Stealth tanshinone IIA-loaded solid lipid nanoparticles: effects of poloxamer 188 coating on in vitro phagocytosis and in vivo pharmacokinetics in rats / 药学学报

ABSTRACT

Stealth tanshinone IIA-loaded solid lipid nanoparticles (TA-SSLNs) have been prepared and the influence of poloxamer 188 coating on in vitro phagocytosis and in vivo pharmacokinetics in rats were evaluated. TA-SSLNs have been prepared by a nanoprecipitation/solvent diffusion method. Poloxamer 188 was used as a stealth agent. The physicochemical parameters of TA-SSLNs were characterized in terms of particle size, zeta potential, transmission electron microscopy and stability. In vitro, phagocytosis was investigated by incubating TA-SSLNs and non-stealth tanshinone IIA-loaded solid lipid nanoparticles (TA-NSLNs) with murine macrophages. In vivo, pharmacokinetics of TA-SSLNs and TA-NSLNs after a single dose intravenous injection to rat has been studied. The control was tanshinone IIA solution (TA-SOL). The results showed that TA-SSLNs had an average diameter of (91.3 +/- 3.4) nm, zeta potential of (-19.7 +/- 1.6) mV, drug loading of (4.7 +/- 0.5) % and entrapment efficiency of (92.5 +/- 2.1) %. Phagocytosis studies showed significant differences between TA-SSLNs and TA-NSLNs and demonstrated that the poloxamer 188 coating could decrease the macrophage uptake. In vivo experiments showed that the plasma concentration data of TA-SSLNs, TA-NSLNs and TA-SOL were all fitted to a two-compartment model. Areas under curve (AUCs) of TA-NSLNs and TA-SSLNs were 1.28 and 3.70 times than that of TA-SOL, respectively. TA-SSLNs had generated a long circulating time in blood with a mean residence time (MRT) of 5.286 h, compared to 3.051 h of TA-NSLNs and 0.820 h of TA-SOL. Poloxamer 188 modification on solid lipid nanoparticles (SLNs) reduced opsonization by serum proteins and the macrophage uptake. AUC of tanshinone IIA increased as a function of SLNs. In addition, TA-SSLNs exhibited much longer circulation lifetimes for tanshinone IIA than TA-NSLNs. The pharmacokinetic behavior of the incorporated drug can be modified by changing the surface characteristics of SLNs with the use of poloxamer 188.