Electrospinning scale-up and formulation development of PVA nanofibers aiming oral delivery of biopharmaceuticals

Electrospinning is a promising drying technology providing a rapid and gentle drying at ambient temperature, thus electrospinning of polyvinyl alcohol aqueous solutions was investigated for the solid formulation of biopharmaceuticals. The commonly used single-needle electrospinning does not have adequate productivity to satisfy the industrial requirements, therefore our aim was to study the scale-up of the technology by using high-speed electrospinning. High molecular weight polyethylene oxide as a secondary polymer was applied to enhance the fiber formation of polyvinyl alcohol. While polyvinyl alcohol-polyethylene oxide formulations resulted in adequate fiber formation it was not possible to process them further as the friability of the fibers was too low. In order to increase the friability, the effect of adding various sugars (mannitol, glucose, lactose, saccharose, and trehalose) was investigated. The results showed that mannitol was the best friability enhancing excipient because of its crystallinity and low moisture content in the fibrous sample. In contrast, glucose, lactose, saccharose, and trehalose were amorphous with higher moisture content and fibers containing these were grindable only after post-drying

On the number of solutions of binomial Thue inequalities

Let a, b and n be positive integers with n ≥ 3 and consider the binomial Thue inequality |axn − byn| ≤ 3. In this paper, we extend a result of the first author and prove that, apart from finitely many explicitly given exceptions, this inequality has at most a single solution in positive integers x and y. In the proof, we combine lower bounds for linear forms in logarithms of algebraic numbers with the hypergeometric method of Thue-Siegel and an assortment of techniques from computational Diophantine approximation

The selective PAC1 receptor agonist maxadilan inhibits neurogenic vasodilation and edema formation in the mouse skin

We have earlier shown that PACAP-38 decreases neurogenic inflammation. However, there were no data on its receptorial mechanism and the involvement of its PAC1 and VPAC1/2 receptors (PAC1R, VPAC1/2R) in this inhibitory effect. Neurogenic inflammation in the mouse ear was induced by topical application of the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor activator mustard oil (MO). Consequent neurogenic edema, vasodilation and plasma leakage were assessed by measuring ear thickness with engineer's micrometer, detecting tissue perfusion by laser Doppler scanning and Evans blue or indocyanine green extravasation by intravital videomicroscopy or fluorescence imaging, respectively. Myeloperoxidase activity, an indicator of neutrophil infiltration, was measured from the ear homogenates with spectrophotometry. The selective PAC1R agonist maxadilan, the VPAC1/2R agonist vasoactive intestinal polypeptide (VIP) or the vehicle were administered i.p. 15 min before MO. Substance P (SP) concentration of the ear was assessed by radioimmunoassay. Maxadilan significantly diminished MO-induced neurogenic edema, increase of vascular permeability and vasodilation. These inhibitory effects of maxadilan may be partially due to the decreased substance P (SP) levels. In contrast, inhibitory effect of VIP on ear swelling was moderate, without any effect on MO-induced plasma leakage or SP release, however, activation of VPAC1/2R inhibited the increased microcirculation caused by the early arteriolar vasodilation. Neither the PAC1R, nor the VPAC1/2R agonist influenced the MO-evoked increase in tissue myeloperoxidase activity. These results clearly show that PAC1R activation inhibits acute neurogenic arterial vasodilation and plasma protein leakage from the venules, while VPAC1/2R stimulation is only involved in the attenuation of vasodilation