Colloids and Surfaces B: Biointerfaces最新文献

Albendazole (ABZ), an anthelmintic drug, has been repurposed to treat various types of cancers. However, poor solubility of ABZ, resulting in low bioavailability, limits its application. Nanosuspension is a versatile method for enhancing the dissolution of hydrophobic molecules, but a successful drying has been the biggest challenge in the field. The objective of this research is to formulate and optimize ABZ nanosuspension (NS) coated granules for rapid delivery of ABZ for the treatment of colorectal cancer. ABZ NS was prepared by dual centrifugation method using Kollidon® VA64 and sodium lauryl sulphate (SLS) as stabilizers. The processing method was optimized to obtain a stable nanosuspension with particle size < 300 nm. The optimized ABZ NS was coated on microcrystalline cellulose (MCC) to form the nano-coated granules (NCG) and filled in EUDRACAP® for colon targeted delivery. The ABZ NS and NCG achieved ∼ 60 % and ∼55 % drug release, respectively, in presence of bile salt at colonic pH. Half-maximal inhibitory concentration (IC₅₀) of ABZ NS was found to be 1.18 ± 0.081 µM and 3.59 ± 0.080 µM in two colorectal cancer cell lines: HCT 116 and HT-29, respectively. In addition, In vitro 3D tumor assay revealed that ABZ NS has superior tumor growth inhibition activity compared to the control and pure ABZ. The preparation of ABZ NCG in EUDRACAP® could be a promising approach to achieve colon targeted delivery and to repurpose ABZ for the treatment of colorectal cancer.

Zein, a maize protein, has been explored for constructing potential biomaterial due to its hydrophobic nature, self-assembly capability, and biocompatibility. In its nanoparticulate form, zein is a promising material for drug delivery applications, particularly in cancer treatment. Despite the importance of colloidal stability for effective drug delivery, systematic studies investigating the effect of various surface modifying agents (MAs) on the zein nanoparticles (ZNPs)-based formulations are limited. This study employs quality-by-design (QbD) approach to optimize curcumin-loaded ZNPs, enhancing colloidal stability, size, and drug-encapsulation efficiency using different MAs for potential cancer therapy. Gum arabic (GA) emerged as the optimal stabilizer, with GA-stabilized curcumin-loaded ZNPs (GA-Cur-ZNPs) achieving a particle size of 184.8 ± 2.85 nm, zeta potential of -23.4 ± 0.56 mV and 87.1 ±1.55 % drug encapsulation efficiency, along with excellent colloidal stability over two months. The optimal formulation also demonstrated sustained release of Cur over 72 h. GA-Cur-ZNPs demonstrated lower IC₅₀ values and higher anti-proliferative effects on three different cancer cell lines compared to the free drug, while also exhibiting superior intracellular uptake. With negligible toxicity to human dermal fibroblast cells, the optimized Cur-GA-ZNPs show promise for safe and effective killing of cancer cells.

Graphene quantum dots (GQDs) possess unique optical and biocompatible properties, making them suitable candidates for biomedical and pharmaceutical applications. This study reports the hydrothermal synthesis of pristine-GQD and doped variants: Nitrogen-GQD and Sulfur-GQD. The materials underwent thorough characterization techniques such as UV-vis, fluorescence, XRD, FE-TEM/SEM, EDX, and Raman spectroscopy. The particle sizes of these GQDs range from 2 to 5 nm. We conducted a comprehensive study through MTT assays to evaluate the potential cytotoxic effect of GQD and the doped variants. This study demonstrated their synergistic interactions with an anti-cancer drug, methotrexate (MTX), and also improvement of cytocompatibility in the presence of folic acid (FA). Systematic MD simulations revealed a compacting effect on the dynamic behavior of GQD and its variants in the presence of drugs. Fluorescence spectroscopy and computational modeling suggest non-intercalative surface interactions between GQDs and the drugs. The cytotoxic activity of pristine GQD on HeLa cervical cancer cells is higher than that of N-GQD and S-GQD. When treated with GQD-IC₅₀-MTX-IC₅₀, only 5.6 % of HeLa cells remained viable. The doped variants exhibited bio-compatibility when tested on normal HEK cell lines. Overall, this study emphasizes the potential of GQDs for targeted cancer therapy through an interdisciplinary approach involving material characterization, computational modeling, and biological assays.

