photo‐crosslinking, the carriers show a retarded release of nerve growth factor, resulting in slower neurite outgrowth from dorsal root ganglion. This work holds promise for addressing the efficacy and safety issues critical to nanomedicine and related applications.

Novel double-layered PLGA microparticles-dissolving microneedle (MPs-DMN) system for peptide drugs sustained release by transdermal delivery.

The combination of microparticles (MPs) with dissolving microneedles (DMN) represents a promising transdermal approach for the sustained release of biomacromolecule drug. In this study, we developed a double-layered microparticles-dissolving microneedle (MPs-DMN) system, which strategically concentrates PLGA MPs at the tip of the microneedle to achieve sustained release of peptide drugs through transdermal delivery. We selected exenatide (EXT) as a model peptide drug and established HPLC-UV and UPLC-MS methods for the quantitative analysis of the drug content of MPs-DMN and drug concentrations in plasma. Ultrasonication was utilized in the first step of the double emulsion solvent evaporation method to produce PLGA microparticles, achieving a high drug loading efficiency of 22.76 ± 0.64 %, surpassing the commercial products. The EXT-loaded microparticles were then mixed with 10 % w/v sucrose solution to form the first layer of the microneedle, and the mixture of the base solution was added to form the double-layered dissolving microneedle. Microscopic analysis revealed that the MPs were predominantly concentrated in the upper 50 % of the microneedle body, resulting in an impressive drug delivery efficiency of 92.86 ± 1.62 %. The MPs-DMN patch demonstrated the capability to 238.20 ± 5.79 μg of EXT within a compact area of 0.75 cm2, surpassing the capacities reported in existing research. The insertion and dissolution assessments exhibited rapid dissolution, maintaining the MPs as an effective drug reservoir within the skin. Pharmacokinetic assessments indicated that the long half-life (T1/2) of 466.4 ± 12.2 h and high relative bioavailability of 89.71 % for MPs-DMN. Furthermore, pharmacodynamic studies indicated that the MPs-DMN effectively controlled blood glucose levels below 20 mmol/L in diabetic (db/db) mouse for two weeks. These promising findings suggest that the MPs-DMN system could serve as a viable transdermal delivery method for the prolonged administration of peptide drugs.

A physical crosslinked pH-sensitive hydrogel based on hemicellulose/graphene oxide for controlled oral drug delivery.

The design of innovative pH-sensitive hydrogels for oral drug delivery is particularly promising for the treatment of intestinal diseases. The traditional pH-responsive hydrogels still have some problems such as low biocompatibility, complex preparation process and poor therapeutic effect, so a new method needs to be developed to solve these problems. Here, a pH-sensitive hemicellulose/graphene oxide (HC/GO) composite hydrogel (HGCH) was prepared through a one-step strategy. Benefitting from the multiple hydrogen bonding between HC and GO, HGCH possessed a low gelator concentration (∼0.79wt%), well-defined 3D porous network and excellent mechanical properties. Remarkably, HGCH exhibited pH-induced gel-sol transition and a high drug loading efficiency, showing great potential as a candidate for advanced drug carrier. The drug loading and release test revealed that about 85% Vitamin B 12 was released in neutral PBS solution (pH7.4). However, only about 30% drug was diffused into acid medium (pH1.7) in the same period, which suggested the HGCH have high adaptability to soluble drugs and pH sensitivity triggered release. Further cellular toxicity tests demonstrated that the HGCH was nontoxic and biocompatible for cells. Thus, the physically cross-linked HGCH would be an attractive drug carrier for controlled drug release at physiological pH in the future.

Fabrication of a 2D-Surfactant Exfoliated Hexagonal Boron Nitride Nanoparticles as Efficient pH-Sensitive Drug Delivery System for Lung Cancer Therapy

Lung cancer is one of the most prevalent cancers and it is also the primary cause of cancer-related mortality globally. However, due to variations in tobacco use patterns, exposure to environmental risk factors, and genetics, lung cancer incidence and mortality rates vary significantly worldwide. Since smoking is the primary risk factor for lung cancer, developing more effective therapeutic strategies and innovative drug delivery systems may help to raise the disease's survival rates. In this study, a novel pH-sensitive nanocarrier based on a composite of a two-dimensional hexagonal boron nitride (2D-hBN) with unique properties was synthesized to deliver Doxorubicin (DOX). Firstly, bulk hBN powder was exfoliated with a sodium cholate salt, sonicated, and centrifuged to obtain the as-prepared 2D-hBN nanocarriers, and finally, DOX was entrapped for targeted drug delivery and tumor therapy. High DOX loading and entrapment efficiency (LE% and EE%, respectively) were obtained. The EE% and LE% for sodium cholate exfoliated 2D-hBN obtained were 84.50% and 25.48%, respectively. In vitro drug release experiments demonstrated a pH-sensitive non-Fickian release profile with a release percentage of 73.5%. Preliminary in-vitro cytotoxicity was done via MTT assay, using the human lung adenocarcinoma cell line (A549), and the 2D-hBN@DOX nanocomposites were shown to drastically reduce the viability of the cancer cells compared to 2D-hBN, indicating the great efficacy of the former nanocomposites in hindering the proliferation of cancer cells.

