Short Half-life Time Research Articles

Selective adsorption of Ba2+ using chemically modified alginate beads with enhanced Ba2+ affinity and its application to 131Cs production

The 131Cs radioisotope with a short half-life time and high average radiation energy can treat the cancer effectively in prostate brachytherapy. The typical 131Cs production processes have a separation step of the cesium from 131Ba to obtain a high specific radioactivity. Herein, we suggested a novel 131Cs separation method based on the Ba2+ adsorption of alginate beads. It is necessary to reduce the affinity of alginate beads to cesium ions for a high production yield. The carboxyl group of the alginate beads was replaced by a sulfonate group to reduce the cesium affinity while reinforcing their affinity to barium ions. The modified beads exhibited superior Ba2+ adsorption performances to native beads. In the fixed-bed column tests, the saturation time and adsorption capacity could be estimated with the Yoon-Nelson model in various injection flow rates and initial concentrations. In terms of the Cs elution, the modified alginate showed better performance (i.e., an elution over 88%) than the native alginate (i.e., an elution below 10%), indicating that the functional group modification was effective in reducing the affinity to cesium ions. Therefore, the separation of cesium from the barium using the modified alginate is expected to be an additional option to produce 131Cs.

Combination Therapy with Fluoxetine and the Nucleoside Analog GS-441524 Exerts Synergistic Antiviral Effects against Different SARS-CoV-2 Variants In Vitro.

The ongoing SARS-CoV-2 pandemic requires efficient and safe antiviral treatment strategies. Drug repurposing represents a fast and low-cost approach to the development of new medical treatment options. The direct antiviral agent remdesivir has been reported to exert antiviral activity against SARS-CoV-2. Whereas remdesivir only has a very short half-life time and a bioactivation, which relies on pro-drug activating enzymes, its plasma metabolite GS-441524 can be activated through various kinases including the adenosine kinase (ADK) that is moderately expressed in all tissues. The pharmacokinetics of GS-441524 argue for a suitable antiviral drug that can be given to patients with COVID-19. Here, we analyzed the antiviral property of a combined treatment with the remdesivir metabolite GS-441524 and the antidepressant fluoxetine in a polarized Calu-3 cell culture model against SARS-CoV-2. The combined treatment with GS-441524 and fluoxetine were well-tolerated and displayed synergistic antiviral effects against three circulating SARS-CoV-2 variants in vitro in the commonly used reference models for drug interaction. Thus, combinatory treatment with the virus-targeting GS-441524 and the host-directed drug fluoxetine might offer a suitable therapeutic treatment option for SARS-CoV-2 infections.

Improving temozolomide biopharmaceutical properties in glioblastoma multiforme (GBM) treatment using GBM-targeting nanocarriers

Glioblastoma multiforme (GBM) is the most common primary brain cancer. GBM has aggressive development, and the pharmacological treatment remains a challenge due to GBM anatomical characteristics’ (the blood–brain barrier and tumor microenvironment) and the increasing resistance to marketed drugs, such as temozolomide (TMZ), the first-line drug for GBM treatment. Due to physical–chemical properties such as short half-life time and the increasing resistance shown by GBM cells, high doses and repeated administrations are necessary, leading to significant adverse events. This review will discuss the main molecular mechanisms of TMZ resistance and the use of functionalized nanocarriers as an efficient and safe strategy for TMZ delivery. GBM-targeting nanocarriers are an important tool for the treatment of GBM, demonstrating to improve the biopharmaceutical properties of TMZ and repurpose its use in anti-GBM therapy. Technical aspects of nanocarriers will be discussed, and biological models highlighting the advantages and effects of functionalization strategies in TMZ anti-GBM activity. Finally, conclusions regarding the main findings will be made in the context of new perspectives for the treatment of GBM using TMZ as a chemotherapy agent, improving the sensibility and biological anti-tumor effect of TMZ through functionalization strategies.

Superoxide Ion and Singlet Oxygen Photogenerated by Metalloporphyrin-Based Metal-Organic Frameworks for Highly Efficient and Selective Photooxidation of a Sulfur Mustard Simulant.

