br Materials and methods br Results and

Materials and methods
Results and discussion
Conclusion The preparation of acrylic nanoparticles as aminosugar carriers could not be achieved by direct functionalization of poly(t-butyl acrylate) particles with saccharide groups. A four-step procedure starting from a protected derivative of D-galactose for the preparation of glycomonomers was preferred. With an optimized method, nanoparticles with a size between 50 and 150 nm were obtained with limited coagulation and absence of micrometric objects. Once the isopropylidene protective groups were hydrolyzed, these nanoparticles were functionalized with dodecylamine with a rate higher than 80%, to form the biocidal moities C12Gal. While the free C12Gal Pamidronate Disodium receptor completely inhibited the growth of fungal strain H. resinae for concentrations as low as 2 × 10−5 mol·mL−1, its activity was not as pronounced when functionalized on the particles. NP-C12Gal succeeded in slowing down the growth of H. resinae, but did not allow total inhibition of mycelial growth. It is possible that the hydrolysis of the acrylate functions to release C12Gal was too slow to lead to an action as effective as that of the aminosugar alone.
Acknowledgments
Introduction Mucormycoses are life-threatening emerging infections that mainly affect immunocompromised and diabetic patients but may also occur in immunocompetent patients following trauma [1]. These infections, which are caused by several species in the order Mucorales [2], are generally difficult to treat for several reasons, including delayed diagnosis, acute disease progression, angioinvasion and tissue necrosis, in addition to primary resistance to many currently available antifungal drugs [3], [4]. Furthermore, amphotericin B (AmB), posaconazole and isavuconazole are the only drugs used for treatment of mucormycosis in humans [5], [6]. Owing to improved isolate identification methods [7] and reliable antifungal susceptibility testing techniques [8], [9], a more comprehensive picture of the antifungal profiles of Mucorales species has been obtained in recent years. Various animal models of mucormycosis have also contributed to evaluation of the antifungal efficacy of several drugs. Although Mucorales fungi have long been considered a homogeneous group with respect to antifungal susceptibility, it is now clear that this trait differs between species of this order [10]. However, the clinical significance of these species-dependent susceptibility patterns remains unknown and further studies in this area are warranted. Even the most active drugs against Mucorales species are associated with suboptimal treatment efficacy. Therefore, new strategies such as combination therapy have been the focus of much recent research both in vitro and in vivo using animal models. The aim of this review was to summarise recent data regarding the in vitro activity and in vivo efficacy of antifungal drugs against members of Mucorales and to identify areas in need of improvement.
Mucorales species diversity Human mucormycoses are caused by a wide range of pathogenic species. More than 25 Mucorales species belonging to no fewer than 10 genera have been reported to infect humans (Table 1). The phylogeny and taxonomy of the Mucorales have been substantially revised in recent years based on molecular data [11]. Several new cryptic species have been identified within various genera, including Lichtheimia, Mucor, Apophysomyces and Saksenaea (Table 1), and in some cases different morphological varieties have been shown to in fact belong to the same biological species (e.g. Rhizopus microsporus). Furthermore, certain species have been reassigned to a different genus (e.g. Mucor irregularis, formerly Rhizomucor variabilis). Precise (i.e. molecular) identification of isolates is of great importance to improve our knowledge of the epidemiology of mucormycosis [5]. Sequencing of the internal transcribed spacer (ITS) region is the recommended method for molecular identification of Mucorales species [5], [7]. Indeed, given its high interspecies and low intraspecies variability, the ITS region is one of the most useful targets for DNA barcoding of this group. The biological diversity of the Mucorales also has an impact on clinical practice, since the clinical form of mucormycosis is known to be linked to the particular species responsible. For example, Rhizopus arrhizus is more likely to result in the rhinocerebral form than other localisations of this disease [12]. Moreover, antifungal susceptibility profiles differ between species, although the clinical relevance of these species-specific profiles remains to be determined. Whilst highly important in improving our epidemiological knowledge of mucormycosis, in practice antifungal susceptibility testing is only marginally recommended for the guidance of treatment of patients with this disease [5].