Oral administration is the most commonly used and readily accepted form of drug delivery; however, it is find that many drugs are difficult to attain enough bioavailability when administered via this route. Polymeric micelles (PMs) can overcome some limitations of the oral delivery acting as carriers able to enhance drug absorption, by providing (1) protection of the loaded drug from the harsh environment of the GI tract, (2) release of the drug in a controlled manner at target sites, (3) prolongation of the residence time in the gut by mucoadhesion, and (4) inhibition of efflux pumps to improve the drug accumulation. To explain the mechanisms for enhancement of oral bioavailability, we discussed the special stability of PMs, the controlled release properties of pH-sensitive PMs, the prolongation of residence time with mucoadhesive PMs, and the P-gp inhibitors commonly used in PMs, respectively. The primary purpose of this paper is to illustrate the potential of PMs for delivery of poorly water-soluble drugs with bioavailability being well maintained.

Using guanidine-HCl extraction, acetone precipitation, ultra-filtration and chromatography, a novel polypeptide with potent anti-angiogenic activity was purified from cartilage of the shark, Prionace glauca. N-terminal amino acid sequence analysis and SDS-PAGE revealed that the substance is a novel polypeptide with MW 15500 (PG155). The anti-angiogenic effects of PG155 were evaluated using zebrafish embryos model in vivo. Treatment of the embryos with 20 mg/ml PG155 resulted in a significant reduction in the growth of subintestinal vessels (SIVs). A higher dose resulted in almost complete inhibition of SIV growth, as observed by endogenous alkaline phosphatase (EAP) staining assay. An in vitro transwell experiment revealed that the polypeptide inhibited vascular endothelial growth factor (VEGF) induced migration and tubulogenesis of human umbilical vein endothelial cells (HUVECs). Exposure of HUVECs in 20 mg/ml PG155 significantly decreased the density of migrated cells. Almost complete inhibition of cell migration was found when HUVECs were treated with 40-80 mg/ml PG155. PG155 (20 mg/ml) markedly inhibited the tube formation of HUVECs and a dose-dependent effect was also found when treatment of HUVECs with PG155 at the concentration from 20-160 mg/ml.

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The purpose of this study was to compare the chondroprotective effects of chondroitin sulfate (CS)-hyaluronic acid (HA) (CS-HA) injection and HA injection in an experimental model of osteoarthritis. After induction of osteoarthritis in rabbits, 28 rabbits were randomized into four groups: control group, 'HA' group, 'CS' group, and 'CS-HA' group. After 7 days, rabbits in the control group, 'HA' group, 'CS' group and 'CS-HA' group were respectively treated with normal saline, HA, CS, or CS-HA injection in the knees. All animals were treated once weekly. The animals were treated continuously for 5 weeks. Histological and biochemical evaluations were performed. As shown by histological observation, CS-HA injection treatment showed a chondroprotective effect on osteoarthritis. However, the histological scores of 'HA' group and 'CS-HA' group were not significantly different (p > 0.05). The results of biochemical evaluation showed that the expression levels of IL-1β, TNF-α, TIMP-1 and NO in synovial fluid of treated groups were all different from the control group (p < 0.05). However, the expression levels of these biochemical molecules in three treated groups were not significantly different (p > 0.05). In conclusion, CS-HA injection showed no obvious advantage over HA injection in osteoarthritis treatment.