The exploration of highly efficient materials for the degradation of chemical warfare agents has been a longstanding task for preventing human exposure. Herein, we report a series of metal-organic frameworks (MOFs) M-TCPP-La based on metallo-tetra(4-carboxyphenyl)porphyrin and LaIII, which were applied to selectively oxidize 2-chloroethyl ethyl sulfide (CEES, a sulfur mustard simulant) as heterogeneous photocatalysts. After irradiation from a commercial blue light-emitting diode (LED), both superoxide ion and singlet oxygen were generated by M-TCPP-La and involved in selective oxidization of CEES to 2-chloroethyl ethyl sulfoxide (CEESO). Notably, a very short half lifetime (2.5 min) was achieved using Fe-TCPP-La as the photocatalyst. In comparison to currently utilizing singlet oxygen and hydrogen peroxide as oxidizing agents, this work employing both singlet oxygen and superoxide ion represents a new and effective strategy of detoxification of mustard gas.

Long-Term Analgesia following a Single Application of Fentanyl Transdermal Solution in Pigs

Introduction: In animal research, obtaining efficient and constant pain control is regulatory but challenging. The gold standard pain management consists of opioid analgesic administration, such as buprenorphine or fentanyl extended-release patches. However, as in all drugs with a short half-life time, repeated buprenorphine administrations are needed, leading to multiple injections that affect the research protocol. On the other hand, fentanyl patch efficacy is discussed in some species. These elements highlight the need of an optimal formulation of analgesic drugs for laboratory animals. In this study, we investigated how Recuvyra®, a fentanyl transdermal solution (FTS), validated in dog perioperative pain management, could provide sustained analgesia after a single topical administration in pigs in a surgical context. Methods: A total of 11 minipigs were used in this study. As a preliminary experiment, two different doses were tested as a single application on five pigs: two pigs at full dose (2.6 mg/kg) and three pigs at half dose (1.3 mg/kg). Plasma fentanyl dosages were performed during 4 consecutive days, using liquid chromatography with tandem mass spectrometry detection. The efficacy of FTS was then evaluated in a perioperative period. Six minipigs benefited from a surgical intervention comprising a laparotomy. The FTS was blotted on the skin in a single application 20 min before the surgical incision and plasma fentanyl dosages, clinical examination (body weight, food intake, heart rate, and body temperature) and pain assessment were performed for 7 consecutive days. Results: During the preliminary experiment, all fentanyl concentrations reached the minimum effective concentration (MEC) extrapolated in pigs (fentanylemia ≥0.2 ng/mL) throughout the 4 days. The half dose was chosen for the next step of the study. After the surgical intervention, all plasma fentanyl concentrations remained above the MEC up to 7 days post administration. Pig clinical examinations and pain evaluations showed efficient and constant pain control at the half dose, and few adverse events were observed. Discussion and Conclusion: This study confirms the pharmacological and clinical efficacy of FTS at 1.3 mg/kg in pigs throughout at least 7 postoperative days following laparotomy. The clinical analgesic effect of FTS appears more efficient and well-tolerated than the one observed with repeated injections of buprenorphine. This analgesic drug formulation could be universally used in animal research to provide optimal perioperative pain management and long-term analgesia.

An Antibody-like Polymeric Nanoparticle Removes Intratumoral Galectin-1 to Enhance Antitumor T-Cell Responses in Cancer Immunotherapy.

Antibodies have shown potential to deplete immunosuppressive factors in tumor tissues. However, intrinsic drawbacks, including time-consuming processes in preparation, high cost, and short half-life time, greatly restrict their applications. In this work, we report an antibody-like polymeric nanoparticle (APN) that is capable of specifically capturing and removing galectin-1 in tumor tissues, thereby enhancing the antitumor T-cell responses. The APN is composed of an albumin-polymer hybrid nanoparticle (core) and an acid-responsive PEG shell. The core of the APN contains multiple recognition units and Tuftsin peptides to capture target factors and activate macrophage-mediated phagocytosis, respectively. By employing galactose as recognition units, the APN facilitated the phagocytosis of galectin-1 in tumor tissues, thereby improving the antitumor responses of tumor-infiltrating T cells. Since the recognition units in the APN can be further replaced to capture and remove other peptides/proteins, the APN provides a feasible approach for the development of synthetic nanoformulations to regulate biological systems and treat diseases.

