Abstract:The main objective of the present study was to investigate the hemo and immune compatibility of gliadin nanoparticles as a function of particle size. Gliadin nanoparticles of different size were prepared using a modified antisolvent nanoprecipitation method. The hemolytic potential of gliadin nanoparticles was evaluated using in vitro hemolysis assay. Phagocytic uptake of gliadin nanoparticles was studied using rat polymorphonuclear (PMN) leukocytes and murine alveolar peritoneal macrophage (J774) cells. In vi… Show more
“…[110,112] A too large size (e.g., >500 nm) may facilitate particle clearance by monocytes and macrophages and/or prevent the uptake of these particles by the target tumor cells. [112,113] Meanwhile, particles with a too small size (e.g., under 20 nm) are more prone to rapid renal clearance, [16,110] or cannot offer enough energy to bend cell membranes and enter the target cells. [85,111] In addition, reduced particle size leads to a larger total surface area, which may cause faster and less controlled drug release.…”
Section: Conception Of Colloidal Pecs From Hamentioning
nanocomplexes, [8,9] nanocomposites, [10,11] nanoassemblies [12] and coacervates. [13,14] Such colloidal systems, especially when prepared from biopolymers, have been extensively investigated due to their promising properties for numerous applications in biomedical fields. [1] Their merits come from the combination of three aspects: nanomedicine, biomaterials, and green chemistry. With the emergence of nanomedicine, the use of nanocarriers can offer tremendous advantages in drug encapsulation and delivery, namely enhancing the chemical stability of drugs and improving drug solubility and bioavailability. [15] Due to their small size and the possibility of surface modification with biological ligands or molecular imprinting, nanocarriers can easily cross biological barriers, which have limited pore sizes (fenestrations) under 1 micron in most cases, then target and enter the tissues or cells of interest. [16,17] Due to these aspects and the possibility of controlling drug distribution and release through particle engineering, nanocarriers can thus reduce systemic side effects and enhance the therapeutic efficacy of drugs. [15] Nanosystems can also offer unique advantages for biomedical imaging with their ability of sensing, image enhancement, and incorporating concomitantly therapeutic agents for theranostics, that is, simultaneous therapeutic and diagnostic applications. [18][19][20] When constructed from biomaterials, especially naturally occurring polysaccharides or proteins, PECs can become significantly biocompatible and biodegradable with much less immunogenicity and toxicity. [21] Besides such biorelevant aspects, the elaboration of biopolymerbased PECs is also in accordance with green chemistry principles since their preparation process usually requires only gentle mixing of polyelectrolyte solutions at room temperature, which is a simple and rapid procedure without the need for chemical agents, surfactants, organic solvents or high mechanical or thermal energy. [15] Beyond the above-mentioned basic advantages, the potential of colloidal PEC systems is increased by the inherent biological and chemical properties of individual constituent polymers. Hyaluronic acid (HA), also called hyaluronan to generally mention both its acid and salt forms, has been one of the most common polyanions among several biopolymers reported so far for the elaboration of colloidal PECs. The significant attention dedicated to HA in biomedical fields is associated with its unique advantages, stemming from not only its outstanding biocompatibility but also interesting biological activities. [22] Hyaluronic acid (HA) is a naturally occurring polysaccharide which has been extensively exploited in biomedical fields owing to its outstanding biocompatibility. Self-assembly of HA and polycations through electrostatic interactions can generate colloidal polyelectrolyte complexes (PECs), which can offer a wide range of applications while being relatively simple to prepare with rapid and "green" processes. The advantages of colloidal HA-base...
