Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.
Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.
Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.
Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules. 相似文献
The scarring response after a penetrant central nervous system injury results from the interaction between invading leptominingeal/pericyte-derived fibroblasts and endogenous reactive astrocytes about the wound margin. Extracellular matrix and scar-derived axon growth inhibitory mole- cules fill the lesion site providing both a physical and chemical barrier to regenerating axons. Dec orin, a small leucine-rich chondroitin-dermatan sulphate proteoglycan expressed by neurons and astrocytes in the central nervous system, is both anti-fibrotic and anti-inflammatory and attenu- ates the formation and partial dissolution of established and chronic scars. Here, we discuss the potential of using Decorin to antagonise scarring in the central nervous system. 相似文献
We explored the potential of Smac mimetics, which antagonize Inhibitor of Apoptosis (IAP) proteins, for chemosensitization of neuroblastoma (NB). Here, we report that Smac mimetics, e.g. BV6, prime NB cells for chemotherapeutics including the topoisomerase II inhibitor doxorubicin (DOX) and vinca alkaloids such as Vincristine (VCR), Vinblastine (VBL) and Vinorelbine (VNR). Additionally, BV6 acts in concert with DOX or VCR to suppress long-term clonogenic growth. While BV6 causes rapid downregulation of cellular IAP (cIAP)1 protein and nuclear factor-kappaB (NF-κB) activation, DOX/BV6- or VCR/BV6-induced apoptosis occurs independently of NF-κB or TNFα signaling, since overexpression of dominant-negative IκBα superrepressor or the Tumor Necrosis Factor (TNF)α-blocking antibody Enbrel fail to block cell death. Mechanistic studies reveal that Receptor-interacting protein (RIP)1 is required for DOX/BV6-, but not for VCR/BV6-induced apoptosis, since transient or stable knockdown of RIP1 or the pharmacological RIP1 inhibitor necrostatin-1 significantly reduce apoptosis. By comparison, VCR/BV6-mediated apoptosis critically depends on the mitochondrial pathway. VCR/BV6 cotreatment causes phosphorylation of BCL-2 during mitotic arrest, enhanced activation of BAX and BAK and loss of mitochondrial membrane potential (MMP). Additionally, overexpression of BCL-2 profoundly suppresses VCR/BV6-induced apoptosis. Thus, BV6 sensitizes NB cells to chemotherapy-induced apoptosis via distinct initial signaling mechanisms depending on the chemotherapeutic drug. These findings provide novel mechanistic insights into Smac mimetic-mediated chemosensitization of NB. 相似文献
ObjectiveCavum veli interpositi (CVI) is a potential space below the splenium of corpus callosum and sometimes presents as a cyst.Materials and methodsIn this prospective cross-sectional study, 360 fetuses with normal second trimester scan and 152 s trimester fetuses with structural abnormalities were included.ResultsThe CVI cysts were more common in fetuses with brain anomaly compared to normal fetuses and fetuses with extra-central nervous system (CNS) anomalies (23% vs 18.3% and 18% respectively; p value < 0.01). The mean size of cysts in normal fetuses, fetuses with extra-CNS anomalies and fetuses with brain abnormalities was 4.6 mm, 5.8 mm and 9.2 mm respectively. There was a significant difference between cysts size in normal fetuses and fetuses with brain anomalies (p value < 0.01) and the cut-point was 7.1 mm.ConclusionThe prevalence of CVI cysts is more in fetuses with brain anomaly. Fetuses with a cyst size >7.1 mm need a more detailed brain examination. 相似文献
Neurologic sequelae remain a common and destructive problem in patients with acute kidney injury. The objective of this study was to evaluate the possible neuroprotective effect of erythropoietin (EPO) on motor impairments following bilateral renal ischemia (BRI) in two time points after reperfusion: short term (24 h) and long term (1 week). Male Wistar rats underwent BRI or sham surgery. EPO or saline administration was performed 30 min before surgery (1000 U/kg, i.p.). Explorative behaviors and motor function of the rats were evaluated by open field, rotarod, and wire grip tests. Plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were significantly enhanced in BRI rats 24 h after reperfusion. BRI group had only an increased level of BUN but not Cr 1 week after reperfusion. Impairment of balance function by BRI was not reversed by EPO 24 h after reperfusion, but counteracted 7 days after renal ischemia. Muscle strength had no significant differences between the groups. BRI group had a decrease in locomotor activity, and EPO could not reverse this reduction in both time points of the experiment. Although EPO could not be offered as a potential neuroprotective agent in the treatment of motor dysfunctions induced by BRI, it could be effective against balance dysfunction 1 week after renal ischemia. 相似文献
β-Carbolines (BCs) are considered to be endogenous toxins and have been proposed as possible causative candidates inducing Parkinson's disease (PD). However, there is controversy about the effect and also effective dose of these compounds in the etiology of PD. This study was designed to further examine the effect of norharman (NH), a BC which in mammalian brain occurs at high levels in the substantia nigra, on the development of Parkinsonism-like behaviors in rats. A small amount (4μl) of NH solution at 2 or 200ng/ml was unilaterally injected into either striatum or substantia nigra (SN) by stereotaxic surgery. The development of Parkinsonism was assessed by three conventional behavioral tests, compared to the effects of unilateral 6-hydroxydopamine (6-OHDA) - induced lesions in the nigrostriatal pathway. An apomorphine-induced rotational test revealed no Parkinsonism-like behavior in the NH treated groups. However, rats that received the high concentration of NH into their SN showed significant biased swings in the elevated body swing test. In a rotarod test, NH treated groups showed relatively weak motor performance and their learning patterns were close to that of the 6-OHDA treated rats. Considering that the rotational test is only valid in animals with severe Parkinsonism, but time spent on the rotating rod correlates inversely with severity of Parkinsonism, our results indicate that a single exposure to low amounts of NH is effective in producing moderate Parkinsonism-like behavioral symptoms, possibly through a neurotoxic effect of this agent on the SN dopaminergic neurons. 相似文献