摘要：In order to enhance the targeted delivery of anticancer drugs by polymeric micelles, folic acid(FA), the ligand of folate receptor(FR) over-expressed in the most cancer cells, modified p H-sensitive polymeric micelles were designed and fabricated to encapsulate doxorubicin(DOX) by combination of p H-sensitive amphiphilic polymer poly(2-ethyl-2-oxazoline)-poly(D,L-lactide) with FA-conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide). The prepared micelles were characterized to have about 36 nm in diameter with narrow distribution, well-defined spherical shape observed under TEM and p H-responsive drug release behavior. Moreover, the tumor targeting ability of the FA-modified p H-sensitive polymeric micelles was demonstrated by the cellular uptake, in vitro cytotoxicity to FR-positive KB cells and in vivo real time near-infrared fluorescence imaging in KB tumor-bearing nude mice. The efficient drug delivery by the micelles was ascribed to the synergistic effects of FR-mediated targeting and p H-triggered drug release. In conclusion, the designed FR-targeted p H-sensitive polymeric micelles might be of great potential in tumor targeted delivery of water-insoluble anticancer drugs.

摘要：To overcome the main barrier of intestinal epithelium for the oral absorption of poorly water-soluble drugs and further improve their oral absorption, Gly-Sar, the substrate of the oligopeptide transporter PepT1 widely distributed in the small intestine,conjugated poly(ethylene glycol)-block-poly(D,L-lactide)(Gly-Sar-PEG-b-PLA) was designed and synthesized, and Pep T1-targeted polymeric micelles were prepared and characterized. The structure of the synthesized Gly-Sar-PEG-b-PLA was confirmed by use of TLC and 1 H-NMR. The average molecular weight measured by GPC was 5954 g/mol with PDI of 1.34. The DiI-loaded polymeric micelles from Gly-Sar-PEG-b-PLA with drug loading content of 0.076% were characterized to exhibit 40.36 nm in diameter with PDI of 0.294, and well-defined spherical shape observed by TEM. Furthermore, the PepT1-targeted polymeric micelles profoundly enhanced intestinal absorption of poorly water-soluble drug. Therefore, the designed PepT1-targeted polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

摘要：In the present study, we designed and fabricated pH-sensitive polymeric micelles based on the conjugate of poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（PEOz-PLA） with doxorubicin（PEOz-PLA-imi-DOX） to efficiently inhibit tumor cell growth. Hence, PEOz-PLA-imi-DOX was successfully synthesized by connecting DOX to the hydrophobic end of pH-sensitive PEOz-PLA via acid cleavable benzoic imine linker and characterized by 1 H NMR spectrum and thin layer chromatography. The critical micelle concentration of PEOz-PLA-imi-DOX was determined to be（14.84±3.85） mg/L. The conjugate micelles（denoted as PP-DOX-PM） formed by PEOz-PLA-imi-DOX using film-hydration method were characterized to have a nano-scaled size of about 21 nm in diameter, and the drug loading content was 1.67%. PP-DOX-PM showed pH-dependent drug release behavior with gradually accelerated release of DOX with decrease of pH value, illustrating the micelles＇ distinguishing feature of endo/lysosomal pH from physiological pH by accelerating drug release. As anticipated, PP-DOX-PM maintained the cytotoxicity of DOX against MDA-MB-231 cells. Collectively, PP-DOX-PM might have great potential for effective suppression of tumor growth.

摘要：The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2（OCTN2） were constructed by combining carnitine conjugated poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（Car-PEOz-PLA） with monomethoxy poly（ethylene glycol）-poly（D,L-lactide）（mP EG-PLA）. The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.

摘要：Oral administration is the best way for the most patients due to the good compliance,and intestinal epithelium is the main barrier of oral drug *** order to overcome the small intestine epithelial barrier to orally deliver water-insoluble drugs,deoxycholic acid(DA),a substrate of the intestinal bile acid transporters,conjugated poly(2-ethyl-2-oxazoline)-poly(D,L-lactide)(DA-PEOz-PLA)was designed and synthesized,and deoxycholic acid-modified polymeric micelles composed of DA-PEOz-PLA and mPEG-PLA were fabricated to encapsulate model drug coumarin 6(C6)based on intestinal bile acid *** structure of DA-PEOz-PLA was confirmed using 1 H NMR and TLC,and the molecular weight measured by GPC was 10034 g/mol with a PDI of *** C6-loaded polymeric micelles with drug loading content of 0.085%were characterized to have 40.11 nm in diameter and uniform spherical morphology observed by ***,the deoxycholic acid-modified polymeric micelles were demonstrated to further enhance the transmembrane transport *** mechanic study evidenced that anchorage of deoxycholic acid onto the micelles surface enriched their transcellular transport ***,the designed deoxycholic acid-modified polymeric micelles might have a promising potential for oral delivery of water-insoluble drugs.

摘要：CSP(concentrated solar power)系统通过聚焦太阳光进行光热发电,主要工作介质包括导热油及熔盐。由于太阳能的不连续性,为了提供更稳定的能量输出,发展出了采用熔盐为储热工质进行蓄热的系统,该系统同时也提供了与其它能源系统耦合的可行性。该系统的熔盐回路主要由3个部分构成,分别为集热器、高低温储热罐和蒸汽发生器。通过对50 MW塔式太阳能的热发电系统熔盐回路的各个组件的模型进行建立,设计一套与之相应的控制系统,并针对不同工况下,各个组件及整个系统的响应进行了模拟,得出熔盐回路的瞬态响应特性。由于其熔盐回路与熔盐反应堆具有一定的相似性,本研究也可为熔盐反应堆核能综合利用中储能系统提供参考。