title: Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method.
abstract: BACKGROUND
  Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections.
  
  
  METHODS
  Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity.
  
  
  RESULTS
  The nanoparticles prepared in this study were spherical, with an average particle size of 85-424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug.
  
  
  CONCLUSIONS
  Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.
authors.affiliation: Dental Materials Department, Faculty of Dentistry, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Tahereh Sadat Jafarzadeh
authors.initials: TS
authors.lastname: Kashi
authors.forename: Solmaz
authors.initials: S
authors.lastname: Eskandarion
authors.forename: Mehdi
authors.initials: M
authors.lastname: Esfandyari-Manesh
authors.forename: Seyyed Mahmoud Amin
authors.initials: SM
authors.lastname: Marashi
authors.forename: Nasrin
authors.initials: N
authors.lastname: Samadi
authors.forename: Seyyed Mostafa
authors.initials: SM
authors.lastname: Fatemi
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Atyabi
authors.forename: Saeed
authors.initials: S
authors.lastname: Eshraghi
authors.forename: Rassoul
authors.initials: R
authors.lastname: Dinarvand
mesh_terms: D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004655:Emulsions / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D009821:Oils / Q000737:chemistry; D010316:Particle Size; D015661:Pasteurellaceae / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000900:Anti-Bacterial Agents; D004655:Emulsions; D009821:Oils; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D008911:Minocycline