The Impact of Gelatin on the Pharmaceutical Characteristics of Fucoidan Microspheres with Posaconazole.

Fungal infections and invasive mycoses, despite the continuous medicine progress, are an important globally therapeutic problem. Multicompartment dosage formulations (e.g., microparticles) ensure a short drug diffusion way and high surface area of drug release, which as a consequence can provide improvement of therapeutic efficiency compared to the traditional drug dosage forms. As fucoidan is promising component with wide biological activity per se, the aim of this study was to prepare fucospheres (fucoidan microparticles) and fucoidan/gelatin microparticles with posaconazole using the one-step spray-drying technique. Pharmaceutical properties of designed fucospheres and the impact of the gelatin addition on their characteristics were evaluated. An important stage of this research was in vitro evaluation of antifungal activity of developed microparticles using different Candida species. It was observed that gelatin presence in microparticles significantly improved swelling capacity and mucoadhesiveness, and provided a sustained POS release. Furthermore, it was shown that gelatin addition enhanced antifungal activity of microparticles against tested Candida spp. strains. Microparticles formulation GF6, prepared by the spray drying of 20% fucoidan, 5% gelatin and 10% Posaconazole, were characterized by optimal mucoadhesive properties, high drug loading and the most sustained drug release (after 8 h 65.34 ± 4.10% and 33.81 ± 5.58% of posaconazole was dissolved in simulated vaginal fluid pH 4.2 or 0.1 M HCl pH 1.2, respectively).

Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms.

Fucoidan is a polysaccharide built from L-fucose molecules. The main source of this polysaccharide is the extracellular matrix of brown seaweed (Phaeophyta), but it can be also isolated from invertebrates such as sea urchins (Echinoidea) and sea cucumbers (Holothuroidea). Interest in fucoidan is related to its broad biological activity, including possible antioxidant, anti-inflammatory, antifungal, antiviral or antithrombotic effects. The potential application of fucoidan in the pharmaceutical technology is also due to its ionic nature. The negative charge of the molecule results from the presence of sulfate residues in the C-2 and C-4 positions, occasionally in C-3, allowing the formation of complexes with other oppositely charged molecules. Fucoidan is non-toxic, biodegradable and biocompatible compound approved by Food and Drug Administration (FDA) as Generally Recognized As Safe (GRAS) category as food ingredient. Fucoidan plays an important role in the pharmaceutical technology, so in this work aspects concerning its pharmaceutical characteristics and designing of various dosage forms (nanoparticles, liposomes, microparticles, and semisolid formulations) with fucoidan itself and with its combinations with other polymers or components that give a positive charge were reviewed. Advantages and limitations of fucoidan utilization in the pharmaceutical technology were also discussed.

A link between central kynurenine metabolism and bone strength in rats with chronic kidney disease.

BACKGROUND: Disturbances in mineral and bone metabolism represent one of the most complex complications of chronic kidney disease (CKD). Serotonin, a monoamine synthesized from tryptophan, may play a potential role in bone metabolism. Brain-derived serotonin exerts a positive effect on the bone structure by limiting bone resorption and enhancing bone formation. Tryptophan is the precursor not only to the serotonin but also and primarily to kynurenine metabolites. The ultimate aim of the present study was to determine the association between central kynurenine metabolism and biomechanical as well as geometrical properties of bone in the experimental model of the early stage of CKD. METHODS: Thirty-three Wistar rats were randomly divided into two groups (sham-operated and subtotal nephrectomized animals). Three months after surgery, serum samples were obtained for the determination of biochemical parameters, bone turnover biomarkers, and kynurenine pathway metabolites; tibias were collected for bone biomechanical, bone geometrical, and bone mass density analysis; brains were removed and divided into five regions for the determination of kynurenine pathway metabolites. RESULTS: Subtotal nephrectomized rats presented higher serum concentrations of creatinine, urea nitrogen, and parathyroid hormone, and developed hypocalcemia. Several biomechanical and geometrical parameters were significantly elevated in rats with experimentally induced CKD. Subtotal nephrectomized rats presented significantly higher kynurenine concentrations and kynurenine/tryptophan ratio and significantly lower tryptophan levels in all studied parts of the brain. Kynurenine in the frontal cortex and tryptophan in the hypothalamus and striatum correlated positively with the main parameters of bone biomechanics and bone geometry. DISCUSSION: In addition to the complex mineral, hormone, and metabolite changes, intensified central kynurenine turnover may play an important role in the development of bone changes in the course of CKD.