PDE5 Inhibitors-Loaded Nanovesicles: Physico-Chemical Properties and In Vitro Antiproliferative Activity.
Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase. Nanoliposomes, made up of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine monohydrate (DPPC), cholesterol, andN-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-mPEG2000) (6:3:1 molar ratio), were characterized by a mean diameter of ~100 nm, a very low polydispersity index (~0.1) and a negative surface charge. The drugs did not influence the physico-chemical properties of the systems and were efficiently retained in the colloidal structure. By using cell count and MTT assay, we found a significant reduction of the viability in both cell lines following 24 h treatment with both nanoliposomal-encapsulated drugs, notably greater than the effect of the free drugs. Our findings demonstrate that nanoliposomes increase the antiproliferative activity of phosphodiesterase-5 inhibitors, providing a useful novel formulation for the treatment of thyroid carcinoma.
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. robertafra87@gmail.com.
Roberta F
RF
De Rose
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. mchiara.cristiano@unicz.it.
Maria Chiara
MC
Cristiano
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. celano.donato@tiscali.it.
Marilena
M
Celano
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. vale.fede1@virgilio.it.
Valentina
V
Maggisano
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. adavero@hotmail.it.
Ada
A
Vero
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. gelombardo@unicz.it.
Giovanni Enrico
GE
Lombardo
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. martina.difrancesco89@gmail.com.
Martina
M
Di Francesco
Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. paolino@unicz.it.
Donatella
D
Paolino
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. d.russo@unicz.it.
Diego
D
Russo
Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, Catanzaro I-88100, Italy. donatocosco@unicz.it.
Donato
D
Cosco
drug delivery systems; human thyroid carcinoma; nanoliposomes; phosphodiesterase-5 (PDE5) inhibitors