Methylprednisolone sodium succinate

Acanthamoeba spp. can cause opportunistic infections, such as cutaneous acanthamoebiasis (CA). Little is known about the role of TLRs and cytokines in the host skin during Acanthamoeba spp. infections. The study aimed to examine the gene and protein expression of TLR3, TLR7, IFN-γ, and IL-23 in the skin of mice experimentally infected with a clinical strain of Acanthamoeba spp. male BALB/c mice were assigned to four groups: group I (control group I) - with normal immunity (C, n = 5); group II (control group II) - with reduced immunity induced by methylprednisolone sodium succinate (MPS; CS, n = 5); group III - amoeba-infected hosts with normal immunity (A, n = 12); and group IV- amoeba-infected hosts with reduced immunity induced by MPS (AS, n = 12). The skin sections (2 cm × 2 cm) were collected from the animals at 8, 16, and 24 days post-infection (dpi). TLR3, TLR7, IFN-γ, and IL-23 gene and protein expressions were analyzed by quantitative real-time PCR and immunohistochemical staining. In the immunocompetent hosts, we noted higher expressions of TLR3 and IL-23 at all-time points, except 8th dpi when IL-23 gene expression was downregulated compared to the control group. The mRNA expressions of TLR7 and IFN-γ were higher at 16 and 24 dpi in the skin of immunocompetent Acanthamoeba spp.-infected hosts than in the uninfected mice. In the course of acanthamoebiasis in the mice with reduced immunity, we found significant upregulation of TLR3, IL-23, and TLR7 gene expressions only at the beginning of infection compared to the control group. A similar relationship was observed for IFN-γ at 8 and 16 dpi. The pathophysiology of Acanthamoeba infection in the skin is complex. The data presented in this paper add new insight, but they are not sufficient to explain the role of the studied receptors and cytokines. The clinical picture and mechanisms of host response appear to be influenced by the route of infection, immunological status and microorganisms carried within the parasites. CA remains a multifactorial phenomenon.

Since the FDA approval of the first nanodrug Doxil® in 1995, twenty subsequent liposome and lipid nanoparticle (LNP) based drugs (of which 10 are nanodrugs), were approved by the FDA. The application of such drug-products was considerably boosted by the mRNA-LNP based vaccines used to stop the COVID-19 pandemic. Research on lipid-based vesicles and nanoparticles for drug delivery dates to the 1970s and has culminated in both continuous flow and extrusion-based fabrication processes for current state-of-the-art GMP industrial production of nanoliposomes and lipid nanoparticles. In this study, we compare these two approaches for the preparation of two PEGylated nanoliposome-based drug-products, keeping all other production steps leading to the final drug-product identical. One of these products, generic Doxil®, is remotely and actively loaded with the anthracycline doxorubicin (an amphipathic weak base) driven by a transmembrane ammonium gradient, while the other is methylprednisolone hemisuccinate (an amphipathic weak acid) remotely and actively loaded via a transmembrane acetate gradient. We demonstrate that a microfluidics-based micromixer approach yields equivalent or even better drug-products, especially since the downsizing by microfluidics is not performed above the temperature range of lipid phase transition. The main difference in the physico-chemical features is that size distribution of the microfluidics prepared PEGylated nano liposomes was significantly narrower and morphological analysis by cryo-TEM confirmed higher homogeneity. An additional advantage of the microfluidic approach is that it is a continuous production. Therefore, it enables the direct production of large volumes of high-quality nano-liposomal based drug-products.