Ameliorating quercetin constraints in cancer therapy with pH-responsive agarose-polyvinylpyrrolidone -hydroxyapatite nanocomposite encapsulated in double nanoemulsion

Despite quercetin (QC) promising features for cancer therapy, low solubility, poor permeability, and short biological half-life time significantly confine its application in cancer therapy. In this study, a novel approach is developed to improve loading efficiency and attain quercetin sustained-release concurrently. In this direction, hydrogel nanocomposite of agarose (AG)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAp) was loaded with QC. Incorporating HAp nanoparticles in the AG-PVP hydrogel improved the loading efficiency up to 61%. Also, the interactions between nanoparticle, drug, and hydrogel polymers rendered the nanocomposite pH-responsive at acidic conditions and controlled the burst release at neutral conditions. Then, QC-loaded hydrogel was encapsulated into the water in oil in water nanoemulsions to further sustain the drug release. As a result, the pH-responsive release of QC with prolonged-release over 96 h was observed. In more detail, according to the Korsmeyer-Peppas mathematical model, the mechanism of release was anomalous (diffusion-controlled) at pH 7.4 and anomalous transport (dissolution-controlled) at pH 5.4. The presence of all nanocomposite components was confirmed with FTIR analysis, and XRD results approved the incorporation of QC in the fabricated nanocomposite. The homogeneous surface of the nanocomposite in FESEM images showed good compatibility between components. The zeta potential analysis confirmed the good stability of the nanocarriers. Besides, the fabricated AG-PVP-HAp-QC platform showed significant cytotoxicity on MCF-7 cells compared to QC as a free drug (p < 0.001) and to quercetin-loaded AG-PVP (AG-PVP-QC) (p < 0.001) with enhanced apoptosis induction after the addition of HAp. Accordingly, this delivery platform ameliorated loading and sustained-release of QC, as well as its anticancer activity by releasing the drug at an effective therapeutic level over a long period to induce apoptosis. Thus, turning this drug delivery system into a potential candidate for further biomedical applications.

Estimation of cooling water activation in high-energy heavy ion medical accelerator

The estimation of air, material, and cooling water activation is essential for designing a robust nuclear safety protocol for high-energy heavy ion medical accelerators. Demineralized cooling water activation is simulated for the C-12 ion beam medical accelerator (synchrotron) with a maximum energy of 430 MeV/u. Three conservative scenarios are proposed for the estimation of demineralized cooling water activation. Simulations were performed by using a combination of MCNPX2.7.0 and VCINDER codes. Simulation parameters were optimized to match the volume of the cooling water in the accelerator system. The sums of the ratios of specific activities to unrestricted release limits were calculated for the three scenarios as a function of decay time. All activity concentrations are far less than the corresponding unrestricted release limits after a 1-day decay time because the sums of the ratios are all less than 1.0. Noticeable hazardous radioactive elements were found to be H-3, Be-7, and C-11 which have relatively long half-life times. Although hazardous radioactive elements with relatively short half-life times (within 10 min), such as N-13, O-14, and O-15, are also produced in large concentrations, there are no unrestricted release limits specified in the table issued by the National and International Radiation Protection Ordinances. The estimation of cooling water activation is useful for designing a nuclear safety protocol for high-energy heavy ion medical accelerator facilities. Specifically, the results suggest that the direct discharge of the cooling water waste into the environment (in case of an accident or the end of the life cycle of cooling water) must not be permitted. A separate reservoir for cooling water waste collection is recommended with a dedicated real-time measuring equipment to measure the concentrations of H-3, Be-7, C-11, N-13, O-14, and O-15 separately.

