Synthesis, characterization, and cytotoxicity of doxorubicin-loaded polycaprolactone nanocapsules as controlled anti-hepatocellular carcinoma drug release system

BACKGROUND: Free doxorubicin (Dox) is used as a chemotherapeutic agent against hepatocellular carcinoma (HCC), but it results in cardiotoxicty as a major side effect. Hence, a controlled Dox drug delivery system is extremely demanded. METHODS: Dox was loaded into the non-toxic biodegradable polycaprolactone (PCL) nanocapsules using the double emulsion method. Characterization of Dox-PCL nanocapsules was done using transmission electron microscopy and dynamic light scattering. Encapsulation efficiency and drug loading capacity were quantified using UV–visible spectrophotometry. Drug release was investigated in vitro at both normal (7.4) and cancer (4.8) pHs. Cytotoxicity of Dox-PCL nanocapsules against free Dox was evaluated using the MTT test on normal (Vero) and hepatic cancer (HepG2) cell lines. RESULTS: Spherical nanocapsules (212 ± 2 nm) were succeffully prepared with a zeta potential of (-22.3 ± 2 mv) and a polydisperse index of (0.019 ± 0.01) with a narrow size distribution pattern. The encapsulation efficiency was (73.15 ± 4%) with a drug loading capacity of (16.88 ± 2%). Importantlly, Dox-release from nanocapsules was faster at cancer pH (98%) than at physiological pH (26%). Moreover, although Dox-PCL nanocapsules were less toxic on the normal cell line (GI 50 = 17.99 ± 8.62 µg/ml) than free Dox (GI 50 = 16.53 ± 1.06 µg/ml), the encapsulated Dox showed higher toxic effect on cancer HepG2 cells compared to that caused by the free drug (GI 50 = 2.46 ± 0.49 and 4.22 ± 0.04 µg/ml, respectively). CONCLUSION: The constructed Dox-PCL nanocapsules constitute a potentially controlled anti-HCC therapy with minimal systemic exposure. GRAPHICAL ABSTRACT: [Image: see text]