Imized parameters developed with ITZ loaded COK 12 reveal that the loss in the drug release rate following 120 MPa Decitabine Dacogen compression was fully recovered by incorporating croscarmellose sodium to break apart the compacted granulates. This resulted in no release difference before and after compression. These results elucidate important parameters to consider for preparation of a successful scaled up manufacturing process of a dosage form based on ordered mesoporous silica carrier material. Invasive fungal infections caused by Candida species remain the major causes of mortality in immunocompromised patients. Although Candida albicans remains the predominant agent of nosocomial infections, an increasing number of infections have been attributed to non albicans species, such as Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida lusitaniae, and Candida krusei, emerging over recent years as opportunistic pathogens. Now, C. glabrata is often the second or third most common cause of candidiasis after C. albicans. C. glabrata infections can be mucosal or systemic and are common in immunocompromised patients or those with diabetes mellitus. C. glabrata is of special importance not only because of a recent increase in its frequency, but also because of its innately reduced susceptibility to antifungal agents, specifically the azoles, and readily mutates in vitro and in vivo and acquires a second azole resistance rapidly following short term exposure to the azole derived agents. Consequently, C. glabrata infections are difficult to treat and are associated with a high mortality rate in compromised patients.
The cell surface of Candida species is known to be covered with polysaccharide mannan. The mannans of medically important Candida species contain different structures, which correspond to the species specific antigen. C. glabrata cells as well as C. albicans serotype A, C. tropicalis, C. lusitaniae Fludarabine cells are known to have the antigenic factor 6, which corresponds to the Man 2Man 2Man residue. The 1,2 linked mannose residue is specifically present in the cell wall mannan of some Candida species and cell wall polysaccharide of a few microorganisms. The 1,2 linked mannose residue produces a characteristic oligosaccharide conformation, produces a specific antigenicity, display adhesion, and strong immunomodulatory properties. The 1,2 linked mannose residues are also present in a glycolipid called phospholipomannan, which induces TNFynthesis through the toll like receptor 2. On the other hand, linkedmannose residues are present in the cell wall polysaccharides of all of the common fungi and yeasts. Especially, the mannose residues, which have been shown to be the ligand of receptors, or lectins, such as the mannose receptor, mannan binding protein, Dectin 2, and the dendritic cell specific intercellular adhesion molecule 3 grabbing non integrin , are molecules known to be involved in host pathogen interactions, i.e. the so called innate immunity. The difference in the structure and/or composition of the cell wall mannan as well as other cell surface components, such as the protein and glucan, are known to affect the virulence of the Candida species. It has been reported that deletion of the 1,2 mannosyltransferase gene.