The study indicates that the improved aqueous solubility of the cocrystals leads to improved bioavailability of IND. Thus, the cocrystals are a viable alternative solid form that can improve the dissolution rate and bioavailability of poorly soluble drugs.

The aim of the present study was to investigate the effect of Soluplus ® on the solubility of atorvastatin calcium and to develop a solid dispersion formulation that can improve the oral bioavailability of atorvastatin calcium. We demonstrated that Soluplus ® increases the aqueous solubility of atorvastatin calcium. Several solid dispersion formulations of atorvastatin calcium with Soluplus ® were prepared at various drug : carrier ratios by spray drying. Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in each solid dispersion, and the 2 : 8 drug : carrier ratio provided the highest degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in rats revealed that the 2 : 8 dispersion significantly improved the oral bioavailability of atorvastatin. This study demonstrates that spray-dried Soluplus ® solid dispersions can be an effective method for achieving higher atorvastatin plasma levels.

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Since the pioneering research of Bangham et al. in 1965, liposomes have attracted a large amount of interest as potential carriers of various bioactive molecules for clinical applications. However, scaling-up conventional methods of liposome preparation has been proven to be challenging. Compared with conventional methods, processes that use supercritical fluid (SCF)-CO2 require a reduced amount of organic solvent, are relatively fast and simple to perform, and yield stable and more uniform liposomes. A number of studies have demonstrated that SCF-CO2 methods might be suitable for industrial-scale manufacturing of liposomes. In this review there are two topics being discussed. We provide an overview of liposomal drug products and aim to describe the physicochemical properties of liposomes prepared using various SCF methods. We review all of the available literature on SCF-CO2-based liposomes and focus on the future applications of these innovative technologies in industrial-scale liposome preparation.

Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.

Purpose: Neutrophils play a critical role in defending against threats such as microbial infection, yet their activation during innate immune response incites collateral damage to healthy tissues. We have previously shown that corneal injury induces mast cells to express the neutrophil chemoattractant CXCL2. Here we delineate the mechanism of injury-induced, non-IgE-mediated mast cell activation at the ocular surface.Methods: Corneal injury was induced by mechanical removal of the epithelium and anterior stroma in mast cell deficient (cKit W-sh ) and C57BL/6 mice using Algerbrush II. Corneas were analyzed for frequencies of total CD45 + inflammatory cells, CD11b + Ly6G + neutrophils, and cKit + FcεR1 + mast cells using flow cytometry. Mast cells were stimulated with different inflammatory factors known to increase during corneal injury (IL-33, IL-1β, IL-36γ, IL-6, SDF1α and Substance P) and assessed for the secretion of β-hexosaminidase, tryptase and CXCL2 using ELISA. IL-33 neutralizing antibody (1 mg/ml) was administered locally for mast cell inhibition in vivo.Results: Mast cell deficient mice failed to recruit early neutrophils to the injured corneas. IL-33 stimulation upregulated CXCL2 secretion by mast cells. Corneal injury resulted in amplified expression of IL-33 at the cornea and epithelium was identified as its primary source. Topical neutralization of IL-33 at the ocular surface inhibited mast cell activation, limited neutrophil infiltration and reduced corneal inflammatory haze, normalizing tissue architecture following ocular injury.Conclusions: These data implicate IL-33 in mast cell activation and early neutrophil recruitment in non-allergic inflammation, suggesting IL-33 as a potential therapeutic target in inflammatory disorders of the ocular surface.

Purpose The benefit of post-mastectomy radiation therapy (PMRT) in patients with breast cancer who achieve ypN0 following neoadjuvant chemotherapy (NAC) has not yet been established. This study aimed to identify the role of PMRT in patients who achieve ypN0 according to molecular subtype. Methods We identified patients initially suspected with axillary disease who achieved ypN0 following NAC. From 13 institutions of the Korean Radiation Oncology Group between 2005 and 2011, a total of 189 patients were included in the analysis. Effects of PMRT on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) were evaluated for different molecular subtypes. Results In all patients, the prognostic effect of PMRT on LRC, DFS, or OS was not significant. Subgroups analysis showed that the effect of PMRT on LRC was different according to molecular subtype ( p for interaction = 0.019). PMRT was associated with greater LRC in the luminal subtype ( p = 0.046), but not in other subtypes. Conclusion In patients who achieve ypN0 following NAC and mastectomy, PMRT shows no additional survival benefits for any molecular subtype.