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Highly functionalized drugs delivered via a drug delivery system are expected to have less side effects and higher accumulation rates compared to conventional anticancer drugs. An understanding of the kinetics of drugs contained within a delivery system is necessary to obtain the maximum therapeutic effect. We performed micro-elemental analysis of human pancreatic cancer cells treated with cis-diamminedichloroplatinum(II) (CDDP)-containing polymeric micelles. The results showed that the platinum signals were distributed inside the cellular nuclei and the cytoplasm indicating that CDDP was delivered into the cells. The results from this study will be useful for designing an optimum carrier for platinum-containing anticancer drugs.
Microencapsulated anti-RLIP76 was tested in vivo using C3He/J mice to determine the increasing of antitumor effects by chemotherapeutic agent efflux inhibition during chemoradiotherapy. Microcapsules were produced by spraying a mixture of 3.0% hyaluronic acid, 2.0% alginate, 3.0% H2O2, and 0.3 mmol carboplatin onto a mixture of 0.3 mol FeCl2 and 0.15 mol CaCl2. Microcapsules were subcutaneously injected into MM46 tumors previously inoculated into the left hind legs of C3He/J mice. Subsequent radiotherapy consisted of tumor irradiation with 10 Gy or 20 Gy60Co. The antitumor effects of microcapsules were tested by measuring tumor size and monitoring tumor growth. Three types of adverse effects were considered: fuzzy hair, loss of body weight, and mortality. Carboplatin levels were monitored using particle-induced X-ray emission (PIXE) and a micro-PIXE camera. Anti-RLIP76 inhibited the efflux of carboplatin from tumor tissue, which led to an increase in the concentration of carboplatin. Higher carboplatin concentration significantly increased the combined antitumor effect of radiation and chemotherapy. A significant decrease in adverse effects was also observed with microencapsulated anti-RLIP76.
We have been developing microcapsules that release anticancer drug with response to radiation. We attempted to decrease the diameter of capsules. Then, two categories were tested in VIVO in C3He mice: (1) the antitumor effect in combination with radiation and subcutaneously injected nanocapsules, (2) the kidnetics of nanocapsules when they were injected intravenously.
Microcapsules were produced by spraying a mixture of 3.0 % hyaluronic acid, 2.0 % alginate, 3.0 % H2O2, and 0.3 mmol carboplatin (Pt containing anticancer drug) onto a mixture of vibrated 0.3 mol FeCl2 and 0.15 mol CaCl2. The antitumor effect was measured by measuring tumor diameter every day. The kinetics of microcapsules were expressed as the numbers of capsules in 5 views (25 × 25 μm) of micro PIXE camera and Pt concentration of quantiative PIXE.
The generated microcapsules 752 ± 64 nm, which were significantly downsized relative to previous capsules. The accumulations of capsules in lungs, liver, and kidneys were decreased by downsizing, whereas those of tumors were increased. By adjusting Pt concentration in tumor, there were no significant differences in antitumor effect between not downsized and downsized microcapsules with combination with radiation.
Decreased trapping of downsized microcapsules to lungs, liver, and kidneys, also increased trapping in tumors will lead to new targeted chemoradiotherapy via intravenous injection of microcapsules.
The aim of this study was to determine whether oxygen-releasing microcapsules could be used to sensitize cancer cells to kill by radiation. The microcapsules were generated by spraying a mixture of 0.1% alginate and hyaluronic acid into a 0.3 mmol/l solution of CaCl2 and FeCl2. These were then subcutaneously injected around a MM48 tumor (a cell line derived from human breast cancer) in the left hind legs of C3H/HeN mice, and tumors were dosed with 60Co γ-ray radiation. We showed that the oxygen released from the microcapsules enhanced the anti-tumor effect of radiation treatment via the generation of oxygen radicals.
