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Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus permeating properties.

Abstract：

:The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the fluoroquinolone antibiotic ciprofloxacin (CIP) exhibiting highly mucus permeating properties and antimicrobial activity in in vitro models. Various SEDDS formulations were developed and evaluated regarding droplet size, polydispersity index, zeta potential and formulation stability. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus, as well as in cystic fibrosis (CF) sputum freshly collected from CF patients using Transwell® setup and single particle tracking (SPT), respectively. In order to evaluate antibacterial activity in an in vitro model against Staphylococcus aureus and other pathogens, minimum inhibitory concentrations (MIC) and time-kill curves were determined. In addition, in vitro release of ciprofloxacin and cytotoxicity studies were conducted. The preselected formulations F1 and F11 exhibited a mean droplet size of 79 nm and 25 nm, respectively, and a negative zeta potential. SEDDS containing CIP exhibit improved ability to permeate porcine intestinal mucus and CF sputum. After 4 h, F1-CIP formulation resulted in a 1.6 - fold and F11-CIP a 2.0 - fold higher amount of permeated ciprofloxacin through the sputum layer with respect to free CIP. Moreover, the antimicrobial activity of F11-CIP against S. aureus was higher than that of free CIP. According to these results, SEDDS formulations should be taken into consideration as promising delivery systems for the treatment of pulmonary infections accompanied by mucus dysfunction.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Zaichik S,Steinbring C,Menzel C,Knabl L,Orth-Höller D,Ellemunter H,Niedermayr K,Bernkop-Schnürch A

doi

10.1016/j.ijpharm.2018.06.005

subject

Has Abstract

pub_date

2018-08-25 00:00:00

pages

282-290

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(18)30396-X

journal_volume

547

pub_type

杂志文章

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