title: Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.
abstract: Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS.
authors.affiliation: Neuronano Research Center, Department of Experimental Medical Science, Medical Faculty, Lund University, Sweden; Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Sweden. Electronic address: Alexander.Holmkvist@med.lu.se.
authors.forename: Alexander Dontsios
authors.initials: AD
authors.lastname: Holmkvist
authors.affiliation: Neuronano Research Center, Department of Experimental Medical Science, Medical Faculty, Lund University, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Friberg
authors.affiliation: Centre for Analysis and Synthesis, Department of Chemistry, Lund University, Sweden.
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Nilsson
authors.affiliation: Neuronano Research Center, Department of Experimental Medical Science, Medical Faculty, Lund University, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Schouenborg
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D008911:Minocycline / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013386:Succinates / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: C512554:1,4-bis(2-ethylhexyl) sodium sulfosuccinate; D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013386:Succinates; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008911:Minocycline; D002118:Calcium
keywords: AOT (PubChem CID: 23673837); DMAB (PubChem CID: 18669); Drug release; Emulsification-solvent-diffusion method; Hydrophobic ion paring; Minocycline; Minocycline (PubChem CID: 54685925); Nanoparticles; PLGA (PubChem CID: 23111554); Poly(d,l-lactic-co-glycolic acid) (PLGA)