Abstract
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, and N-(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.
Highlights
The prevalence of thyroid carcinomas is increasing worldwide [1,2]
The DLS analysis evidenced a mean diameter of the empty vesicles of about 100 nm, a homogeneous size distribution and a surface charge of ~ ́20 mV, confirming the data previously reported by our research team [16] (Table 1)
The encapsulation of SIL did not induce a dramatic change in the mean sizes while the lipophilic TAD favored a slight increase in the colloidal diameter and of the polydispersity index (PDI) value
Summary
While the majority of these tumors are well differentiated and may be efficaciously managed by using the radioiodine treatment after surgery, there is a minority of less-differentiated carcinomas which do not respond to the standard treatment [3,4,5]. This behavior is aggressive and is owed to the oncogenic activation of Nanomaterials 2016, 6, 92; doi:10.3390/nano6050092 www.mdpi.com/journal/nanomaterials. We have recently demonstrated the overexpression of phosphodiesterase-5 (PDE5) that occurs, the enzyme which regulates the intracellular levels of cGMP, in a series of thyroid carcinomas; the inhibition of PDE5 by sildenafil (SIL) or tadalafil (TAD) determined a block in the proliferation of thyroid cancer cells in culture, suggesting that specific inhibitors of PDE5 may be proposed for the treatment of these tumors [10].
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