Adriamycin loading and release characteristics of albumin-heparin conjugate microspheres

Biodegradable ion-exchange microspheres, prepared from a prefabricated conjugate of albumin and heparin were investigated as carriers for adriamycin. The ion-exchange microspheres could be loaded with adriamycin giving payloads up to 33% w/w, depending on the heparin content of the conjugate. In vitro adriamycin release depended on the ionic strength of the release medium. In ion containing media, for instance saline, 90% of the drug was released within 45 min, whereas in non-ionic media, such as distilled water, only 30% was released. Drug release profiles could be modelled by combining ion-exchange kinetics and diffusion controlled drug release models

Albumin-heparin microspheres as carriers for cytostatic agents

Much work has been done on adriamycin-loaded albumin microspheres (Alb-MS) for chemoembolization [1–4], the rationale being that site-specific drug delivery may increase the therapeutic efficacy of the drug. Alb-Ms are being investigated because of their biocompatibility and because the degradation products of these microspheres are non-toxic. However, these microspheres have some disadvantages (i.e. drug loading during the microsphere preparation, low payloads, large burst effects). These disadvantages can be overcome by the incorporation of heparin (a highly negatively charged mucopolysaccharide). Albumin-heparin microspheres were prepared (i) by crosslinking of soluble albumin and heparin first using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and subsequently glutaraldehyde (Alb-Hep-MS) and (ii) by crosslinking a preformed soluble conjugate of heparin and albumin with glutaraldehyde (Alb-Hep-Conj-MS). Albumin-heparin microspheres could be loaded with adriamycin after microsphere preparation giving payloads of 15–30%. Preliminary in vitro adriamycin release experiments showed that Alb-Hep-Conj-MS exhibit sustained release properties. Furthermore ion-exchange properties could be observed both with Alb-Hep-MS and Alb-Hep-Conj-MS. In vitro and in vivo toxicity experiments with Alb-Hep-MS showed no adverse effects

Preparation and characterization of albumin-heparin microspheres

Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsphere stabilization in one step. The first technique was superior since it allowed better control over the composition and the homogeneity of the microspheres. Microspheres could be prepared with a diameter of 5¿35¿m. The size could be controlled by adjusting the emulsification conditions. The degree of swelling of the microspheres was sensitive to external stimuli, and increased with increasing pH and decreasing ionic strength of the medium

Adriamycin-loaded albumin-heparin conjugate microspheres for intraperitoneal chemotherapy

Adriamycin-loaded albumin-heparin conjugate microspheres (ADR-AHCMS) were evaluated as possible intraperitoneal (i.p.) delivery systems for site-specific cytotoxic action. The biocompatibility of the microspheres after intraperitoneal injection was tested first. 1 day after i.p. administration of empty as well as drug-loaded AHCMS to male Balb/c mice, only a moderate increase in i.p. neutrophils was measured. 3 days after injection neutrophil levels were comparable with the controls. No significant increases in the numbers of other cell types were observed, indicating an acute inflammatory response which can be considered to be mild. Antitumour efficacy was tested in an L1210 tumour-bearing mouse model and in a CC531 tumour-bearing rat model. The use of ADR-AHCMS leads to longer survival times of mice and improved tumour growth delay in rats, as compared with untreated controls and free drug treated animals. In both animal models higher adriamycin doses were initially tolerated if the drug was formulated in microspheres, although long-term adriamycin toxicity effects were evident in all treated groups. Doses and dosage schedules may be optimized to further reduce the toxic effects of the drug

North Korean CO emissions reconstruction using DMZ ground observations, TROPOMI space-borne data, and the CMAQ air quality model

Emission uncertainty in North Korea can act as an obstacle when developing air pollution management plans in the country and neighboring countries when the transboundary transport of air pollutants is considered. This study introduces a novel approach for adjusting and reallocating North Korean CO emissions, aiming to complement the limited observational and emissions data on the country's air pollutants. We utilized ground observations from demilitarized zone (DMZ) and vertical column density (VCD) data from a TROPOspheric Monitoring Instrument (TROPOMI), which were combined with the Community Multi-Scale Air Quality (CMAQ) chemistry transport model simulations. The Clean Air Support System (CAPSS) and Satellite Integrated Joint Monitoring of Air Quality (SIJAQ) emissions inventories served as the basis for our initial simulations. A two-step procedure was proposed to adjust both the emission intensity and the spatial distribution of emissions. First, air quality simulations were conducted to explore model sensitivity to changes in North Korean CO emissions with respect to ground concentrations. DMZ observations then constrained these simulations to estimate corresponding emission intensity. Second, the spatial structure of North Korean CO emission sources was reconstructed with the help of TROPOMI CO VCD distributions. Our two-step hybrid method outperformed individual emissions adjustment and spatial reallocation based solely on surface or satellite observations. Validation using ground observations from the Chinese Dandong site near the China-North Korea border revealed significantly improved model simulations when applying the updated CO emissions. The adjusted CO emissions were 10.9 times higher than those derived from the bottom-up emissions used in this study, highlighting the lack of information on North Korean pollutants and emission sources. This approach offers an efficient and practical solution for identifying potential missing emission sources when there is limited on-site information about air quality on emissions

Clinical associations and prognostic value of MRI-visible perivascular spaces in patients with ischemic stroke or TIA: a pooled analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH

Paricle identification at VAMOS++ with machine learning techniques

Multi-nucleon transfer reaction between 136Xe beam and 198Pt target was performed using the VAMOS++ spectrometer at GANIL to study the structure of n-rich nuclei around N=126. Unambiguous charge state identification was obtained by combining two supervised machine learning methods, deep neural network (DNN) and positional correction using a gradient-boosting decision tree (GBDT). The new method reduced the complexity of the kinetic energy calibration and outperformed the conventional method improving the charge state resolution by 8%