Development and validation of samples stabilization strategy and LC-MS/MS method for simultaneous determination of clevidipine and its primary metabolite in human plasma: Application to clinical pharmacokinetic study in Chinese healthy volunteers

A feasible LC-MS/MS method with reliable stabilizers consisted of sodium fluoride, ascorbic acid and formic acid was developed and validated for the determination of clevidipine and its primary metabolite (H152/81) in human plasma. Sodium fluoride existing in the vacutainer tubes was used to inhibit esterase activity to protect the clevidipine from hydrolysis as soon as blood was collected. Ascorbic acid and formic acid were added to the separated plasma samples to avoid the oxidation and further hydrolysis of clevidipine and H152/81. The further sample preparation was accomplished through a single step liquid-liquid extraction (LLE) by ethyl acetate. The chromatography separation was carried out on an ACE Excel 3 μm SuperC18 (2.1 × 50 mm, id, ACE, United Kingdom) column with gradient elution using 10 mM ammonium acetate water solution and methanol as the mobile phase. Detection was performed in the negative ion electrospray ionization mode using multiple reaction monitoring (clevidipine: m/z 454.1 → 234.0; clevidipine-d7: m/z 461.1 → 240.1; H152/81: m/z 354.0 → 208.0; H152/81-13CD3: m/z 358.0 → 212.0). The method exhibited good linearity over the concentration ranges of 0.100 to 40.0 ng/mL for clevidipine and 5.00 to 400 ng/mL for H152/81. The intra- and inter-batch precision and accuracy of clevidipine and H152/81 were all within the acceptable criteria. The method was successfully applied to a pharmacokinetic study of clevidipine and H152/81 in healthy Chinese volunteers following 8 mg/h intravenous infusion of clevidipine butyrate injectable emulsion for 0.5 h. The results showed that clevidipine was rapidly eliminated with a short half-life time of 0.244 ± 0.125 h and a maximum concentration of 25.2 ± 7.09 ng/mL. H152/81 was detectable in the plasma samples up to 48.5 h with a half-life time of 10.7 ± 2.30 h and a maximum plasma concentration of 301 ± 38.1 ng/mL.

Enhancement radiation-induced apoptosis in C6 glioma tumor-bearing rats via pH-responsive magnetic graphene oxide nanocarrier

5-iodo-2-deoxyuridine (IUdR) has been demonstrated to induce an appreciable radiosensitizing effect on glioblastoma patients, but due to the short circulation half-life times and failure to pass through the blood-brain barrier (BBB), its clinical use is limited. Accordingly, in this study, we used magnetic graphene oxide (NGO/SPIONs) nanoparticles coated with PLGA polymer as a dynamic nanocarrier for IUdR and, evaluated its sensitizing enhancement ratio in combination with a single dose X-ray at clinically megavoltage energies for treatment of C6 glioma rats. Nanoparticles were characterized using Zetasizer and TEM microscopy, and in vitro biocompatibility of nanoparticles was assessed with MTT assay. IUdR/MNPs were intravenously administered under a magnetic field (1.3 T) on day 13 after the implantation of C6 cells. After a day following the injection, rats exposed with radiation (8 Gy). ICP-OES analysis data indicated an effective magnetic targeting, leading to remarkably improved penetration through the BBB. In vivo release analysis with HPLC indicated sustained release of IUdR and, prolonged the lifespan in plasma (P < .01). In addition, our findings revealed a synergistic effect for IUdR/MNPs coupled with radiation, which significantly inhibited the tumor expansion (>100%), prolonged the survival time (>100%) and suppressed the anti-apoptotic response of glioma rats by increasing Bax/Bcl-2 ratio (2.13-fold) in compared with the radiation-only. In conclusion, besides high accumulation in targeted tumor sites, the newly developed IUdR/MNPs, also exhibited the ability of IUdR/MNPs to significantly enhance radiosensitizing effect, improve therapeutic efficacy and increase toxicity for glioma-bearing rats.

