Unlocking the Power of Human Ferritin: Enhanced Drug Delivery of Aurothiomalate in A2780 Ovarian Cancer Cells.

Aurothiomalate (AuTM) is an FDA-approved antiarthritic gold drug with unique anticancer properties. To enhance its anticancer activity, we prepared a bioconjugate with human apoferritin (HuHf) by attaching some AuTM moieties to surface protein residues. The reaction of apoferritin with excess AuTM yielded a single adduct, that was characterized by ESI MS and ICP-OES analysis, using three mutant ferritins and trypsinization experiments. The adduct contains ~3 gold atoms per ferritin subunit, arranged in a small cluster bound to Cys90 and Cys102. MD simulations provide a plausible structural model for the cluster. The adduct was evaluated for its pharmacological properties and was found to be significantly more cytotoxic than free AuTM against A2780 cancer cells mainly due to higher gold uptake. NMR-metabolomics showed that AuTM bound to HuHf and free AuTM induced qualitatively similar changes in treated cancer cells, indicating that the effects on cell metabolism are approximately the same, in agreement with independent biochemical experiments. In conclusion, we have demonstrated here that a molecularly precise bioconjugate formed between AuTM and HuHf exhibits anticancer properties far superior to the free drug, while retaining its key mechanistic features. Evidence is provided that human ferritin can serve as an excellent carrier for this metallodrug.

Epilepsy Treatment and Diagnosis Enhanced by Current Nanomaterial Innovations: A Comprehensive Review.

Epilepsy is a complex disease in the brain. Complete control of seizure has always been a challenge in epilepsy treatment. Currently, clinical management primarily involves pharmacological and surgical interventions, with the former being the preferred approach. However, antiepileptic drugs often exhibit low bioavailability due to inherent limitations such as poor water solubility and difficulty penetrating the blood-brain barrier (BBB). These issues significantly reduce the drugs' effectiveness and limit their clinical application in epilepsy treatment. Additionally, the diagnostic accuracy of current imaging techniques and electroencephalography (EEG) for epilepsy is suboptimal, often failing to precisely localize epileptogenic tissues. Accurate diagnosis is critical for the surgical management of epilepsy. Thus, there is a pressing need to enhance both the therapeutic outcomes of epilepsy medications and the diagnostic precision of the condition. In recent years, the advancement of nanotechnology in the biomedical sector has led to the development of nanomaterials as drug carriers. These materials are designed to improve drug bioavailability and targeting by leveraging their large specific surface area, facile surface modification, ability to cross the BBB, and high biocompatibility. Furthermore, nanomaterials have been utilized as contrast agents in imaging and as materials for EEG electrodes, enhancing the accuracy of epilepsy diagnoses. This review provides a comprehensive examination of current research on nanomaterials in the treatment and diagnosis of epilepsy, offering new strategies and directions for future investigation.

Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

Evaluating dasatinib nanocarrier: Physicochemical properties and cytotoxicity activity on cancer cells.

Objective: Dasatinib-(DAS) is a tyrosine kinase inhibitor usually used to treat leukemia. However, DAS is a poorly water-soluble drug. Therefore, oil-in-water emulsions were used for DAS to enhance its solubility and cancer treatment efficacy. This study aims to develop an appropriate DAS nanoemulsion (NE) that can overcome the issue of DAS solubility and provide an effective anticancer effect. Methods: Spherical particles dispersed in an aqueous media approach within an oily phase (oleic acid, Kolliphor RH40, and dipropylene glycol) were used to formulate DAS-NE using high-energy methods. Different formulas were developed and an appropriate formula was analyzed to identify its physicochemical properties. Raw DAS and nonformula cytotoxicity were evaluated through MTT assay against three cancer cell lines, MCF7 (human breast adenocarcinoma), HT29, and SW480 (human colorectal carcinomas), in addition to MRC5 (Normal human fetal lung fibroblast). Results: Different DAS-NEs (1-7) have been developed successfully. Formulas had a droplet size of a diameter ranging from 84.167 ± 10.178 nm to 273.433 ± 45.267 nm. The drug content of the appropriate formula (DAS-NE3) was found to be 83.2%. The drug release result of DAS-NE3 when compared to raw DAS was about 58%, falling to 13% after 24 h. The DAS-NE3 showed cytotoxicity against the three cancer cells below 26.11 µM but showed 30-fold significantly increased selectivity against MRC5 normal cells compared to that of raw DAS. Conclusion: This study shows that the DAS-NE3 formula may provide a potentially effective and sustained drug delivery for cancer treatment. This provides valuable information to the scientific community and the pharmaceutical industry.

