0000000000182312
AUTHOR
Leah Pretsch
Monophosphoryl lipid A coating of hydroxyethyl starch nanocapsules drastically increases uptake and maturation by dendritic cells while minimizing the adjuvant dosage.
Enhancing delivery of antigens to dendritic cells (DCs) is essential for the induction of vigorous antigen-specific cellular immune responses. Aim of the present study was to evaluate the properties of hydroxyethyl starch nanocapsules (HES-NCs) functionalized with anti-CD40, anti-DEC205, interferon-γ (IFNγ) and/or monophosphoryl lipid A (MPLA) with respect to the overall uptake, the released cytokine profile, and the influence on phenotypic maturation of human monocyte-derived DCs using flow cytometry, confocal microscopy and enzyme-linked immunosorbent assays. NC uptake by DCs was significantly enhanced by functionalizing NCs with anti-CD40 or MPLA. With respect to the cytokine profile and…
Nanocapsules generated out of a polymeric dexamethasone shell suppress the inflammatory response of liver macrophages.
Abstract Dexamethasone (DXM) is a synthetic glucocorticoid with anti-inflammatory properties. Targeted delivery of dexamethasone to inflammatory cells, e.g. macrophages and Kupffer cells represents a promising approach to minimize side effects. The aim of the present study was to induce a targeted transport of novel DXM-based biodegradable nanocapsules to phagocytic cells. Nanocapsules (NCs) consisting of a hydroxyethylated glucose polymer (hydroxyethyl starch, HES) shell with encapsulated DXM and NCs synthesized exclusively in inverse miniemulsion out of DXM were investigated. Non-parenchymal murine liver cells served as target cells. HES-DXM NCs were predominantly incorporated by Kupffer …
Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses
Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver…
Extensive Antibiotic and Antimalarial Prescription Rate among Children with Acute Febrile Diseases in the Lake Victoria Region, Tanzania
Abstract Objectives Acute mosquito-borne febrile diseases pose a threat to children in the Sub-Saharan-Africa with ∼272 000 children dying worldwide from malaria in 2018. Although the awareness for malaria in this area has increased due to improved health education, the apparent decline of actual malaria cases has not affected clinical practice significantly. This study collected clinical and epidemiologic data of children presenting with acute febrile diseases in order delineate their diagnostic and therapeutic management. Methods A hospital-based cross-sectional clinical study was conducted at the Sekou Toure Regional Referral Hospital in Tanzania. Children between 1 month and 12 years of…
MPLA-coated hepatitis B virus surface antigen (HBsAg) nanocapsules induce vigorous T cell responses in cord blood derived human T cells.
Chronic hepatitis B virus (HBV) infection is the most prevalent serious liver infection in the world. A frequent route of infection represents mother-to-child transmission. Efficient control of HBV replication depends on antigen-specific cellular immune response mediated by dendritic cells (DCs). Aim of the present study was to evaluate optimized adjuvant combinations, efficiently maturing monocyte-derived neonatal and adult dendritic cells (moDCs). In addition, the potential of polymeric HBsAg-nanocapsules (HBsAg-NCs) was investigated regarding up-take by moDCs and the subsequent induction of specific T cell responses in a human co-culture model. Simultaneous stimulation of moDCs with MPLA…
Enhanced in vivo targeting of murine nonparenchymal liver cells with monophosphoryl lipid A functionalized microcapsules.
A broad spectrum of infectious liver diseases emphasizes the need of microparticles for targeted delivery of immunomodulatory substances to the liver. Microcapsules (MCs) are particularly attractive for innovative drug and vaccine formulations, enabling the combination of antigen, drugs, and adjuvants. The present study aimed to develop microcapsules characterized by an enhanced liver deposition and accelerated uptake by nonparenchymal liver cells (NPCs). Initially, two formulations of biodegradable microcapsules were synthesized from either hydroxyethyl starch (HES) or mannose. Notably, HES-MCs accumulated primarily in the liver, while mannose particles displayed a lung preference. Functio…