Erythrocyte-mimicking paclitaxel nanoparticles for improving biodistributions of hydrophobic drugs to enhance antitumor efficacy

Recent decades have witnessed several nanocrystal-based hydrophobic drug formulations because of their excellent performance in improving drug loading and controlling drug release as mediate drug forms in tablets or capsules. However, the intravenous administration of drug nanocrystals was usually hampered by their hydrophobic surface properties, causing short half-life time in circulation and low drug distribution in tumor. Here, we proposed to enclose nanocrystals (NC) of hydrophobic drug, such as paclitaxel (PTX) into erythrocyte membrane (EM). By a series of formulation optimizations, spherical PTX nanoparticles (PN) with the particle size of around 280 nm were successfully cloaked in erythrocyte membrane, resulting in a PTX-NP-EM (PNM) system. The PNM could achieve high drug loading of PTX (>60%) and stabilize the particle size significantly compared to PN alone. Besides, the fluorescence-labeling PNM presented better tumor cell uptake, stronger cytotoxicity, and higher drug accumulation in tumor compared to PN. Finally, the PNM was found to be the most effective against tumor growth among all PTX formulations in tumor-bearing mice models, with much lower system toxicity than control formulation. In general, the PNM system with high drug-loading as well as superior bio-distributions in vivo could be served as a promising formulation.

Poly(3-hydroxybutyrate)/poly(amine)-coated nickel oxide nanoparticles for norfloxacin delivery: antibacterial and cytotoxicity efficiency.

Sustained release dosage forms enable prolonged and continuous release of a drug in the gastrointestinal tract for medication characterized by a short half lifetime. In this study, the effect of blending polyamine on poly(3-hydroxybutyrate) (PHB) as a carrier for norfloxacin (NF) was studied. The prepared blend was mixed with different amounts of NiO nanoparticles and characterized using FTIR analysis, X-ray diffraction analysis, thermogravimetric analysis, dynamic light scattering, transmission electron microscopy and scanning electron microscopy. It was found that the drug released from the nanocomposite has a slow rate in comparison with NiO, PHB, and PHB/polyamine blend. The highest ratio of NiO content to the matrix (highest NF loading), leads to a slower rate of drug release. The release from the nanocomposites showed a faster rate at pH = 2 than that at pH = 7.4. The mechanisms of NF adsorption and release were studied on PHB/polyamine–3% NiO nanocomposite. In addition, the antimicrobial efficacy of nanocomposites loaded with the drug was determined and compared with the free drug. Inclusion of NiO into PHB/polyamine showed a higher efficacy against Streptococcus pyogenes and Pseudomonas aeruginosa than the free NF. Moreover, the cytotoxicity of PHB/polyamine–3% NiO against HePG-2 cells was investigated and compared with PHB and PHB/polyamine loaded with the drug. The most efficient IC50 was found for NF@PHB/polyamine–3% NiO (29.67 μg mL−1). No effect on cell proliferation against the normal human cell line (WISH) was observed and IC50 was detected to be 44.95 and 70 μg mL−1 for NiO nanoparticles and the PHB/polyamine–3% NiO nanocomposite, respectively indicating a selectivity of action towards tumor cells coupled with a lack of cytotoxicity towards normal cells.

Fast carbonylation reaction from CO2 using plasma gas/liquid microreactors for radiolabeling applications

The major challenge for 11C-radiolabelling is the short half-life time of 11C (t1/2 = 20.4 min) – in this study, a novel efficient process combining microfluidics and plasma is proposed for fast carbonylation reactions from CO2.

Ripening-resistance of Pd on TiO2(110) from first-principles kinetics.

