Development of particulate drug formulation against C. parvum: Formulation, characterization and in vivo efficacy

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• 作者：Estefaní ; a Blanco-Garcí ; a^a ; Florentina Guerrero-Callejas^b ; José ; Blanco-Mé ; ndez^a ; Hipó ; lito Gó ; mez-Couso^c ; Asteria Luzardo-Á ; lvarez^a ; ^{asteriam.luzardo@usc.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：MS ; microspheres ; CHI ; chitosan ; PVA ; poly(vinyl alcohol) ; GTA ; glutaraldehyde ; DF ; diloxanide furoate ; FITC ; fluorescein isothiocyanate ; β-CD ; β-cyclodextrin ; DM-β-CD ; (2 ; 6-di-O-methyl)-β-cyclodextrin ; C. parvum ; Cryptosporidium parvum ; SEM ; scanning electron microscopy ; TEM ; transmission electron microscopy
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2016
• 出版时间：20 September 2016
• 年：2016
• 卷：92
• 期：Complete
• 页码：74-85
• 全文大小：1325 K

文摘

This research aims towards developing an alternative therapy against Cryptosporidium parvum using bioadhesive paromomycin and diloxanide furoate-loaded microspheres. Microspheres were prepared using chitosan and poly(vinyl alcohol) and two types of cyclodextrins (β-CD and DM-β-CD) for the potential use of treating cryptosporidiosis. This pathogen is associated with gastrointestinal illness in humans and animals. Microparticle formulations were characterized in terms of size, surface charge, drug release and morphology. In vivo bioadhesion properties of CHI/PVA microspheres were also evaluated in mice. Finally, the in vivo efficacy of CHI/PVA microspheres against C. parvum was tested in neonatal mouse model. In this work, microspheres prepared by spray-drying showed spherical shape, diameters between 6.67 ± 0.11 and 18.78 ± 0.07 μm and positively surface charged. The bioadhesion studies demonstrated that MS remained attached at + 16 h (post-infection) to the intestinal cells as detected by fluorescence. This finding was crucial taking use of the fact that the parasite multiplication occurs between 16 and 20 h post-infection. The efficacy of treatment was determined by calculating the number of oocysts recovered from the intestinal tract of mice after 7 days of post-infection. Mice receiving orally administered microspheres with and without drug exhibited significantly lower parasite loads compared with the control mice. Ultrastructural observations by TEM bring to light the uptake of smallest particles by enterocytes associated with conspicuous changes in enterocytic cells. Completely recovery of cell morphology was detected after 24 h of first inoculation with MS. CHI/PVA microspheres appear to be a safe and simple system to be used in an anticryptosporidial treatment. The distinctive features of neonatal mice requires further work to determine the suppressive effect of this particulate delivery system on C. parvum attachment in other animal models.