Designing of amiloride loaded citrate functionalized amorphous silica nanoparticles to investigate its genotoxic and cytotoxic potential

In the present work, silica-based nanocarrier for the anticancer drug, amiloride have been synthesized and characterized using various physicochemical techniques. The aim of this work emphasis on investigating the physicochemical properties and cytotoxic effects of citrate-functionalized amiloride loaded silica nanoparticles. Silica nanoparticles synthesis was carried out via condensation reaction, then coated by tris sodium citrate, followed by their functionalization using amiloride through EDC-NHS reaction. SEM and HR-XRD analysis indicated the formation of amorphous spherical silica nanoparticles. The existence of citrate coating was evident from FT-IR and TGA results, which were supported by DLS and zeta potential studies. The formation of amiloride conjugated citrate coated silica nanoparticles (SiNPs-Cit@Ami) was confirmed by the DLS, Zeta potential and UV-Visible spectroscopy. Size of SiNPs-Cit@Ami nanoparticles was found to be around 80nm using TEM. Additionally, these nanoparticles showed high loading efficiency and time-dependent release of amiloride. DNA binding studies were examined using UV–Visible, Fluorescence spectroscopic and Competitive fluorescence studies. The results indicate that SiNPs-Cit@Ami bind to Ct-DNA via minor groove binding mode. Furthermore, the cytotoxic effect of SiNPs-Cit@Ami on HepG2 cell lines was found to be higher than amiloride alone. Our findings suggest that SiNPs-Cit@Ami can be employed as a promising candidate for cancer mitigation.

Supramolecular Assembly‐Enabled Transdermal Therapy of Hypertrophic Scarring Through Concurrent Ferroptosis‐Apoptosis

AbstractHypertrophic scar (HS) remains a major challenge for clinicians due to unsatisfactory therapeutic performance. Although inducing apoptosis of HS fibroblasts (HSFs) has proved to be an effective nonsurgical treatment strategy, potential chemotherapy resistance to apoptosis of HSFs makes the development of new and efficient strategies highly demanding. Herein, a ferroptosis‐apoptosis combined therapeutic strategy for the treatment of HS is developed through supramolecular self‐assembly between cucurbit[7]uril (CB[7]) and two bioactive agents, dihydroartemisinin (DHA) and gold nanoclusters (AuNCs). The resulting self‐assembled supramolecular nanoparticles, named CAD NPs, showed high guest loading efficiency and prominent pH‐responsive degradability in the acidic lysosomes of HSFs. Importantly, both DHA and AuNCs act synergistically to generate excessive reactive oxygen species and lipid peroxidation, leading to mitochondrial damage, and ultimately inducing concurrent ferroptosis and apoptosis on HSFs. Upon further loading into hydrogel microneedles to facilitate their transdermal delivery, these CAD NPs showed superior antiscar therapeutic effects in shortening the treatment span to 3 weeks and improving the HS appearance, as demonstrated at a rabbit ear model of HS. The present supramolecular assembly‐based ferroptosis‐apoptosis strategy provides an innovative guideline for efficiently treating HS as well as other diseases.

Discharge Characteristics of High-Loading Coated Cathode Active Materials for High-Capacity High-Efficiency Secondary Batteries Implementation

In response to the demand for secondary batteries, mass production of secondary battery materials is required, leading to the need for significantly increased production capacity and the development of high-speed production systems for electrode materials. Furthermore, in accordance with global environmental regulations and energy management regulations, reducing carbon emissions is necessary for enhancing future competitiveness through the application of eco-friendly and digital processes. Additionally, to meet the demands of commercializing high-energy-density secondary batteries and achieving carbon neutrality, it is necessary to establish advanced and efficient electrode manufacturing systems. Therefore, the design and development of processes for dispersing components that determine the physical properties of slurries, as well as mixing and coating processes for battery manufacturing, are crucial. Density control ensures accurate material composition, and control of component ratios and viscosity is essential for ensuring consistency in slurry manufacturing processes. During discharge, as the active material at the cathode undergoes reduction, the energy difference with the reference electrode gradually decreases, resulting in a decrease in cell potential. The slope change of the discharge curve is influenced by factors such as the extent of lithium ion diffusion at the surface of the active material particles, phase transitions of the active material, collapse of crystal structure, and leaching of transition metal ions comprising the active material into the electrolyte. Moreover, even at the same current density, charge and discharge curves may vary depending on factors such as particle size and size distribution of the active material, temperature, mixing conditions of active material/binder/conductive agent, electrolyte characteristics, and porous structure of the separator. In this study, the evaluation of electrode characteristics of active materials was conducted to optimize coating conditions and mixing conditions for achieving high efficiency and high loading for the implementation of high-energy-density secondary batteries. Through evaluation based on C-rate according to Loading Level, analysis of capacity implementation characteristics based on electrode density was performed, aiming to apply it to the development of carbon reduction-type high-loading, wide-electrode slurry coating equipment systems for the implementation of high-energy-density secondary batteries. Expectations include the development of carbon reduction process technologies through maximum homogeneity, enhancing production speed, and energy savings in processes.Secondary battery, Cathode active material, Slurry, Loading level, C-rateThis work was supported by the Technology Innovation Program (RS-2022-00155881, Development of high-efficiency and high-loading coating system for implementation of 350Wh/kg secondary battery) funded By the Ministry of Trade, Industry & Energy(MOTIE, Korea)