Poly (hydroxyethylmethacrylate-co-methacryloyl glutamic acid) nanocarrier system for controlled release of levothyroxine.

The deterioration in the structure of thyroid hormones causes many thyroid-related disorders, which leads to a negative effect on the quality of life, as well as the change in metabolic rate. For the treatment of thyroid disorders, daily use of levothyroxine-based medication is essential. In the study, it is aimed to develop a polymeric nanocarrier that can provide controlled drug release of levothyroxine. In this respect, the p(HEMA-MAGA) nanopolymer was synthesized and then characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis. The specific surface area of the nanopolymer was calculated as 587.68 m2/g. The pH, temperature, concentration, and time parameters were determined for levothyroxine binding to p(HEMA-MAGA) and optimum binding was determined as pH 7.4, 25 °C, 25 µg/mL concentration, and 30 min adsorption time. As a result of the release performed at pH 7.4, a release profile was observed which increased for the first 3 days and continued for 14 days. According to the results of MTT cell viability analysis, it was determined that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect. This developed polymer-based nanocarrier system is suitable for long-term and controlled release of levothyroxine. This is a unique and novel study in terms of developing poly hydroxyethylmethacrylate-co-methacryloyl glutamic acid-based polymeric nanoparticles for levothyroxine release.

Affinity-based nanoparticles were developed for long-term and controlled release of levothyroxine.p(HEMA-MAGA) nanopolymer was synthesized and characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Zeta size analysis.Optimization studies of levothyroxine binding into p(HEMA-MAGA) nanopolymers were carried out and controlled release studies were made with loading in optimum parameters.MTT cell viability analysis were performed for determining that the p(HEMA-MAGA) nanopolymeric carrier system had no cytotoxic effect.

A Patent Analysis on Nano Drug Delivery Systems.

BACKGROUND: A nano drug delivery system is an effective tool for drug delivery and controlled release, which is used for a variety of medical applications. In recent decades, nano drug delivery systems have been significantly developed with the emergence of new nanomaterials and nanotechnologies. OBJECTIVE: This article aimed to provide insight into the technological development of nano drug delivery systems through patent analysis. METHODS: 3708 patent documents were used for patent analysis after retrieval from the Incopat patent database. RESULTS: The number of patents on nano drug delivery systems has shown a rapid growth trend in the past two decades. At present, China and the United States have obvious contributions to the number of patents. According to the patent data, the nanomaterials used in nano drug delivery system are mainly inorganic nanomaterials, lipid-based nanomaterials, and macromolecules. In recent years, the highly cited patents (≥14) for nano drug delivery systems mainly involve lipid-based nanomaterials, indicating that their technology is mature and widely used. The inorganic nanomaterials in drug delivery have received increasing attention, and the number of related patents has increased significantly after 2016. The number of highly cited patents in the United States is 250, which is much higher than in other countries. CONCLUSION: Even after decades of development, nano drug delivery systems remain a hot topic for researchers. The significant increase in patents since 2016 can be attributed to the large number of new patents from China. However, according to the proportion of highly cited patents in total, China's patented technologies in nano drug delivery systems are not advanced enough compared to developed countries, including the United States, Canada, Germany, and France. In the future, research on emerging nanomaterials for nano drug delivery systems, such as inorganic nanomaterials, may focus on developing new materials and optimising their properties. The lipid-based and polymer- based nanomaterials can be continuously improved for the development of new nanomedicines.

Enhanced Stability of α-Mangostin-Rich Extract and Selective Cytotoxicity against Cancer Cells via Encapsulation in Antioxidant Nanoparticles (AME@NanoAOX).

α-Mangostin-rich extract (AME) shows promise as a functional ingredient for cancer chemotherapy. Here, we encapsulated AME in our originally designed antioxidant nanoparticles (NanoAOX) to increase its solubility and prevent oxidative degradation (AME@NanoAOX). In this study, two types of self-assembled polymers containing nitroxide radicals were engineered. These polymers were self-assembled into nanoscale particles in aqueous media, entrapping AME (abbreviated as AME@NanoAOX(B) and AME@NanoAOX(G)). These formulations considerably improved the stability of AME against oxidative degradation and exhibited different release profiles of α-mangostin under different pH conditions. Furthermore, AME-encapsulated nanoparticles exhibited potent cytotoxicity against various cancer cell lines, including human breast cancer (MCF-7), human lung cancer (A549), human colon cancer (Caco-2), human cervical cancer (HeLa), and human liver cancer (HepG2) cell lines, with minimal cytotoxicity in normal human mammary epithelial cells (hTERT-HME1), thus providing a high selectivity index (SI). These results indicated the promising feature of AME-encapsulated antioxidant nanoparticles (AME@NanoAOX) for cancer chemotherapy.

Polymeric nanocarriers delivery systems in ischemic stroke for targeted therapeutic strategies.

Ischemic stroke is a complex, high-mortality disease with multifactorial etiology and pathogenesis. Currently, drug therapy is mainly used treat ischemic stroke in clinic, but there are still some limitations, such as limited blood-brain barrier (BBB) penetration efficiency, a narrow treatment time window and drug side effects. Recent studies have pointed out that drug delivery systems based on polymeric nanocarriers can effectively improve the insufficient treatment for ischemic stroke. They can provide neuronal protection by extending the plasma half-life of drugs, enhancing the drug's permeability to penetrate the BBB, and targeting specific structures and cells. In this review, we classified polymeric nanocarriers used for delivering ischemic stroke drugs and introduced their preparation methods. We also evaluated the feasibility and effectiveness and discussed the existing limitations and prospects of polymeric nanocarriers for ischemic stroke treatment. We hoped that this review could provide a theoretical basis for the future development of nanomedicine delivery systems for the treatment of ischemic stroke.

Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment. / çº³ç±³å¡ä»‹è‹—æ”¹å–„è†€èƒ±ç™Œçš„å ç–«æ²»ç–—æ•ˆæžœ.

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment. / çº³ç±³å¡ä»‹è‹—æ”¹å–„è†€èƒ±ç™Œçš„å ç–«æ²»ç–—æ•ˆæžœ.

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

Synthetic genomic nanomedicine with triple-responsiveness for systemic anti-tumor therapy.

To overcome the biological barriers in the journey of systemic gene delivery, a multifaceted genomic synthetic nanomedicine was elaborated and strategically equipped with a multiple of intriguing responsiveness. Particularly, core-shell plasmid DNA condensates were created based on polyionic complexation with block copolymer of polyethylene glycol (PEG)-polylysine (PLys), namely, the nanoscaled PLys&pDNA nanoparticle tethered with the biocompatible PEG surroundings. Furthermore, redox-reversible disulfide crosslinking was introduced into PLys&pDNA nanoparticle to accomplish adequate structural stabilities, and thermal-responsive polypropylacrylamide (PNIPAM) was introduced as the secondary intermediate surroundings onto the pre-formulated PLys&pDNA nanoparticle with the aim of preventing the potential enzymatic degradation from the environmental nucleases. Hence, hundreds of times prolonged survival and retention was determined in pertinent to the blood circulation properties. Additionally, the installation of a guide ligand at the distal end of PEG segments was proposed to encourage selective tumor uptake. A linear peptide of GPLGVRG, which is selectively susceptible to digestion by the tumor-enriched matrix metalloproteinase 2 (MMP-2), was used as the linkage between the shell and core. This peptide has been shown to detach the bio-inert PEGylation, resulting in further facilitated cell endocytosis and intracellular trafficking activities. Hence, the precisely defined synthetic nanomedicine, which exhibits desirable characteristics, efficient expression of the therapeutic gene in the affected cells, and contributed to potent therapeutic efficacy in systemic treatment of intractable tumors by encapsulating the anti-angiogenic gene.

On the Structure, Stability, and Cell Uptake of Nanostructured Lipid Carriers for Drug Delivery.

The efficacy of nanostructured lipid carriers (NLC) for drug delivery strongly depends on their stability and cell uptake. Both properties are governed by their compositions and internal structure. To test the effect of the lipid composition of NLC on cell uptake and stability, three kinds of liquid lipids with different degrees of unsaturation are employed. After ensuring homogeneous size distributions, the thermodynamic characteristics, stability, and mixing properties of NLC are characterized. Then the rates and predominant pathways of cell uptake are determined. Although the same surfactant is used in all cases, different uptake rates are observed. This finding contradicts the view that the surface properties of NLC are dominated by the surfactant. Instead, the uptake rates are explained by the structure of the nanocarrier. Depending on the mixing properties, some liquid lipids remain inside the nanocarrier, while other liquid lipids are present on the surface. Nanocarriers with liquid lipids on the surface are taken up more readily by the cells. This shows that the engineering of efficient lipid nanocarriers requires a delicate balance of interactions between all components of the nanocarrier on the molecular level.

Camptothecin-loaded mesoporous silica nanoparticles functionalized with CpG oligodeoxynucleotide as a new approach for skin cancer treatment.

The therapeutic efficacy of camptothecin (CPT), a potent antitumor alkaloid, is hindered by its hydrophobic nature and instability, limiting its clinical use in treating cutaneous squamous cell carcinoma (SCC). This study introduces a novel nano drug delivery system (NDDS) utilizing functionalized mesoporous silica nanoparticles (FMSNs) for efficient CPT delivery. The FMSNs were loaded with CPT and subsequently coated with chitosan (CS) for enhanced stability and bioadhesion. Importantly, CpG oligodeoxynucleotide (CpG ODN) was attached onto the CS-coated FMSNs to leverage the immunostimulatory properties of CpG ODN, augmenting the chemotherapy's efficacy. The final formulation FMSN-CPT-CS-CpG displayed an average size of 241 nm and PDI of 0.316 with an encapsulation efficiency of 95 %. Comprehensive in vitro and in vivo analyses, including B16F10 cells and DMBA/TPA-induced SCC murine model, demonstrated that the FMSN-CPT-CS-CpG formulation significantly enhanced cytotoxicity against B16F10 cells and induced complete regression in 40 % of the in vivo subjects, surpassing the efficacy of standard CPT and FMSN-CPT treatments. This study highlights the potential of combining chemotherapeutic and immunotherapeutic agents in an NDDS for targeted, efficient skin cancer treatment.

The chitinase genes TuCht4 and TuCht10 are indispensable for molting and survival of Tetranychus urticae.

Insect chitinases (Chts) play a crucial role in the molting process, enabling continuous growth through sequential developmental stages. Based on their high homology to insect Chts, TuCht1 (group II), TuCht4 (group I) and TuCht10 (group IV) were identified, and their roles during molting process were investigated. TuCht1 was mainly expressed in the deutonymphal stage, while TuCht4 was mainly expressed in the nymphal stage and the highest expression level of TuCht10 was observed in the larvae. Feeding RNAi assays have shown that group I TuCht4 and group Ⅳ TuCht10 are involved in mite molting. Suppression of TuCht4 or TuCht10 resulted in high mortality, molting abnormalities and the absence of distinct electron dense layers of chitinous horizontal laminae in the cuticle, as demonstrated by scanning electron microscopy and transmission electron microscopy. The nanocarrier mediated RNAi had significantly higher RNAi efficiency and caused higher mortality. The results of the present study suggest that chitinase genes TuCht4 and TuCht10 are potential targets for dietary RNAi, and demonstrates a nanocarrier-mediated delivery system to enhance the bioactivity of dsRNA, providing a potential technology for green pest management.

Theoretical investigations on modeling blood flow through vessel for understanding effectiveness of magnetic nanocarrier drug delivery systems.

For cancer therapy, the focus is now on targeting the chemotherapy drugs to cancer cells without damaging other normal cells. The new materials based on bio-compatible magnetic carriers would be useful for targeted cancer therapy, however understanding their effectiveness should be done. This paper presents a comprehensive analysis of a dataset containing variables x(m), y(m), and U(m/s), where U represents velocity of blood through vessel containing ferrofluid. The effect of external magnetic field on the fluid flow is investigated using a hybrid modeling. The primary aim of this research endeavor was to construct precise and dependable predictive models for velocity, utilizing the provided input variables. Several base models, including K-nearest neighbors (KNN), decision tree (DT), and multilayer perceptron (MLP), were trained and evaluated. Additionally, an ensemble model called AdaBoost was implemented to further enhance the predictive performance. The hyper-parameter optimization technique, specifically the BAT optimization algorithm, was employed to fine-tune the models. The results obtained from the experiments demonstrated the effectiveness of the proposed approach. The combination of the AdaBoost algorithm and the decision tree model yielded a highly impressive score of 0.99783 in terms of R2, indicating a strong predictive performance. Additionally, the model exhibited a low error rate, as evidenced by the root mean square error (RMSE) of 5.2893 × 10-3. Similarly, the AdaBoost-KNN model exhibited a high score of 0.98524 using R2 metric, with an RMSE of 1.3291 × 10-2. Furthermore, the AdaBoost-MLP model obtained a satisfactory R2 score of 0.99603, accompanied by an RMSE of 7.1369 × 10-3.

C176-loaded and phosphatidylserine-modified nanoparticles treat retinal neovascularization by promoting M2 macrophage polarization.

Retinal neovascularization (RNV), a typical pathological manifestation involved in most neovascular diseases, causes retinal detachment, vision loss, and ultimately irreversible blindness. Repeated intravitreal injections of anti-VEGF drugs were developed against RNV, with limitations of incomplete responses and adverse effects. Therefore, a new treatment with a better curative effect and more prolonged dosage is demanding. Here, we induced macrophage polarization to anti-inflammatory M2 phenotype by inhibiting cGAS-STING signaling with an antagonist C176, appreciating the role of cGAS-STING signaling in the retina in pro-inflammatory M1 polarization. C176-loaded and phosphatidylserine-modified dendritic mesoporous silica nanoparticles were constructed and examined by a single intravitreal injection. The biosafe nanoparticles were phagocytosed by retinal macrophages through a phosphatidylserine-mediated "eat me" signal, which persistently release C176 to suppress STING signaling and thereby promote macrophage M2 polarization specifically. A single dosage can effectively alleviate pathological angiogenesis phenotypes in murine oxygen-induced retinopathy models. In conclusion, these C176-loaded nanoparticles with enhanced cell uptake and long-lasting STING inhibition effects might serve as a promising way for treating RNV.

Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retina-derived RPE cell line.

AIM: To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line. METHODS: Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of VEGF-A and PDGF-A, PDGF-B, PDGF-C, PDGF-D genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR). RESULTS: The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC50) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D after treatment with both free and niosomal AUR. CONCLUSION: Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

The smart nanocarrier containing zein/starch co-biopolymers enhanced by graphitic carbon nitride; exploring opportunities in brain cancer treatment.

