title: In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of sulpiride.
abstract: OBJECTIVE
  An in-situ forming gel-like depot, prepared by using an appropriate polyaspartamide-polylactide graft copolymer, has been employed to release in a sustained way sulpiride.
  
  
  METHODS
  α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-g-polylactic acid (PHEA-g-PLA) has been used as a polymer component. Its physicochemical properties make possible to dissolve it in N-methyl-2-pyrrolidone, with the obtainment of a solution able to form a gel-like depot once injected into a physiological medium. Cell compatibility of PHEA-g-PLA depot has been investigated, using murine dermal fibroblasts as cell model. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt assay and fluorescence microscopy have been employed to evaluate cell viability and morphology after contact with PHEA-g-PLA depot. Pharmacokinetic parameters of sulpiride released from depot have been determined following subcutaneous administration to rabbits and compared with corresponding parameters following administration of free sulpiride solution.
  
  
  RESULTS
  It has been demonstrated that the system does not affect significantly the viability of fibroblasts and is able to sustain the release of sulpiride until a week, with a burst effect dependent on the initial weight ratio polymer/drug.
  
  
  CONCLUSIONS
  In-vivo release profiles and pharmacokinetic parameters suggest that PHEA-g-PLA depot could have interesting clinical applications for a once a week administration of poorly soluble drugs to humans or animals.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Calogero
authors.initials: C
authors.lastname: Fiorica
authors.forename: Fabio Salvatore
authors.initials: FS
authors.lastname: Palumbo
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pitarresi
authors.forename: Mario
authors.initials: M
authors.lastname: Giorgi
authors.forename: Filippo
authors.initials: F
authors.lastname: Calascibetta
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D010455:Peptides / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000008:administration & dosage* / Q000493:pharmacokinetics*
chemical_list: D010455:Peptides; D011091:Polyesters; D011108:Polymers; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); C033616:poly(lactide); D013469:Sulpiride
keywords: graft copolymers; in-situ forming depot; polylactic acid; sulpiride; α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide