title: Development of Poly(lactide-co-glicolide) Nanoparticles Incorporating Morphine Hydrochloride to Prolong its Circulation in Blood.
abstract: Formulations incorporating nanoparticles (NPs) are widely used to prolong drug release. In this regard, poly(lactide-co-glicolide) (PLGA) is often used in their preparation due to its high degree of biocompatibility and biodegradability. In the present study, morphine HCl is incorporated in PLGA-NPs and different preparation alternatives are evaluated for their effects on the properties, stability and capacity of encapsulation.
  
  
  
  NPs were prepared by a double emulsion solvent diffusion-ammonium loading (DESD-AL) or double emulsion solvent diffusion-traditional (DESD-T) technique. NP morphology, size, zeta potential and encapsulation efficiency were investigated. In vitro studies were performed in phosphate buffer pH 7.4 at 37 ºC and deionized water at 4ºC. Adult male Swiss mice were used to study the pharmacokinetic behavior in vivo.
  
  
  
  Our results show that DESD-AL provides a higher level of morphine entrapment and that increasing the sonication time reduces the size but does not appreciably reduce the entrapment percentage. It was also observed that NP stability was greater when Pluronic F68 was used rather than PVA, and that in vitro assays provided better results with low concentrations of both stabilizers. Lyophilized NPs, after rehydration showed properties that were only slightly different from those of the untreated ones, with no sign of precipitation or aggregation. Finally, the obtained NPs enhanced morphine bioavailability.
  
  
  
  In conclusion, a useful method for encapsulating morphine in order to obtain an extended delivery period is described and its effects are compared with those of the free drug.
authors.forename: Victoria
authors.initials: V
authors.lastname: Gomez-Murcia
authors.affiliation: Departmento de Ingeniería Química, Facultad de Química, Regional Campus of International Excellence Campus Mare Nostrum, Spain.
authors.forename: Mercedes Garcia
authors.initials: MG
authors.lastname: Montalban
authors.affiliation: Departamento de Bioquímica y Biología Molecular A, Universidad de Murcia, Murcia, IMIB-Arrixaca, Regional Campus of International Excellence Campus Mare Nostrum, Facultad de Veterinaria Campus de Espinardo. 30100. Murcia, Spain.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Gomez-Fernandez
authors.affiliation: Departamento de Farmacologia. 0.
authors.forename: Pilar
authors.initials: P
authors.lastname: Almela
mesh_terms: D000818:Animals; D019344:Lactic Acid / Q000097:blood* / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D009022:Morphine Derivatives / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D009022:Morphine Derivatives; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Morphine; PLGA; lyophilized; nanoparticles; pharmacokinetics; poly(lactide-co-glicolide) (PLGA)