Targeted antitumoral dehydrocrotonin nanoparticles with L-ascorbic acid 6-stearate.
Tumoral cells are known to have a higher ascorbic acid uptake than normal cells. Therefore, the aim of this study was to obtain polymeric nanoparticles containing the antitumoral compound trans-dehydrocrotonin (DHC) functionalized with L-ascorbic acid 6-stearate (AAS) to specifically target this system tumoral cells. Nanoparticle suspensions (NP-AAS-DHC) were prepared by the nanoprecipitation method. The systems were characterized for AAS presence by thin-layer chromatography and for drug loading (81-88%) by UV-Vis spectroscopy. To further characterize these systems, in vitro release kinetics, size distribution (100-140 nm) and Zeta potential by photon-correlation spectroscopic method were used. In vitro toxicity against HL60 cells was evaluated by tetrazolium reduction and Trypan blue exclusion assays. Cell death by apoptosis was quantified and characterized by flow cytometry and caspase activity. Zeta potential analyses showed that the system has a negatively charged outer surface and also indicate that AAS is incorporated on the external surface of the nanoparticles. In vitro release kinetics assay showed that DHC loaded in nanoparticles had sustained release behavior. In vitro toxicity assays showed that NP-AAS-DHC suspension was more effective as an antitumoral than free DHC or NP-DHC and increased apoptosis induction by receptor-mediated pathway.
Frungillo
Lucas
L
Laboratório de Cultura de Células e Biofármacos, Instituto de Biologia, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil.
Martins
Dorival
D
Teixeira
Sérgio
S
Anazetti
Maristela Conti
MC
Melo
Patrícia da Silva
Pda S
Durán
Nelson
N
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000138:chemical synthesis; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002855:Chromatography, Thin Layer; D004396:Coloring Agents; D045785:Diterpenes, Clerodane / Q000008:administration & dosage* / Q000138:chemical synthesis; D016503:Drug Delivery Systems; D004563:Electrochemistry; D005079:Excipients; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D053758:Nanoparticles; D010316:Particle Size; D013056:Spectrophotometry, Ultraviolet; D013535:Suspensions; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D045785:Diterpenes, Clerodane; D005079:Excipients; D013535:Suspensions; D013778:Tetrazolium Salts; D013844:Thiazoles; C103060:dehydrocrotonin; C036225:ascorbyl monostearate; D020169:Caspases; C022616:thiazolyl blue; D014343:Trypan Blue; D001205:Ascorbic Acid