Biological barriers in the gastrointestinal tract (GIT) prevent oral absorption of insoluble drugs. Recently, significant progress has been made in the development of various nanoparticles (NPs) designed to enhance the efficacy of oral drugs. However, the mechanism underlying the intracellular transport of NPs remains unclear, and there are still limitations to improving the oral bioavailability of drugs. This article reviews the challenges faced in the absorption of oral NPs, proposes strategies to overcome these barriers, and discusses the future prospects.

To improve the sensitivity, accuracy and specificity of the assay, a two-dimensional silver substrate with EF=5.85×10⁸ was first synthesized as a SERS substrate, on the surface of which DSP molecules were modified to form a DSP-antibody coupling through the activation of two N-hydroxy succinimide (NHS) esters to capture TNF-α. Subsequently, aptamerized silver-coated gold nanospheres (Au@TFMBA@Ag) were synthesized as Surface-Enhanced Raman Scattering (SERS) recognition probes. These probes were employed to create a sandwich structure for the quantitative detection of Tumor Necrosis Factor-alpha (TNF-α), utilizing the SERS signal intensity at 1374 cm^-1. Quantitative detection of TNF-α was successfully accomplished within the concentration range of 10^-4 to 10^-10 mg·mL^-1. Clinical serum samples were collected and subjected to testing. Significance analysis, conducted through the T-test (p < 0.0001), unequivocally showed the method's ability to differentiate between sera from normal individuals and those diagnosed with colon cancer.

Hepatocellular carcinoma (HCC) exhibits an immunosuppressive tumor microenvironment, leading to a low objective response rate when immune checkpoint inhibitors (ICIs) are utilized. The cGAS-STING pathway demonstrates a powerful immune stimulatory effect, nevertheless, activation of this pathway triggers an upregulation of PD-L1, which inhibits the anti-tumor function of immune cells. The present study discovered that knockdown of MEF2D by a siRNA in H22 cells decreases the expression of PD-L1. Subsequently, tLyp-1-modified liposomes were developed for the delivery of SN38 and MEF2D-siRNA. The outcomes indicated that the modification of tLyp-1 could enhance the uptake of liposomes by tumor cells. tLip/siMEF2D/SN38 liposomes can effectively knockdown the expression of MEF2D in HCC cells and reduce the expression of PD-L1 in vitro and in vivo, thereby enhancing proliferation inhibition and apoptosis induction, and effectively suppressing the growth of tumors. SN38 treatment elevated the expression of p-TBK1 and p-IRF3 in tumor tissue, signifying the activation of the cGAS-STING pathway and facilitating the maturation of dendritic cells in vitro and in vivo. At the same time, the co-delivery of MEF2D-siRNA reduced the expression of PD-L1, thereby decreasing the quantity of M2 macrophages and myeloid-derived suppressor cells (MDSCs) in tumors, increasing the number of CD4+ T cells within the tumor, and strengthening the anti-tumor immune efficacy. In conclusion, our results suggest that tLyP-1 modified, SN38- and MEF2D siRNA-loaded liposomes have the potential for the treatment of HCC and optimize the immunotherapy of HCC via STING activation.

