Abstract

 
 
 
 Purpose: To investigate the physicochemical properties and in vitro cytotoxic effect of a potent epidermal growth factor receptor-tyrosine kinase (EGFRWT-TK) inhibitor, 1H-pyrazolo [3,4-d] pyrimidine (FEP) derivative and formulated as solid lipid nanoparticles (SLNs) using stearic acid (ST) or glycerylmonostearate (GMS).
 Methods: The SLNs were prepared by hot homogenization and sonication method. The effect of formulation variables on particle size, zeta potential and polydispersity index (PDI) of SLNs were studied, and an optimized formulation selected. Drug-excipient interactions were assessed by differential scanning calorimetry (DSC) and Fourier Transform Infrared (FTIR). Mammary gland breast cancer (MCF-7) and human colon cancer (HCT116) human cell lines were used to evaluate the cytotoxic activity of the free and FEP-loaded SLNs.
 Results: The particle size of the SLNs was in the range of 138 - 819 nm, while zeta potential varied from -15 to -20 nm. FEP-loaded SLNs exhibited significant cytotoxic effect compared to the free drug and doxorubicin in the two cell lines (p < 0.05). The activity was higher in HCT116 compared with MCF-7 cells (p < 0.007). The concentration of FEP loaded SLNs, free drug and doxorubicin that showed 50 % inhibition (IC50) for breast cancer cells were 1.06 ± 0.09, 2.58 ± 0.16 and 3.75 ± 0.4 μg/ml, respectively.
 Conclusion: The findings show that FEP-loaded SLNs have greater in-vitro cytotoxic activity than the free FEP, and thus, might improve cancer therapy in humans.
 
 
 
Highlights
A new 1H-pyrazolo [3,4-d] pyrimidine derivative has been synthesized, and it showed significant anticancer potential [1]
Its mechanism of action involves the inhibition of epidermal growth factor receptor-tyrosine kinase (EGFR-TK), which have been shown to be over-expressed in many types of tumors, such as breast and hepatic cancers [1]
Combination of GMS and poloxamer 188 resulted in smaller particle size (138 - 249 nm) compared to other preparations (495 - 819 nm)
Summary
A new 1H-pyrazolo [3,4-d] pyrimidine derivative has been synthesized, and it showed significant anticancer potential [1]. FEP showed promising in-vitro cytotoxic effect in EGFR-containing cells, its invivo performance might face a variety of obstacles, such as rapid clearance, poor bioavailability and toxicity of vital organs. All these points were taken into consideration in order to enhance the efficacy of this substance. Two human tumor cell lines namely: mammary gland breast cancer (MCF-7) and colon cancer (HCT116) were obtained from ATCC via Holding company for biological products and vaccines (VACSERA), Cairo, Egypt It was synthesized by the method described in a Gaber et al [1] publication. Significant differences were considered, and assumed at p < 0.05
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