Salt-Driven Deposition of Thermoresponsive Polymer-Coated Metal Nanoparticles on Solid Substrates.

Here we report on a simple, generally applicable method for depositing metal nanoparticles on a wide variety of solid surfaces under all aqueous conditions. Noble-metal nanoparticles obtained by citrate reduction followed by coating with thermoresponsive polymers spontaneously form a monolayer-like structure on a wide variety of substrates in presence of sodium chloride whereas this phenomenon does not occur in salt-free medium. Interestingly, this phenomenon occurs below the cloud point temperature of the polymers and we hypothesize that salt ion-induced screening of electrostatic charges on the nanoparticle surface entropically favors hydrophobic association between the polymer-coated nanoparticles and a hydrophobic substrate.

ß-glucan microparticles targeted to epithelial APN as oral antigen delivery system.

Enteric diseases still have a devastating impact on global health. Oral vaccination is crucial to prevent intestinal infections, since only vaccines delivered to the intestinal tract elicit potent immune responses at the site of pathogen entry. However, oral vaccines encounter multiple barriers, including poor uptake and tolerance mechanisms, preventing the immune system to react to innocuous environmental antigens. Antigen delivery systems combined with selective targeting seem a promising strategy to overcome these obstacles. The current study evaluates the capacity of aminopeptidase N (APN)-targeted ß-glucan microparticles (GPs) as antigen delivery system. Antibodies against APN, an intestinal epithelial receptor, are efficiently oriented conjugated to GPs via the biolinker protein G. The resultant microparticles were analyzed for their antigen load, adjuvanticity and interaction with enterocytes and dendritic cells (DCs). Functionalization of GPs with antibodies neither impedes antigen load nor adjuvanticity. In addition, targeting to APN increases the uptake of microparticles by enterocytes and DCs, leading to an enhanced maturation of the latter as evidenced by an upregulation of maturation markers and a strong pro-inflammatory cytokine response. Finally, oral administration of APN-targeted antigen-loaded particles to piglets elicits higher serum antigen-specific antibody responses as compared to control particles. Taken together, these data support the use of APN-targeted GPs for oral delivery of antigens.

Hydrogen bonded polymeric multilayer films assembled below and above the cloud point temperature.

Polymeric multilayer films assembled via hydrogen-bonding are witnessing increased interest from the scientific community. Here we report on hydrogen bonded multilayers of tannic acid and neutral poly(2-oxazoline)s. Importantly we demonstrate, to the best of our knowledge, for the first time that a temperature responsive polymer, in this case poly(2-(n-propyl)-2-oxazline), can be assembled below and above its TCP with distinctly different growth mechanisms.

Gelucire 44/14 based immediate release formulations for poorly water-soluble drugs.

Here, we aim to evaluate Gelucire 44/14 as non-ionic surface-active excipient to produce immediate-release solid dosage forms for poorly water-soluble drugs. Gelucires are polyethylene glycol (PEG) glycerides composed of mono-, di- and triglycerides and mono- and diesters of PEG. They are inert semi-solid waxy amphiphilic excipients with surface-active properties that spontaneously form a fine dispersion or emulsion upon contact with water. Monolithic Gelucire 44/14 structures are prone to prolonged erosion times, thereby slowing down drug dissolution. To overcome this issue, we combine either granulation or spray-drying, followed by compression into tablets, with an optimized composition of disintegration promoting agents. This formulation strategy allows obtaining nearly 100% drug release within 10 min dissolution time.

Solvent-free drug crystal engineering for drug nano- and micro suspensions.

Poor water-solubility is becoming the leading hurdle for novel drug molecules to reach the market. Enhancing the surface-to-volume ratio by reducing the drug particles size has emerged as a powerful method to enhance the drug dissolution rate of poorly water-soluble drugs. Here we present several approaches to produce micro- and nano-suspensions of febantel and itraconazole, as poorly water-soluble model drugs, in the presence of the self-emulsifying excipient Gelucire 44/14 as additional solubility enhancing agent. Two top-down approaches involving either ball milling or ultrasound treatment, to reduce the size of existing drug crystals, were used as reference processes. Both techniques allowed to significantly reduce the size of the drug crystals and enhance the dissolution of febantel with the ultrasound treated formulation performing the best. In case of itraconazole, no influence of both processing techniques was observed, which is likely to be attributed to it is extremely low water-solubility. To address this challenge, we developed a novel bottom up approach to produce nanosuspensions. This approach involved first dissolving the drug in molten Gelucire 44/14 followed by atomization into cold water. During the atomization, cavitation was induced by ultrasonication. This process yielded milky suspensions in the submicrometer range. Furthermore a fraction of the drug was found to be in amorphous state. Nanosuspensions produced by this technique showed improved dissolution behavior, both in case of febantel and itraconazole.