title: Development of solid nanoparticles based on hydroxypropyl-β-cyclodextrin aimed for the colonic transmucosal delivery of diclofenac sodium.
abstract: OBJECTIVE
  Nanoparticles were designed for the oral administration and transmucosal colon delivery of drugs.
  
  
  METHODS
  Preparation parameters were studied in order to develop solid pH-dependent drug-release nanoparticles, constituted by hydroxypropyl-β-cyclodextrin and/or Eudragit(®) L100 loaded with diclofenac sodium. Nanoemulsions were prepared by the emulsion-evaporation method using various homogenizers. Different preparative conditions were tested. The emulsions obtained were analysed in terms of size and then dried to obtain solid nanoparticles which were characterized in vitro (particle size, morphology, dissolution, solid state characterization). The effect of nanoparticles on drug permeation through synthetic membranes, colonic pig mucosa and Caco2 cell line were performed. Toxicity studies were carried out to assess the safety of the raw materials used and the nanosystems produced.
  
  
  RESULTS
  Appropriate parameters to obtain nanoemulsions stable enough to be desiccated were determined: Panda NS100L was the most suitable homogenizer for the preparation; particle size ranged between 100 and 600 nm depending on the production method. Solid nanoparticles were obtained by an exsiccation process, which does not modify the mean size. pH-dependent drug-release nanoparticles were obtained. The nanoencapsulation process decreased the crystallinity of the drug. Materials and nanoparticles were highly biocompatible. Transmucosal delivery of drug is dependent on the polymer and the test employed: cyclodextrin improved drug permeation across colonic pig mucosa.
  
  
  CONCLUSIONS
  Formulations containing hydroxypropyl-β-cyclodextrin represent new colon-targeted nanoparticles for transmucosal delivery of drugs.
authors.affiliation: Dipartimento di Scienze del Farmaco, University of Sassari, Via Muroni Dipartimento di Scienze Botaniche, Ecologiche e Geologiche, University of Sassari, Via Piandanna, Sassari Dipartimento di Chimica Farmaceutica, University of Pavia, Via Taramelli, Pavia, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.forename: Gianpiera
authors.initials: G
authors.lastname: Spada
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.forename: Guido
authors.initials: G
authors.lastname: Cerri
authors.forename: Antonio
authors.initials: A
authors.lastname: Brundu
authors.forename: Massimo
authors.initials: M
authors.lastname: Cossu
authors.forename: Milena
authors.initials: M
authors.lastname: Sorrenti
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D058956:Administration, Mucosal; D000818:Animals; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003106:Colon / Q000378:metabolism*; D003460:Crystallization; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000493:pharmacokinetics* / Q000633:toxicity; D004655:Emulsions / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010316:Particle Size; D010539:Permeability; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000633:toxicity; D013552:Swine; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000633:toxicity
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D011109:Polymethacrylic Acids; D047392:beta-Cyclodextrins; D004008:Diclofenac; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C038300:methylmethacrylate-methacrylic acid copolymer