pH-sensitive Eudragit nanoparticles for mucosal drug delivery.
Drug delivery via vaginal epithelium has suffered from lack of stability due to acidic and enzymatic environments. The biocompatible pH-sensitive nanoparticles composed of Eudragit S-100 (ES) were developed to protect loaded compounds from being degraded under the rigorous vaginal conditions and achieve their therapeutically effective concentrations in the mucosal epithelium. ES nanoparticles containing a model compound (sodium fluorescein (FNa) or nile red (NR)) were prepared by the modified quasi-emulsion solvent diffusion method. Loading efficiencies were found to be 26% and 71% for a hydrophilic and a hydrophobic compound, respectively. Both hydrophilic and hydrophobic model drugs remained stable in nanoparticles at acidic pH, whereas they are quickly released from nanoparticles upon exposure at physiological pH. The confocal study revealed that ES nanoparticles were taken up by vaginal cells, followed by pH-responsive drug release, with no cytotoxic activities. The pH-sensitive nanoparticles would be a promising carrier for the vaginal-specific delivery of various therapeutic drugs including microbicides and peptides/proteins.
Division of Pharmaceutical Sciences, University of Missouri, Kansas City, MO 64110, USA.
Jin-Wook
JW
Yoo
Namita
N
Giri
Chi H
CH
Lee
D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019793:Fluorescein / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D010078:Oxazines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000009:adverse effects / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D014621:Vagina / Q000187:drug effects / Q000378:metabolism*
D004337:Drug Carriers; D010078:Oxazines; D004364:Pharmaceutical Preparations; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C044808:nile red; D019793:Fluorescein