“…[110,112] A too large size (e.g., >500 nm) may facilitate particle clearance by monocytes and macrophages and/or prevent the uptake of these particles by the target tumor cells. [112,113] Meanwhile, particles with a too small size (e.g., under 20 nm) are more prone to rapid renal clearance, [16,110] or cannot offer enough energy to bend cell membranes and enter the target cells. [85,111] In addition, reduced particle size leads to a larger total surface area, which may cause faster and less controlled drug release.…”
Section: Conception Of Colloidal Pecs From Hamentioning
nanocomplexes, [8,9] nanocomposites, [10,11] nanoassemblies [12] and coacervates. [13,14] Such colloidal systems, especially when prepared from biopolymers, have been extensively investigated due to their promising properties for numerous applications in biomedical fields. [1] Their merits come from the combination of three aspects: nanomedicine, biomaterials, and green chemistry. With the emergence of nanomedicine, the use of nanocarriers can offer tremendous advantages in drug encapsulation and delivery, namely enhancing the chemical stability of drugs and improving drug solubility and bioavailability. [15] Due to their small size and the possibility of surface modification with biological ligands or molecular imprinting, nanocarriers can easily cross biological barriers, which have limited pore sizes (fenestrations) under 1 micron in most cases, then target and enter the tissues or cells of interest. [16,17] Due to these aspects and the possibility of controlling drug distribution and release through particle engineering, nanocarriers can thus reduce systemic side effects and enhance the therapeutic efficacy of drugs. [15] Nanosystems can also offer unique advantages for biomedical imaging with their ability of sensing, image enhancement, and incorporating concomitantly therapeutic agents for theranostics, that is, simultaneous therapeutic and diagnostic applications. [18][19][20] When constructed from biomaterials, especially naturally occurring polysaccharides or proteins, PECs can become significantly biocompatible and biodegradable with much less immunogenicity and toxicity. [21] Besides such biorelevant aspects, the elaboration of biopolymerbased PECs is also in accordance with green chemistry principles since their preparation process usually requires only gentle mixing of polyelectrolyte solutions at room temperature, which is a simple and rapid procedure without the need for chemical agents, surfactants, organic solvents or high mechanical or thermal energy. [15] Beyond the above-mentioned basic advantages, the potential of colloidal PEC systems is increased by the inherent biological and chemical properties of individual constituent polymers. Hyaluronic acid (HA), also called hyaluronan to generally mention both its acid and salt forms, has been one of the most common polyanions among several biopolymers reported so far for the elaboration of colloidal PECs. The significant attention dedicated to HA in biomedical fields is associated with its unique advantages, stemming from not only its outstanding biocompatibility but also interesting biological activities. [22] Hyaluronic acid (HA) is a naturally occurring polysaccharide which has been extensively exploited in biomedical fields owing to its outstanding biocompatibility. Self-assembly of HA and polycations through electrostatic interactions can generate colloidal polyelectrolyte complexes (PECs), which can offer a wide range of applications while being relatively simple to prepare with rapid and "green" processes. The advantages of colloidal HA-base...
“…8 c), elucidating no serious adverse effects and elucidating good biocompatibility of ZnO/WG nanospheres in vivo 42 . These results generally indicated that the administration of ZnO/WG nanospheres was biocompatible in mice 43 , 44 . Figure 8 Safety evaluation.…”
The development of inorganic antibacterial agents that impart antibacterial properties to biomaterials has attracted wide attention. The paper introduced a kind of hybrid nanosphere antibacterial agent composed of wheat gliadin (WG) and zinc oxide (ZnO), with antibacterial efficacy and low toxicity. The ZnO/WG hybrid nanospheres were environment-friendly integrated by molecular self-assembly co-precipitating and freeze-drying transformation, and were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), atomic absorption spectroscopy (AAS), specific surface and pore size analysis, bacteriostasis test, reactive oxygen species (ROS) determination and safety evaluation. It was found that the prepared hybrid nanospheres were composed of two components, WG and ZnO, with a diameter scope of 100–200 nm; the content of ZnO in the hybrid nanospheres can reach 46.9–70.2% (w/w); the bacteriostasis tests proved that the prepared ZnO/WG nanospheres generating ROS, have a significant inhibitory effect on E. coli and S. aureus; furthermore, the ZnO/WG nanospheres are relatively safe and highly biocompatible in cells and mice. Therefore, the prepared novel ZnO/WG hybrid nanospheres were supposed to apply in the preparation of anti-infective wound dressings, tissue engineering skin scaffold materials, food, and cosmetics preservatives, and so on.
“…Figures 4 and 5 indicate that the nanoformulation enabled not only a reduction in the frequency of administration but also an improvement in the efficacy of KS-58. Smaller-sized nanoparticles are reportedly less immunogenic 32 , 33 . KS-58 NPs have been administered multiple times to both wild-type (Fig.…”
Single amino acid mutations of Ras occur in 30% of human cancers. In particular, K-Ras(G12D) has been detected in the majority of intractable colorectal and pancreatic cancers. Although efforts to target K-Ras(G12D) are currently underway, no effective drugs are available. We previously found that the K-Ras(G12D)-inhibitory bicyclic peptide KS-58 exhibits antitumor activity against syngeneic colon and orthotopic grafted pancreatic tumors; however, pristine KS-58 is difficult to handle because of low water solubility and it requires frequent administration to obtain sufficient antitumor activity. In this study, we used a nanoformulation of KS-58 prepared with the highly biocompatible surfactant Cremophor® EL (CrEL) to improve water solubility and reduce the dosing frequency. Nanoformulations of KS-58 with CrEL dramatically improved its water solubility and increased its stability. Weekly intravenous administration of KS-58 nanoparticles (NPs) suppressed the growth of CT26 and PANC-1 cell-derived tumors in vivo, and fluorescent bioimaging indicated that the NP-encapsulated near-infrared fluorescent probe indocyanine green selectively accumulated in the tumor and was safely excreted through the kidneys following intravenous injection. Histopathological analysis of CT26 tumors and Western blotting of PANC-1 tumors revealed that KS-58 NPs reduced ERK phosphorylation, a downstream signal of K-Ras(G12D). Our results suggest that KS-58 NPs represent a novel therapeutic agent for treating colorectal and pancreatic cancers.
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