Suppressing sintering of supported particles is of importance for the study and application of metal-TiO2 system. Theoretical study of Ostwald ripening of TiO2(110)-supported Pd particles would be helpful to extend the understanding of the sintering. In this paper, based on density functional theory (DFT), the surface energy of Pd and the total activation energy (the sum of formation energy and diffusion barrier) of TiO2-supported Pd were calculated. Since the total activation energy is mainly contributed from the formation energy, it is indicated that the ripening of Pd particles would be in the interface control limit. Subsequently, the calculated surface energy and total activation energy were used to simulate Ostwald ripening of TiO2(110)-supported Pd particles. As a result, in comparison with larger particles, smaller particles would worsen the performance of ripening-resistance according to its lower onset temperature and shorter half-life time. The differences on ripening-resistance among different size particles could be mitigated along with the increase of temperature. Moreover, it is verified that the monodispersity can improve ripening resistance especially for the smaller particles. However, the different performances of the ripening originating from difference of the relative standard deviation are more obvious at higher temperature than lower temperature. This temperature effect for the relative standard deviation is the inverse of that for the initial main particle size. It is indicated that the influence of dispersity of TiO2(110)-supported Pd particles on ripening may be more sensitive at higher temperature. In this contribution, we extend the first principle kinetics to elaborate the ripening of Pd on TiO2(110). It is expected that the information from first principle kinetics would be helpful to the study in experiments.

Highly variable mRNA half-life time within marine bacterial taxa and functional genes.

SummaryMessenger RNA can provide valuable insights into the variability of metabolic processes of microorganisms. However, due to uncertainties that include the stability of RNA, its application for activity profiling of environmental samples is questionable. We explored different factors affecting the decay rate of transcripts of three marine bacterial isolates using qPCR and determined mRNA half‐life time of specific bacterial taxa and of functional genes by metatranscriptomics of a coastal environmental prokaryotic community. The half‐life time of transcripts from 11 genes from bacterial isolates ranged from 1 to 46 min. About 80% of the analysed transcripts exhibited half‐live times shorter than 10 min. Significant differences were found in the half‐life time between mRNA and rRNA. The half‐life time of mRNA obtained from a coastal metatranscriptome ranged from 9 to 400 min. The shortest half‐life times of the metatranscriptome corresponded to transcripts from the same clusters of orthologous groups (COGs) in all bacterial classes. The prevalence of short mRNA half‐life time in genes related to defence mechanisms and motility indicate a tight connection of RNA decay rate to environmental stressors. The short half‐life time of RNA and its high variability needs to be considered when assessing metatranscriptomes especially in environmental samples.

Controlled release of huperzine-A from biocompatible copolymer microspheres

Huperzine-A (Hup-A) is a reversible acetylcholinesterase inhibitor used for patients suffering from Alzheimer’s disease. Hup-A has to be administered daily because of its short half-life time and narrow therapeutic range, making it less suitable for clinical use. In the present study, we studied its controlled drug delivery using biodegradable microspheres to avoid frequent dosing. Hup-A-loaded microspheres were prepared by an emulsion crosslinking method using a mixture of water and oil. Calcium chloride was used as a crosslinker. Primarily, we prepared sodium alginate (NaAlg) microspheres and investigated the in vitro release. The in vitro release studies were carried out successively at three different pH (1.2, 6.8 and 7.4) values for 2 h. To increase the durability of the NaAlg microspheres, NaAlg was blended with acrylamide (AAm)-grafted poly(vinyl alcohol) (PVA). It was determined that the presence of the PVA-g-AAm increased the physical resistance of the microspheres and also increased the amount of Hup-A loading and release. Additionally, the effect of the NaAlg/PVA-g-AAm (w/w) blend ratio, drug/polymer (w/w) ratio, crosslinker concentration and crosslinking period on the release of Hup-A was investigated. The prepared microspheres were characterized using Fourier transform infrared spectroscopy, differential scanning calorimetry and scanning electron microscopy.

Competitive Association of Antibiotics with a Clay Mineral and Organoclay Derivatives as a Control of Their Lifetimes in the Environment.

