title: Formulation and in vitro evaluation of polymeric enteric nanoparticles as dermal carriers with pH-dependent targeting potential.
abstract: pH-sensitive nanoparticles which release in a controlled fashion on the skin or dissolve in the hair follicle could significantly improve treatment effectiveness and make transfollicular drug delivery a success. Dexamethasone-loaded Eudragit® L 100 nanoparticles were prepared by nanoprecipitation from an organic drug-polymer solution. Their toxicity potential was assessed using isolated human fibroblasts. pH-dependent swelling and erosion kinetics of the nanoparticles were investigated by dynamic light scattering and viscosity measurements and its effect on drug release was assessed in vitro with Franz diffusion cells. Stable, 100-550nm-sized dexamethasone-loaded Eudragit® L 100 nanoparticles with drug loading capacity and entrapment efficiency as high as 8.3% and 85%, respectively, were obtained by using polyvinyl alcohol as a stabilizer and ethanol as organic solvent. The nanoparticles showed little or no toxicity on isolated normal human fibroblasts. Dexamethasone existed in the nanoparticles as solid solution or in amorphous form. The nanoparticles underwent extensive swelling and slow drug release in media with a low buffer capacity (as low as 10mM) and a higher pH or at a pH close to the dissolution pH of the polymer (pH6) and a higher buffer capacity. In 40mM buffer and above pH6.8, the nanoparticles eroded fast or dissolved completely and thus released the drug rapidly. pH-sensitive nanoparticles which potentially release in a controlled manner on the stratum corneum but dissolve in the hair follicle could be prepared.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, D-12169 Berlin, Germany.
authors.forename: Fitsum Feleke
authors.initials: FF
authors.lastname: Sahle
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, D-12169 Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Balzus
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal, D-14558 Potsdam, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gerecke
authors.affiliation: Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, Nuthetal, D-14558 Potsdam, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, D-12169 Berlin, Germany. Electronic address: bodmeier@zedat.fu-berlin.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004339:Drug Compounding; D065546:Drug Liberation; D005347:Fibroblasts / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D005938:Glucocorticoids; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D003907:Dexamethasone
keywords: Acetic acid (PubChem CID: 176); Dexamethasone; Dexamethasone (PubChem CID: 5743); Enteric polymer; Erosion kinetics; Eudragit® L 100; Eudragit® L 100 (PubChem CID: 65358); H2DCFDA (PubChem CID: 77718); MTT (PubChem CID: 64965); Polyvinyl alcohol (PubChem CID: 11199); Potassium dihydrogen phosphate (PubChem CID: 516951); Skin nanocarrier; pH-sensitive nanoparticles