In this investigation, we present an innovative pH-responsive nanocomposite designed to address challenges associated with using 5-Fluorouracil (5-FU) in cancer therapy. The nanocomposite containing zein (Z), starch (S), and graphitic carbon nitride (g-C3N4) macromolecules is synthesized by a water-in-oil-in-water (W/O/W) double emulsion technique, serving as a carrier for 5-FU. The S/Z hydrogel matrix's entrapment and loading efficiency are greatly improved by adding g-C3N4 nanosheets, reaching noteworthy values of 45.25 % and 86.5 %, respectively, for drug loading efficiency and entrapment efficiency. Characterization through FTIR and XRD validates the successful loading of 5-FU, elucidating the chemical bonding within the nanocomposite and crystalline characteristics. Structural analysis using FESEM, along with DLS and zeta potential measurements, reveals an average nanocomposite size of 193.48 nm, indicating a controlled structure, and a zeta potential of -42.32 mV, signifying a negatively charged surface. Studies on the in vitro release of drugs reveal that 5-FU is delivered more effectively and sustainably in acidic environments than in physiological circumstances. This highlights the fact that the created nanocarrier is pH-sensitive. Modeling release kinetics involves finding the right mathematical conditions representing underlying physicochemical processes. Employing curve-fitting techniques, predominant release mechanisms are identified, and optimal-fitting kinetic models are determined. The Baker kinetic model performed best at pH 7.4, indicating that the leading cause of the drug release was polymer swelling. In contrast, the Higuchi model was most accurate for drug release at pH 5.4, illuminating the diffusion and dissolution mechanisms involved in diffusion. To be more precise, the mechanism of release at pH 7.4 and 5.4 was anomalous transport (dissolution-controlled), according to the Korsmeyer-Peppas mathematical model. The pH-dependent swelling and degradation behavior of S/Z/g-C3N4@5-FU nanocomposite showed higher swelling and faster degradation in acidic environments compared to neutral conditions. Crucially, outcomes from the MTT test affirm the significant cytotoxicity of the 5-FU-loaded nanocomposite against U-87 MG brain cancer cells, while simultaneously indicating non-toxicity towards L929 fibroblast cells. These cumulative findings underscore the potential of the engineered S/Z/g-C3N4@5-FU as a productive and targeted therapeutic approach for cancer cells.

An Insight into Cubosomal Drug Delivery Approaches: An Explicative Review.

Cubosomes, a novel drug delivery system, have gained significant attention in recent years due to their unique self-assembled structures and enhanced drug encapsulation capabilities. They are administered by oral, ophthalmic, transdermal, and chemotherapeutic routes, to name a few. Due to their many potential benefits-which include high drug dispersal due to the cubic structure, a large surface area, a relatively simple manufacturing process, biodegradability, the capacity to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and the biodegradability of lipids-cubosomes show enormous promise in drug nanoformulations for cancer therapeutics. The most common preparation method involves emulsifying a monoglyceride with a polymer, homogenizing, and then sonicating the mixture. Two distinct approaches to preparing are top-down and bottom-up. This evaluation will examine the materials, methods of preparation, cubosome-related drug encapsulating techniques, drug loading, release mechanism, and their uses. The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents (2015-2024), the keywords "cubosome; drug delivery systems, nano-carrier, theranostic, drug release mechanism" and others of a similar nature were utilized. This review will conduct a comprehensive analysis of the cubosome-related composition, production methods, drug encapsulating strategies, drug release mechanisms, and applications. Moreover, the difficulties encountered in fine-tuning different parameters to improve loading capabilities and prospects are also discussed. Innovation in pharmaceutical research and development can be stimulated by the knowledge gathered about cubosomal drug delivery methods. Through the clarification of the mechanisms involved in drug release from cubosomes and the investigation of innovative fabrication procedures, scientists can enhance the cubosomal formulation design for targeted therapeutic uses.