A Na-smectite clay mineral (Na-Mt) was exchanged with two concentrations of benzyldimethyltetradecyl ammonium chloride cationic surfactant up to one time the cation exchange capacity. Nonionic organoclay was prepared with polyoxyethylene (20) oleyl ether (Brij-O20) nonionic surfactant at one concentration. The resulting organoclays displayed lateral layer organization of the surfactants within their interlayer space.. The adsorption properties of these organoclays and the starting raw clay mineral were evaluated for three extensively used antibiotic pharmaceutical products: the amoxicillin (AMX), the sulfamethoxazole (SMX), and the trimethoprim (TRI), recognized as recalcitrant compounds to conventional water treatments and to display a complex behavior for different pH and temperature experimental conditions. Besides showing short half-life time with possible degradation by UV radiation, these antibiotics associated with mineral phases cause serious environmental issues of which the toxic effect can be exacerbated in the presence of other chemical compounds. From the set of data obtained by complementary techniques: UV and Fourier transform infrared spectroscopy, high-performance liquid chromatography coupled with mass spectrometry, and X-ray diffraction, it appears that the nonionic organoclay shows its versatility for the adsorption of individual molecules as well as a pool of antibiotics. The mixing of the three antibiotics showing different electric charged species (cations, anions, and zwitterions) mimics the natural context drives to a deep modification of the adsorption behavior onto the different materials that can act as possible carrier mineral phases in aquatic environment. These competition effects can be measured through the significant decrease of the KF Freundlich constants for AMX in the presence of other molecules (or electrolytes), whereas TRI and SMX, by their possible association, create a synergistic effect that favors their adsorption on the whole layered materials.

Expanding the Applicability of the Metal Labeling of Biomolecules by the RIKEN Click Reaction: A Case Study with Gallium-68 Positron Emission Tomography.

Radiolabeled biomolecules with short half-life times are of increasing importance for positron emission tomography (PET) imaging studies. Herein, we demonstrate an improved and generalized method for synthesizing a [radiometal]-unsaturated aldehyde as a lysine-labeling probe that can be easily conjugated into various biomolecules through the RIKEN click reaction. As a case study, 68 Ga-PET imaging of U87MG xenografted mice is demonstrated by using the 68 Ga-DOTA-RGDyK peptide, which is selective to αV β3 integrins.

Optimization of Protein and Peptide Drugs Based on the Mechanisms of Kidney Clearance.

Development of proteins and peptides into drugs has been considered as a promising strategy to target certain diseases. However, only few proteins and peptides have been approved as new drugs into the market each year. One major problem is that proteins and peptides often exhibit short plasma half-life times, which limits the application for their clinical use. In most cases a short half-life time is not effective to deliver sufficient amount of drugs to the target organs and tissues, which is generally caused by fast renal clearance and low plasma stability due to proteolytic degradation during systemic circulation, because that the most common clearance pathway of small proteins and peptides is through glomerular filtration by the kidneys. In this review, enzymatic degradation of proteins and peptides were discussed. Furthermore, several approaches to lengthen the half-life of peptides and proteins drugs based on the unique structures of glomerular capillary wall and the mechanisms of glomerular filtration were summarized, such as increasing the size and hydrodynamic diameter; increasing the negative charge to delay the filtration; increasing plasma protein binding to decrease plasma clearance.

Intervention strategies for prevention of remifentanil-induced postoperative hyperalgesia

Background Remifentanil is a ultra-short-acting μ-opioid receptor agonist. Because remifentanil possesses high efficacy, rapid onset, short half-life time and fast clearance, it has been widely used for anesthesia. However, the incidence of remifentanil-induced hyperalgesia (RIH) remains relatively high, which poses great challenges to postoperative management. Objective To explore the effective intervention strategy for the prevention of RIH. Content Like other opioid drugs, remifentanil, after repetitive and long-term administration, causes drug tolerance and pain hypersensitivity. RIH may follow central sensitization of both ascending and descending pathways to facilitate pain transduction. A large amount of clinical trials tried to prevent RIH using various medications, such as, agonists for α2-drenoreceptor, opioid drugs, antagonists for NMDA receptors, non-steroid anti-inflammatory drugs, and calcium channel blockers, etc. Trend Further studies in the field are required to advance the understanding of the development of RIH, which may result in better strategies to prevent and treat this condition. Key words: Remifentanil; Hyperalgesia; Prevention