Cilostazol-loaded solid lipid nanoparticles: Bioavailability and safety evaluation in an animal model

Abstract

Cilostazol (CLZ) is an antiplatelet agent with limited solubility (∼6 μg/ml at 25 °C), poor absorption and low oral bioavailability. In this study, solid lipid nanoparticles (SLNs) were used as a drug delivery system to improve the CLZ dissolution, absorption and bioavailability. Micro-emulsion method was used to fabricate CLZ-loaded SLNs. The SLNs were composed of palmityl alcohol, Tween® 80, and Span® 40 as solid lipid, surfactant, and co-surfactant, respectively. Additionally, Myrj 52 was used as a steric stabiliser. The SLNs were characterised in terms of particle size, zeta potential, polydispersity index (PDI), and incorporation efficiency (IE). Transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and Fourier transform infrared (FTIR) spectroscopy were also performed. In vitro release and pharmacokinetic studies were carried out, followed by evaluation of the safety and stability of the formulated SLNs. Optimised CLZ-loaded SLNs showed a spherical morphology with particle sizes below 200 nm, with excellent PDI (0.18), zeta potential (−29.7 mV), and %IE (92%). FTIR and PXRD studies indicated no chemical interaction between the constituents of the SLNs and the conversion of crystalline form of drug to amorphous form, respectively. CLZ-loaded SLNs demonstrated a significantly enhanced release (p < 0.05) and meaningfully improved bioavailability (p < 0.05) as compared with the CLZ suspension. Histopathological evaluation showed that CLZ-loaded SLNs were nontoxic to the cells lining the intestinal tract. They were found to have a stable shelf life during the three-month evaluation period. Hence, it was concluded that CLZ-loaded SLNs have the potential to improve the oral bioavailability of CLZ without toxicity.