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Tuan Hiep Tran,1 Thiruganesh Ramasamy,1 Ju Yeon Choi,1 Hanh Thuy Nguyen,1 Thanh Tung Pham,1 Jee-Heon Jeong,1 Sae Kwang Ku,2 Han-Gon Choi,3 Chul Soon Yong,1 Jong Oh Kim11College of Pharmacy, Yeungnam University, Dae-Dong, 2College of Korean Medicine, Daegu Haany University, Gyeongsan, 3College of Pharmacy, Hanyang University, Hanyangdaehak-ro, Sangnok-gu, Ansan,South KoreaAbstract: The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.Keywords: docetaxel, polyaspartic acid, drug delivery systems, antitumor, pH-sensitive

The regional distribution and frequency of the pancreatic endocrine cells in the splenic lobe of grass lizard, Takydromus wolteri, were studied by immunohistochemical (PAP) method using six types of specific mammalian antisera against bovine Sp-1/chromogranin (bCG), serotonin, insulin, glucagon, somatostatin and human pancreatic polypeptide (hPP). The pancreas was subdivided into two regions--islet kike and exocrine regions. The frequency of each immunoreactive (IR) endocrine cells was calculated as mean number/total 100 islet cells and as mean number/total 1,000 cells (including exocrine and endocrine cells) using automated image analysis process. In addition, the percentage of each IR cell was also calculated. All of six endocrine cells were demonstrated. They were dispersed in the whole pancreatic parenchyma between exocrine acinar cells, or they were also observed as islet like clusters. In islet-like regions, bCG-, insulin- and glucagon-IR cells were detected as one or two cell layer cords and they were located between this cell-cords with 14.30+/-5.62, 61.50+/-9.76 and 26.50+/-9.31/100 cells frequencies, respectively. However, somatostatin-IR cells were mainly located in the peripheral parts not in cell-cords with 12.40+/-4.86/100 cells, and no serotonin- and hPP-IR cells were demonstrated. In exocrine regions, all of bCG-, serotonin-, insulin-, glucagon-, somatostatin- and hPP-IR cells were detected and they occurred mainly among the exocrine parenchyma as solitary cells with 10.30+/-2.54, 0.80+/-0.63, 15.50+/-5.30, 5.80+/-2.66, 3.10+/-1.29 and 11.00+/-3.33/1000 cells frequencies, respectively. In addition, serotonin-IR cells were mainly located between epithelia and connective tissue of pancreatic duct. Overall, there were 0.58+/-0.49% serotonin-, 56.44+/-9.35% insulin-, 23.73+/-8.22% glucagon-, 11.28+/-3.03% somatostatin- and 7.97+/-2.02% hPP-IR cells.