Polyetheretherketone (PEEK) has been broadly used in orthopedic implant devices. Nevertheless, the bioinert tended to cause implant loosening and bacterial infection in orthopedic and trauma surgery. In this study, a drug-laden chitosan coating (CS) was constructed and deposited on the porous surface of PEEK (CG-SPEEK) internal fixation plate for multi-functionalization. The physical characterizations of CG-SPEEK were further investigated in the morphology, hydrophilicity, surface energy, roughness, drug release and mechanical properties. CG-SPEEK exhibited excellent antibacterial capabilities in both Staphylococcus aureus and Escherichia coli compared to other groups. Besides, BMSCs cells showed better biocompatibility and certain osteogenic activity on composite coating in vitro. Furthermore, CG-SPEEK promoted bone regeneration to some extent and express certain effect against infections in vivo study. Overall, combining personalized design and modification is an innovative strategy to realized functionalization, which may have a strong potential in clinical application.

Several anions present in the extracellular matrix (ECM) not only have significant physiological functions in ECM but also play an important role in regulating peptide-based self-assembly. Herein, we have employed a non-conventional approach to overcome the limitations of the positively charged Cardin-motif peptide that failed to self-assemble at physiological pH. We used a simple and elegant strategy by employing different anions such as HPO₄^2-, Cl^- and I^- to mask the overall surface charge of peptide. Interestingly, these anions were utilized to modulate the nanostructure formation and mechanical stiffness of peptide hydrogels owing to their differential interactions with water molecules according to the Hofmeister series. Interestingly, these anions induced hydrogels showed diverse cellular responses on two different cell lines, fibroblast and neuronal, indicating diverse application potential of the new scaffold. Thus, this study emphasizes the importance of anions to regulate the self-assembly of Cardin-motif peptide and this approach can be utilized in developing the ideal biomimetic model of ECM for futuristic applications.

Atherosclerosis is often accompanied by inflammation and oxidative stress. Excessive reactive oxygen species (ROS) can damage the vascular endothelium, leading to endothelial dysfunction and reduced nitric oxide (NO) bioavailability. Further accumulation of ROS contributes to vascular cell damage, lipid peroxidation, and extracellular matrix deposition. Thus, clearing excess ROS and reshaping the oxidative microenvironment is essential for treating atherosclerosis (AS). In this study, Ebselen, which mimics glutathione peroxidase and possesses redox capabilities, was successfully synthesized. Subsequently, a multifunctional coating was designed using a combination of Ebselen and poly (trimethylene carbonate) (PTMC), capable of protecting cells from ROS-induced damage, promoting vascular endothelialization, and exhibiting anti-proliferative properties. The Ebselen-loaded coating effectively scavenges free radicals (with an elimination rate of 89 %), catalytically releases NO (0.96 × 10⁻¹⁰ to 1.26 × 10⁻¹⁰ mol/cm²/min), and sustainably delivers Ebselen to the lesion site through a redox cycle. Notably, this coating shows excellent hemocompatibility and cytocompatibility. Subcutaneous implantation results indicated that the fibrous capsule thickness of PTMC10 was the lowest, at just 47.7 % of that of PTMC. Therefore, the Ebselen-loaded coating presents promising applications in cardiovascular stents.

In the present study, ethanolic extracts from the extract of unshelled seeds of Cannabis sativa L. were used to produce films in order not to generate additional waste, taking into view a circular economy. Combinations of apple pectin and citrus pectin in a ratio of 80:20 were used. Film samples containing 0.5, 1.0 and 2.5 [wt%] of the extract were extruded. Antimicrobial, mechanical and barrier properties of the obtained films were tested. Samples with 0.5 [wt%] showed a WVTR of 16.98 [g/m²d]. The water vapour barrier properties of the films decreased with an increase in the amount of extract used. As the amount of extract increased, the transparency of the films decreased linearly to 12.84 [%] (0.5 [wt%]), 4.90 [%] (1.0 [wt%]) and 4.99 [%] (2.5 [wt%]). It was observed that the brightness of the samples decreased with increasing concentration, due to the presence of higher levels of phenolic compounds. Tests carried out showed that the prepared films exhibited inhibitory activity against all micrograms tested. All prepared films had antibacterial activity against the Salmonella typhimurium strain. Similarly, in the case of L. monocytogenes.