title: Counter-ion complexes for enhanced drug loading in nanocarriers: Proof-of-concept and beyond.
abstract: Enhanced drug loading is an important prerequisite of nanomedicines, to reach administration dose while reducing the amount of excipient. Considering biocompatible and biodegradable polymers such as PLGA, pH dependent solubility characteristics along with limited organic solvent solubility of the drug hampers nanoparticle (NP) preparation. To improve loading of such molecules, a method based on using counter ions for complex formation is proposed. Formed complex alters the intrinsic solubility of active substance via electrostatic interaction without chemical modification. A proof-of-concept study was conducted with sodium dodecyl sulfate as counter-ion to fluoroquinolone antibiotic ciprofloxacin. Complex formation resulted in suppressed pH dependent solubility over pH 1.2-9.0 and an additional -80 fold increase in organic solubility was achieved. In consequence, NPs prepared by microjet reactor technology have shown enhanced drug loading efficiencies (-78%) and drug loading of 14%. Moreover, the counter-ion concept was also demonstrated with another class of antibiotics, water soluble aminoglycosides gentamycin and tobramycin. In addition, the counter ion was substituted by degradable excipients such as phosphatidic acid derivatives. Successful implementation has proven the counter-ion concept to be a platform concept that can be successfully implemented for a variety of active substances and counter-ions to enhance drug loading in nanocarriers.
authors: MJR PharmJet GmbH, Industriestr. 1B, 66802 Überherrn, Germany; Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany.
authors: Nazende
authors: N
authors: Günday Türeli
authors: MJR PharmJet GmbH, Industriestr. 1B, 66802 Überherrn, Germany.
authors: Akif E
authors: AE
authors: Türeli
authors: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, Saarland University, 66123 Saarbrücken, Germany. Electronic address: Marc.Schneider@mx.uni-saarland.de.
authors: Marc
authors: M
authors: Schneider
mesh_terms: D002939:Ciprofloxacin / Q000008:administration & dosage / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D065546:Drug Liberation; D007477:Ions; D019344:Lactic Acid / Q000008:administration & dosage / Q000378:metabolism*; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000378:metabolism*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011550:Pseudomonas aeruginosa / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D007477:Ions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002939:Ciprofloxacin
keywords: 1,2-Dipalmitoyl-sn-glycero-3-phosphatidic acid, sodium salt (PubChem CID: 643979); Acetonitrile (PubChem CID: 6342); Ciprofloxacin (PubChem CID: 2764); Counter-ion; Dimethyl sulfoxide (PubChem CID: 679); Enhanced encapsulation; Gentamicin (PubChem CID: 3467); Ion complex; Nanomedicine; Pluronic(®) F68 (PubChem CID: 24751); Poly(dl-lactide-co-glycolide) (PubChem CID: 71391); Tobramycin (PubChem CID: 36294); sodium dodecyl sulfate (PubChem CID: 3423265)