Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins

Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic high density lipoproteins

“…This outcome may be explained as following: first, smaller nanocarrier size and longer half-life in vivo of cP-d-rHDL assisted in their accumulation in the tumors through EPR effect (passive targeting), which were consistent with previous reports (Jie et al, 2012;Lee et al, 2012). Second, SR-BI has been found to be broadly expressed in breast cancer cells, so drug from d-rHDL could be endocytosed into tumors via SR-BImediated mechanism (Cao et al, 2004;Zhang et al, 2013). Third, more apoA-I were conjugated to the lipid bilayer of cP-d-rHDL, thus contributing to striking enhancement in therapeutic efficacy (positive targeting).…”

Plaque-hyaluronidase-responsive high-density-lipoprotein-mimetic nanoparticles for multistage intimal-macrophage-targeted drug delivery and enhanced anti-atherosclerotic therapy

“…Additionally, ST-loaded s-rHDL (ST-s-rHDL) and ST-HA-(E)-PLGA-rHDL formed by the electrostatic absorption between HA and cationic ST-PLGA-rHDL were obtained according to the same methods reported in our previous study, respectively. 10,13 PLGA nanoparticles loaded with ST (ST-PN) was also prepared according to a modified nanoprecipitation technique reported by Zhu et al 34 In vitro characterizations Mean size, zeta potential, ee, and Dl…”

“…10,13 Furthermore, HA-(C)-PLGA-rHDL loaded with ST (ST-HA-(C)-PLGA-rHDL) was synthesized following a modified method as described by Gan et al 33 Ten milligrams of HA was dissolved in 10 mL of water (pH 4.0) overnight to allow complete swelling, and preactivated by 1 M equivalent of coupling agents EDC and NHS for 2 h at 37°C. After the addition of activated HA to ST-PLGA-rHDL solution (1:2, v:v), the reaction continued under stirring for 18 h at 25°C, and the resulting ST-HA-(C)-PLGA-rHDL was separated from free HA and residual reagents by centrifugation (13,000 rpm) for 30 min at 4°C.…”

“…This is due to the fact that the SR-BI is abundant not only in the iMΦ of atherosclerotic lesions but also in the hepatocytes. [10][11][12] To tackle the limited specificity of rHDL for iMΦ, electrostatic adsorption of hyaluronan (HA) on the surface of spherical rHDL (s-rHDL) had been further applied to decrease the undesired uptake by liver and improve the plaque-targeting efficiency of s-rHDL in our previous work, attributing to the weak affinity of HA for hepatic receptors, but high affinity for CD44 receptors overexpressed in the impaired endothelium of atherosclerotic plaque. [13][14][15] Nevertheless, this attempt might still be regarded as a limited success because of the following two drawbacks.…”

Tanshinone II-A: new perspectives for old remedies

“…However, the poor water-solubility, poor intestinal absorption, and low oral bioavailability (about 2.9 --3.4% in rats) [25] have hampered the clinical application of TSN. To overcome these problems, various approaches have been employed, such as the preparation of water-soluble derivative of TSN-sodium tanshinone II-A sulfonate (STS) [4], the preparation of TSN in discoidal and spherical HDL [26], and the development of new drug delivery systems for TSN such as solid dispersion pellets, nanoparticles, and microemulsions [26].…”