title: Influence of salt type and ionic strength on self-assembly of dextran sulfate-ciprofloxacin nanoplexes.
abstract: We evaluated an analytical setup to identify optimal preparation conditions for nanoplex formation of small molecule drugs and polyelectrolytes using ciprofloxacin (CIP) and dextran sulfate (DS) as model compounds. The suitability of isothermal titration calorimetry (ITC) as a screening tool for rational formulation optimization was assessed. Besides ITC, static and dynamic light scattering, zeta potential measurements and scanning electron microscopy were applied to analyze the influence of different salt types and ionic strengths on CIP/DS nanoplex formation. The addition of low amounts of salt, especially 0.1M NaCl, improved the formation of CIP/DS nanoplexes. The presence of low amounts of salt led to smaller and more numerous particles of higher uniformity but had no influence on the release of CIP from nanoplexes. Furthermore, the molar range, within which efficient complexation was achieved, was broader in the presence of 0.1M NaCl than in the absence of salt with overall comparable complexation efficiency. Importantly, binding affinity correlated with particle shape and morphology, potentially enabling optimization of critical quality attributes based on ITC data. Altogether, ITC along with supplemental methods is a versatile screening tool for the evaluation of nanoplex formulation conditions regarding mixing ratio, salt type and ionic strength.
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, DE-97074 Würzburg, Germany.
authors.forename: Marika
authors.initials: M
authors.lastname: Kutscher
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, SG-637459, Singapore; Singapore Institute of Technology, 10 Dover Drive, SG-138683, Singapore.
authors.forename: Wean Sin
authors.initials: WS
authors.lastname: Cheow
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, DE-97074 Würzburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Werner
authors.affiliation: Department of General, Visceral, Vascular and Pediatric Surgery, University Clinic of Würzburg, Oberdürrbacher Str. 6, DE-97080 Würzburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Lorenz
authors.affiliation: Institute for Molecular Infection Biology, University of Würzburg, Josef-Schneider-Str. 2, Bau D15, DE-97080 Würzburg, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Ohlsen
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, DE-97074 Würzburg, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Meinel
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, SG-637459, Singapore.
authors.forename: Kunn
authors.initials: K
authors.lastname: Hadinoto
authors.affiliation: Institute for Pharmacy and Food Chemistry, University of Würzburg, Am Hubland, DE-97074 Würzburg, Germany; Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Gründenstrasse 40, CH-4132 Muttenz, Switzerland. Electronic address: oliver.germershaus@fhnw.ch.
authors.forename: Oliver
authors.initials: O
authors.lastname: Germershaus
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002122:Calcium Chloride / Q000737:chemistry; D002151:Calorimetry; D002626:Chemistry, Pharmaceutical; D002939:Ciprofloxacin / Q000737:chemistry*; D016264:Dextran Sulfate / Q000737:chemistry*; D065546:Drug Liberation; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009994:Osmolar Concentration; D011189:Potassium Chloride / Q000737:chemistry; D012965:Sodium Chloride / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D012965:Sodium Chloride; D002939:Ciprofloxacin; D011189:Potassium Chloride; D016264:Dextran Sulfate; D002122:Calcium Chloride
keywords: Ciprofloxacin; Dextran sulfate; Isothermal titration calorimetry; Polyelectrolyte complex