title: Tamoxifen-loaded poly(L-lactide) nanoparticles: Development, characterization and in vitro evaluation of cytotoxicity.
abstract: In this study, poly(L-lactide) (PLA) nanoparticles containing Tamoxifen (Tmx) were developed using an emulsion/solvent evaporation method, observing the influence of surfactants and their concentrations on mean particle size and drug entrapment. Nanoparticles were characterized in terms of size, morphology, polydispersity, interaction drug-polymer and in vitro drug release profile. Cytotoxicity over erythrocytes and tumor cells was assessed. The optimized formulation employed as surfactant 1% polyvinyl alcohol. Mean particle size was 155±4 nm (n=3) and Tmx encapsulation efficiency was 85±8% (n=3). The in vitro release profile revealed a biphasic release pattern diffusion-controlled with approximately 24% of drug released in 24 h followed by a sustained release up to 120 h (30% of Tmx released). PLA nanoparticles containing Tmx presented a very low index of hemolysis (less than 10%), in contrast to free Tmx that was significantly hemolytic. Tmx-loaded PLA nanoparticles showed IC50 value 2-fold higher than free Tmx, but considering the prolonged Tmx release from nanoparticles, cytotoxicity on tumor cells was maintained after nanoencapsulation. Thus, PLA nanoparticles are promising carriers for controlled delivery of Tmx with potential application in cancer treatment.
authors.affiliation: Universidade Estadual do Centro-Oeste/UNICENTRO, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Clescila
authors.initials: C
authors.lastname: Altmeyer
authors.affiliation: Universidade Estadual do Centro-Oeste/UNICENTRO, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Thaysa Ksiaskiewcz
authors.initials: TK
authors.lastname: Karam
authors.affiliation: Universidade Estadual do Centro-Oeste/UNICENTRO, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Najeh Maissar
authors.initials: NM
authors.lastname: Khalil
authors.affiliation: Universidade Estadual do Centro-Oeste/UNICENTRO, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil. Electronic address: rubianamainardes@hotmail.com.
authors.forename: Rubiana Mara
authors.initials: RM
authors.lastname: Mainardes
mesh_terms: D004337:Drug Carriers; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D013629:Tamoxifen / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D011091:Polyesters; D013629:Tamoxifen; C033616:poly(lactide)
keywords: Cytotoxicity; Hemolysis; Nanoparticles; Poly(L-lactide); Tamoxifen