We have been developing microcapsules that release anticancer drugs in response to radiation with an aim of targeted delivery and increasing the efficacy of anticancer drugs by a combination of these drugs with radiation. The aim of this study was to micronize microcapsules by adding carbonated water to the core material of microcapsules, which releases the anticancer drugs in response to radiation. The core material of microcapsules was prepared by mixing 0.1 g of hyaluronic acid and 0.2 g of alginate into 5 mL of carbonated water. The mixture was sprayed onto a 0.3 mmoL/L solution of calcium chloride (CaCl2) and ferrous chloride (FeCl2) using an ultrasound disintegrator. The vibration of the ultrasound disintegrator generated microbubbles in the carbonated water, which micronized the microcapsules. Intravenous injection of the micronized microcapsules to tumor-bearing mice showed that the micronized microcapsules passed more efficiently through the capillaries of lungs or kidneys, which resulted in increased delivery of microcapsules to the tumors and increased the anticancer effect.
In this paper, we used microcapsules releasing liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) with/without carboplatin in response to radiation to image and treat MM48 breast cancer in C3He/N mice in two radiation sessions. The micro-particle-induced X-ray emission (PIXE) camera and quantitative PIXE were used to image and measure the release of nanoparticles from the microcapsules. In session one, iopamiron and computed tomography (CT)-detectable microcapsules containing P-selectin and LPH-NP were mixed with a solution of alginate, hyaluronate, ascorbate, and P-selectin. This solution was sprayed into an FeCl2 solution containing VEGFR-1/2 antibodies (Abs). The microcapsules obtained were injected intravenously into mice, and after 9 h, the mice were exposed to 10 or 20 Gy (140 keV) of X-ray radiation. Anti-VEGFR-1/VEGFR-2 microcapsules accumulated around tumors and released P-selectin and the iopamiron-labeled LPH-NP in response to the first radiation. The iopamiron-containing nanoparticles were detected by CT, allowing detection of MM48 tumors by CT. In the second session, the microcapsules released LPH-NH that delivered carboplatin into the tumor cells. This treatment had a significant antitumor effect (P<0.05)(P<0.05). The micro-PIXE camera and quantitative PIXE successfully imaged and measured the release of contents from microcapsules. Our results indicate that targeted nanoparticles allow for accurate detection and treatment of tumors.
We report an elemental analysis of murine solid tumors treated with cisplatin-incorporated polymeric micelles (NC-6004) to evaluate the concentration of the drug in the tumor tissue using conventional particle-induced X-ray emission (PIXE) analysis, as well as the spatial distribution in the tumor section using sub-millimeter PIXE analysis. The results reveal that the platinum concentration in the tumor treated with NC-6004 was higher than in that treated with cisplatin, whereas no significant difference was found in platinum concentration between NC-6004 and cisplatin samples in the normal tissue. This suggests that NC-6004 can both provide therapeutic efficacy and reduce the side effects caused by conventional treatment using cisplatin. These results show that PIXE analysis is a powerful tool for research into drug delivery systems.
We aimed to image and treat the lung metastases of MM48 breast cancer cells in C3He/N mice by using microcapsules that release liposome-protamine-hyaluronic acid nanoparticles (LPH-NP) in response to two radiation sessions. In session one, computed tomography (CT)-detectable microcapsules containing P-selectin and 5% iopamiron were mixed with a 1 mL solution of 4% alginate, 3% hyaluronate, 1 mg ascorbate, and 1 μg/mL P-selectin. This was sprayed into 0.5 mmol/L FeCl2 containing 1 μg/mL VEGFR-1/2 antibodies (Abs). The mice were intravenously injected with microcapsules, which released the P-selectin, and then a CT study was performed to detect lung metastases. After the CT evaluation, the mice received 10 or 20 Gy (140 keV) of X-ray radiation to the lungs. In session two, carboplatin-LPH-NP was released into the tumor, which was treated with another dose of radiation. To do this, carboplatin LPH-NP was mixed with the cocktail used in session one and sprayed into 0.5 mmol/L FeCl2 containing 1 μg/mL anti-P-selectin Abs. Microcapsules (1 × 1010) were injected intravenously and then interacted with the P-selectin. The released carboplatin LPH-NP attacked lung metastases synergistically with radiation, which resulted in further reduction of the lung metastases.
The nanoparticles, which releases anticancer drug with response to radiation, were developed. Also, two categories were tested: (i) their ability to release anticancer drug in vitro; and (ii) their kinetics in the body, when they were injected through tail vein of BALB/c mice in vivo. To prepare the particles, hyaluronic acid and protamine were mixed into carboplatin solution, and reacted for 30 min in room temperature. Those particles were exposed to a single dose of 10 Gy of 140 KeV X-ray. Their ability to release carboplatin with response to radiation was expressed as the percentage of ruptured particles, basing on images of particles, using micro PIXE camera. The amount of released carboplatin was measured by quantitative PIXE method. The kinetics of particles in body was assessed by counting the number of particles, which were trapped in lungs, using micro PIXE camera. The mean diameter of particles was 743 ± 34 nm. By irradiation, 59.3 ± 7.23% of particles ruptured, and 95.9 ± 2.3% carboplatin was released from particles. The trapped particles in lungs were significantly reduced, when compared with previous alginate-hyaluronic particles.
Encapsulated protamine-hyaluronic acid particles containing carboplatin were prepared and their ability to release carboplatin was tested in vivo. Protamine–hyaluronic acid particles containing carboplatin were prepared by mixing protamine (1.6 mg) and hyaluronic acid (1.28 mg) into a 5 mg/mL carboplatin solution for 30 min at room temperature. A 1 mL solution of protamine–hyaluronic acid particles was poured into an ampule of COATSOME® EL-010 (Nichiyu, Tokyo, Japan), shaken three times by hand, and allowed to incubate at room temperature for 15 min. Following that, 10 or 20 Gy of 100 kiloelectronvolt (KeV) soft X-ray was applied. The release of carboplatin was imaged using a microparticle-induced X-ray emission (PIXE) camera. The amount of carboplatin released was expressed as the amount of platinum released and measured via quantitative micro-PIXE analysis. The diameter of the generated encapsulated particles measured 574±23 nm (mean ± standard error).
The release of carboplatin from the encapsulated protamine–hyaluronic acid particles was observed under a micro-PIXE camera. The amount of carboplatin released was 3.0±0.3 μg under 10 Gy of radiation, and 7.3±0.8 μg under 20 Gy of radiation, which was a sufficient dose for cancer treatment. However, 10 or 20 Gy of radiation is much greater than the dose used for clinical cancer treatment (2 Gy). Further research to reduce the radiation dose to 2 Gy in order to release sufficient carboplatin for cancer treatment is required.
Osthole, a coumarin compound mainly derived from Cnidium monnieri (L.), has attracted much interest from the scientific community owing to its multiple therapeutic properties. However, its pharmacological mechanism, pharmacokinetics, and toxicological effects are far from clear. Furthermore, the potential drug delivery platforms of osthole remain to be comprehensively delineated. The present review aimed to systematically summarize the most up-to-date information related to pharmacology, pharmacokinetics, and safety issues related to osthole, and discuss the investigations of novel drug delivery platforms. The information herein discussed was retrieved from authoritative databases, including PubMed, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure (CNKI) and so on, reviewing information published up until February of 2024. New evidence shows that osthole induces a sequence of therapeutic actions and has a moderate absorption rate and rapid metabolic characteristics. In addition, this phytoconstituent possesses potential hepatotoxicity, and caution should be exercised against the risk of the drug combination. Furthermore, given its needy solubility in aqueous medium and non-organizational targeting, novel drug delivery methods have been designed to overcome these shortcomings. Given the properties of osthole, its therapeutic benefits ought to be elucidated in a greater array of comprehensive research studies, and the molecular mechanisms underlying these benefits should be explored.
