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Drug Delivery Letters

Author(s): Abdelrahman Y. Sherif*, Gamaleldin I. Harisa and Fars K. Alanazi

DOI: 10.2174/2210303113666221226092547

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SLN Mediate Active Delivery of Gefitinib into A549 Cell Line: Optimization, Biosafety and Cytotoxicity Studies

Page: [133 - 150] Pages: 18

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Abstract

Background: Conventional administration of chemotherapeutic agents associated with low drug distribution to cancer cells with multiple systemic toxicities. Thus, enhancing the active delivery of chemotherapeutic agents to cancer cells increases drug distribution and internalization to targeted cells with minimal systemic toxicities.

Objective and Aim: The current study was designed to prepare and optimize solid lipid nanoparticles (SLN) containing stearic acid (SA) that mediate active delivery and uptake of gefitinib (GEF) to cancer cells.

Methods: The stability of the prepared Plain-SLN formulations was characterized for 90 days. The most stable formulations were loaded with GEF (GEF-SLN) and subjected to pharmaceutical characterization. In vitro dissolution of GEF-SLN formulations was studied using the dialysis method. Biosafety in the terms of hemocompatibility was investigated using fresh blood samples. Additionally, the cytotoxicity of GEF-SLN was examined against the lung cancer cell line (A549).

Results: The obtained results showed that the prepared formulations fall in the nanosize range from 114 to 411 nm with a negative zeta-potential value from -17 to -27 mV. The particle size of Plain- SLN formulations was increased when the GEF is incorporated during preparation. Besides, the crystallinity of SA was disordered following the incorporation of GEF. In addition, GEF entrapment efficiency into SLN was 88% with a sustained-release profile of about 75% in 24 h. Additionally, the present results revealed that using surfactants with high drug solubility negatively impacts the stability of SLN formulation. Furthermore, hemocompatibility results revealed that all SLN formulations showed insignificant hemolysis (1- 4%) at all concentrations. Moreover, cytotoxicity examinations revealed that SLN enhanced the antiprofilated activity of GEF compared to free GEF.

Conclusion: These data concluded that SLN is a hopeful approach to enhancing the selective deposition of GEF into cancer cells and reducing the lymphatic metastasis of lung cancer.

Graphical Abstract

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