title: Nanoparticle formulation may affect the stabilization of an antiischemic prodrug.
abstract: The prodrug 5'-octanoyl-CPA (Oct-CPA) of the antiischemic N6-cyclopentyladenosine (CPA) has been encapsulated by nanoprecipitation in poly(lactic acid) nanoparticles, which have been recovered by gel-filtration, ultra-centrifugation or dialysis. We have analysed how different surfactants and purification methods can influence the nanoparticle characteristics. The particle sizes have been obtained by scanning electron microscope, whereas a SdFFF system was employed to detect their distributions. The Oct-CPA release from nanoparticles and stabilities in human blood of free and encapsulated prodrug have been analysed by HPLC techniques. The effects of nanoparticles on CPA interaction toward adenosine A1 receptor (its action site) have been analysed using radiolabelled drugs. The smallest nanoparticles and the best degree of homogeneity have been obtained using sodium cholate; the best recovery has been achieved by dialysis, whereas gel-filtration and ultra-centrifugation have induced the greatest removal of surfactants. The release of Oct-CPA was better controlled from the nanoparticles obtained using Pluronic F68 and purified by gel-filtration or ultra-centrifugation. Similarly, these nanoparticles better increased the stability of the prodrug in human blood. In particular, the nanoparticles purified by ultra-centrifugation induced a strong stability to a fraction of the encapsulated Oct-CPA. Any interference by unloaded nanoparticles has been registered for CPA-adenosine A1 receptor interaction.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Modena and Reggio Emilia University, via G. Campi 183, I-41100 Modena, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Leo
authors.forename: C
authors.initials: C
authors.lastname: Contado
authors.forename: F
authors.initials: F
authors.lastname: Bortolotti
authors.forename: B
authors.initials: B
authors.lastname: Pavan
authors.forename: A
authors.initials: A
authors.lastname: Scatturin
authors.forename: G
authors.initials: G
authors.lastname: Tosi
authors.forename: S
authors.initials: S
authors.lastname: Manfredini
authors.forename: A
authors.initials: A
authors.lastname: Angusti
authors.forename: A
authors.initials: A
authors.lastname: Dalpiaz
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D058907:Adenosine A1 Receptor Agonists; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D007511:Ischemia / Q000188:drug therapy*; D049329:Nanostructures; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D020358:Sodium Cholate / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D058907:Adenosine A1 Receptor Agonists; D004337:Drug Carriers; D011355:Prodrugs; D043682:Receptor, Adenosine A1; D013501:Surface-Active Agents; D020442:Poloxamer; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D020358:Sodium Cholate