In vivo intranasal delivery of coagulation factor IX: a proof-of-concept study.

Background: Hemophilia B (HB) is a bleeding disorder characterized by coagulation factor (F) IX (FIX) deficiency. The current standard-of-care for severe HB is prophylaxis with long-term repetitive intravenous (i.v.

Poloxamers Have Vaccine-Adjuvant Properties by Increasing Dissemination of Particulate Antigen at Distant Lymph Nodes.

Vaccine technology is still facing challenges regarding some infectious diseases, which can be addressed by innovative drug delivery systems. In particular, nanoparticle-based vaccines combined with new types of adjuvants are actively explored as a platform for improving the efficacy and durability of immune protection. Here, biodegradable nanoparticles carrying an antigenic model of HIV were formulated with two combinations of poloxamers, 188/407, presenting or not presenting gelling properties, respectively.

Induction of a strong and long-lasting neutralizing immune response by dPreS1-TLR2 agonist nanovaccine against hepatitis B virus.

Hepatitis B virus remains a major medical burden with more than 250 million chronically infected patients worldwide and 900,000 deaths each year, due to the disease progression towards severe complications (cirrhosis, hepatocellular carcinoma). Despite the availability of a prophylactic vaccine, this infection is still pandemic in Western Pacific and African regions, where around 6% of the adult population is infected. Among novel anti-HBV strategies, innovative drug delivery systems, such as nanoparticle platforms to deliver vaccine antigens or therapeutic molecules have been investigated.

Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines.

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid.

Sublingual protein delivery by a mucoadhesive patch made of natural polymers.

The sublingual mucosa is an appealing route for drug administration. However, in the context of increased use of therapeutic proteins, development of protein delivery systems that will protect the protein bioactivity is needed. As proteins are fragile and complex molecules, current sublingual formulations of proteins are in liquid dosage.

Synthesis and biological evaluation of thiophene and benzo[b]thiophene analogs of combretastatin A-4 and isocombretastatin A-4: A comparison between the linkage positions of the 3,4,5-trimethoxystyrene unit.

Combretastatin A-4 and isocombretastatin A-4 derivatives having thiophenes or benzo[b]thiophenes instead of the B ring were prepared and evaluated for their in cellulo tubulin polymerization inhibition (TPI) and antiproliferative activities. The presence of the benzo[b]thiophene ring proved to have a crucial effect as most of the thiophene derivatives, except those having one methoxy group, were inactive to inhibit tubulin polymerization into microtubules. The influence of the attachment position was also studied: benzo[b]thiophenes having iso or cis 3,4,5-trimethoxystyrenes at position 2 were 12-30-fold more active than the 3-regioisomers for the TPI activity.

Synthesis and biological evaluation of novel heterocyclic derivatives of combretastatin A-4.

A novel series of combretastatin A-4 heterocyclic analogues was prepared by replacement of the B ring with indole, benzofurane or benzothiophene, attached at the C2 position. These compounds were evaluated for their abilities to inhibit tubulin assembly: derivative cis3b, having a benzothiophene, showed an activity similar to those of colchicine or deoxypodophyllotoxine. The antiproliferative and antimitotic properties of cis3b against keratinocyte cancer cell lines were also evaluated and the intracellular organization of microtubules in the cells after treatment with both stereoisomers of 3b was also determined, using confocal microscopy.

A synthetic peptide derived from the parasite Toxoplasma gondii triggers human dendritic cells' migration.

The migration of DCs is a critical function, enabling information to be carried to where the immunological response occurs. Parasites are known to weaken host immunity by interfering with the functions of DCs and thus, may be a source of molecules with immunomodulatory properties. Here, we demonstrate that the soluble protein, GRA5, specific to Toxoplasma gondii, is able to increase the migration of human CD34-DCs toward CCL19.

Internalisation of hybrid titanium dioxide/para-amino benzoic acid nanoparticles in human dendritic cells did not induce toxicity and changes in their functions.

Nanoparticles (NPs) have been reported to penetrate into human skin through lesional skin or follicular structures. Therefore, their ability to interact with dendritic cell (DC) was investigated using DCs generated from monocytes (mono-DCs). Hybrid titanium dioxide/para-amino benzoic acid (TiO(2)/PABA) NPs did not induce any cell toxicity.

Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France.

The CYP1B1 gene (GenBank: U56438), a member of the cytochrome P450 gene family, has been shown to be mutated in patients with primary congenital glaucoma (PCG), a rare but severely blinding form of glaucoma. Here, we have investigated CYP1B1 mutations in 31 unrelated French PCG patients. Mutations were found in 15 (48%) patients.