title: Poly(lactic acid) nanoparticles loaded with ursolic acid: Characterization and in vitro evaluation of radical scavenging activity and cytotoxicity.
abstract: The purpose of this study was to develop poly(lactic acid) (PLA) nanoparticles containing ursolic acid (UA) by an emulsification-solvent evaporation technique and evaluate the radical scavenging activity over hypochlorous acid (HOCl) and cytotoxicity over erythrocytes and tumor cells. Nanoparticles were successfully obtained and presented mean size of 246nm with spherical or slightly oval morphology, negative zeta potential and 96% of UA encapsulation efficiency. Analyses of FTIR, XRD and DSC-DTG suggest interaction/complexation of UA with PLA matrix and drug amorphization promoted by nanoencapsulation process. Stability study showed that room temperature was the best condition for nanoparticles storage. The in vitro release study showed UA was released from the polymeric matrix over two constants (α, β), suggesting a second order kinetics. After 120h of assay, 60% of UA were released by diffusion. In the HOCl scavenging activity, after 72h of assay UA-loaded nanoparticles presented the same efficacy of free drug. In cytotoxicity test over red blood cells, UA-loaded nanoparticles showed less toxicity on cells than free drug. The cytotoxicity assay over melanoma cells line (B16-F10) showed after 72h that nanoparticles were able to reduce the cell viability in 70%. PLA nanoparticles showed be potential carriers for UA maintaining the antioxidant and antitumor activity of the UA and decreasing its cytotoxicity over normal cells.
authors.affiliation: Universidade Estadual do Centro-Oeste, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Emilli
authors.initials: E
authors.lastname: Antônio
authors.affiliation: Universidade Estadual do Centro-Oeste, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Osmar Dos Reis
authors.initials: ODR
authors.lastname: Antunes
authors.affiliation: Universidade Estadual do Centro-Oeste, Laboratory of Pharmaceutical Nanotechnology, Rua Simeão Camargo Varela de Sá 03, 85040-080 Guarapuava, PR, Brazil.
authors.forename: Isis Souza
authors.initials: IS
authors.lastname: de Araújo
authors.affiliation: Universidade Estadual do Centro-Oeste, 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, 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: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D016166:Free Radical Scavengers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D003692:Delayed-Action Preparations; D016166:Free Radical Scavengers; D011091:Polyesters; D014315:Triterpenes; D000097245:Ursolic Acid; C033616:poly(lactide)
keywords: Cytotoxicity; HOCl; Nanoparticles; Poly(lactic acid); Stability; Ursolic acid