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OTHER REGIONS — NORTH AMERICA – Researchers Discover Most Powerful HIV Antibody.
High-Throughput Sequencing on a Next Generation Sequencer to Identify Specific Binders from a Phage Library
Antibody Solution Viscosity and Intermolecular Interactions: Considerations for Development of Highly Concentrated Formulations
Display of Membrane Proteins on a Viral Envelope for Antibody Generation
Sequence and Structural Determinants of Antigen Binding in Antibody CDR Loops
Enhancement of the Stability of Single Chain Fv Molecules with the Amino Acid Substitutions Predicted by High-Performance Computer
Thermal Stability of Camelid Single Domain VHH Antibody
Quantum dots (QDs), a type of semiconductor nanomaterial, have drawn a lot of attention because of their exceptional optical characteristics and prospective uses in biology and medicine. However, the presence of heavy hazardous metals in typical QDs, such as Cd, Pb and Hg, has posed a significant obstacle to their use. Therefore, it is essential to look for a workable substitute that would be nontoxic and have comparable optical characteristics to the traditional QDs. It has been determined that ternary I–III–VI QDs are appropriate substitutes. They emit light in the near-infrared range and have adjustable optical characteristics. They are valuable in a variety of biological applications because of their optical characteristics and can be easily bioconjugated with biomolecules for targeted imaging. Therefore, this review concentrates on the most recent developments in the usage of aqueous CIS QDs in biological, bioconjugated with biomolecules, nanomedical and drug delivery system applications.
The binding and acid-base equilibria of the two novel mesoporphyrin derivatives, PB07 and PB109 (quino[4,4a,5,6-efg]- annulated 7-demethyl-8-deethylmesoporphyrin and 2'-cyano-8'-formyl-N'-methyl-1',1a',5a',6'-tetrahydroacrido [4,5,5a,6-bcd]- annulated 2,3-dihydromesoporphyrin, resp.), which are promising agents for photodynamic therapy (PDT), were studied in aqueous solutions of different surfactants (Triton X-100 (TX-100), dodecyl maltoside (DDM), cetyltrimethylammonium bromide (CTAB), lithium dodecyl sulfate (LDS)) and phosphatidyl choline (PC) liposomes. In all cases, the porphyrins are solubilized at neutral/alkaline pH in monomeric form and remain micelle/liposome-bound independently of their ionization state. The dissociation constants of the solubilized porphyrins are found to be influenced by the charge of the surface groups of the carrier. The protonation of pyrrole/quinoline nitrogens of the studied porphyrins is facilitated in the following order: LDS ≫TX-100 (DDM, PC liposomes) > CTAB. The dissociation constants of PB07 carboxylic groups are similar in neutral/cationic micellar and liposome solutions and are significantly decreased for LDS-bound pigment. The results provide necessary information for the optimization of delivery systems for PB07 and PB109 when applied as sensitizers in PDT.
Mesostructured chitosan-coated Fe3O4 nanoparticles (CS-coated Fe3O4 NPs) were synthesized by a facile one-step solvothermal method via using chitosan as a surface-modification agent. Subsequently, the surfaces of CS-coated Fe3O4 NPs were successfully conjugated with folic acid (FA) molecules to obtain FA–CS-coated Fe3O4 NPs for improving targeted drug delivery. The morphology, chemical component and magnetic property of as-prepared composite nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning transmission electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA) and vibrating sample magnetometer (VSM). Furthermore, doxorubicin hydrochloride (DOX) as a model drug was encapsulated for investigating drug release pattern in vitro. The results show that the magnetization saturation value of FA–CS-coated Fe3O4 NPs was about 28.5 emu/g, exhibiting superparamagnetic properties and mesostructure. DOX could be loaded to FA–CS-coated Fe3O4 NPs with high capacity about 27.9%, and the release rate of DOX could be adjusted by the pH value. This work demonstrates that the prepared magnetic nanoparticles have potential applications in the treatment of cancer as targeting drug delivery carriers.
Doxorubicin (DOX) plays an important part in lymphoma treatment. However, various side effects on normal tissues restrict its clinical use. Nanocarriers connected by Gly–Phe–Leu–Gly (GFLG) can be equipped with the advantages of nanoparticles (NPs), their enhanced permeability and retention (EPR) effect, and surface modifiability. Nanocarriers can also be specifically enzymatically hydrolyzed by cathepsin (Cath) B, a kind of enzyme highly expressed in tumor cells. In this work, we proposed a novel drug delivery system comprising GFLG conjugated with copper sulfide (CuS) NPs loaded with DOX. The system, designated as CuS-GFLG-DOX, could be used for NP-based targeted combination chemotherapy. Results showed that the drug delivery system had an appropriate diameter, good dispersibility, high encapsulation efficiency and high drug loading. The system also exhibited an excellent targeting of lymphoma cells and an enhanced antitumor activity. The possible pathway to induce cytotoxic effects was Bcl-2/caspase-mediated apoptosis pathway. In conclusion, CuS-GFLG-DOX could precisely deliver drugs to lymphoma cells and could be a novel and promising therapeutic option for lymphoma.
The present study outlines a straightforward approach for designing a novel drug delivery system based on bacterial nanocellulose composites containing curcumin-loaded graphene quantum dots (BNC/CUR/GQDs) for antibacterial and wound healing applications. The nanocomposite was made of interconnected plates with uniform thicknesses around 2mm. The scanning electron microscope (SEM) image of the prepared BNC nanocomposite showed a uniform and porous morphology composed of the microfibrils having an average diameter of 120nm, which contributes to both drug inclusion and drug release in a controllable fashion. The designed system biosynthesized by Acetobacter xylinum demonstrated an optimum drug loading capacity and controlled release profile. The drug loading content and drug release efficiency were calculated around 31% and 61%. Agar diffusion test indicated that the introduction of GQDs into the BNC matrix conspicuously improved the growth inhibition of bacteria, and gram-negative and gram-positive bacterial strains were measured 21.6mm and 21.5mm, respectively. The cell viability of 92.3% was obtained for the BNC, while the cell viability of the designed system was measured at around 88.07%. Consequently, the incorporation of curcumin-loaded graphene quantum dots into bacterial nanocellulose matrices can open up a new insight into the production of high-performance wound dressing supplies.
Current clinical practice in ocular disease treatment dosage forms primarily relies on eye drops or eye ointments, which face significant challenges in terms of low bioavailability profiles, rapid removal from the administration site, and thus ineffective therapeutic efficiency. Hydrogel has several distinct properties in semi-solid thermodynamics and viscoelasticity, as well as diverse functions and performance in biocompatibility and degradation, making it extremely promising for overcoming the challenges in current ocular treatment. In this review, the most recent developments in the use of hydrogel biomaterials in ocular therapy are presented. These sophisticated hydrogel biomaterials with diverse functions, aimed at therapeutic administration for ocular treatment, are further classified into several active domains, including drug delivery system, surface repair patch, tissue-engineered cornea, intraocular lens, and vitreous substitute. Finally, the possible strategies for future design of multifunctional hydrogels by combining materials science with biological interface are proposed.
The real-time tracking of a single molecule is a very useful technique to demonstrate the dynamics of drugs in vivo. We have succeeded in capturing the specific delivery of trastuzumab conjugated with a Quantum dot and fluorescent substances of various sizes in animal models. These results revealed the particular movements of drugs or particles in the tumor tissues. Knowledge of the detailed movement of particles incorporated in drugs can lead to improvement of the design of drugs. We are applying this single molecular imaging technique to estimate the efficacy of a drug delivery system.
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