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Fan X.,Shandong University | Zhao Y.,Shandong University | Xu W.,Shandong Provincial Qian Foshan Hospital | Li L.,Shandong University
Materials Science and Engineering C | Year: 2016

Dendrimers as a new class of polymeric materials have a highly ordered branched structure, exact molecular weight, multivalency and available internal cavities, which make them extensively used in biology and drug-delivery. Concurrent with the development of dendrimers, much more attention is drawn to a novel block copolymer which combines linear chains with dendritic macromolecules, the linear-dendritic block copolymer (LDBC). Because of the different solubility of the contrasting regions, the amphiphilic LDBCs could self-assemble to form aggregates with special core-shell structures which exhibit excellent properties different from traditional micelles, such as lower critical micelle concentration, prolonged circulation in the bloodstream, better biocompatibility, and lower toxicity. The present review briefly describes the type of LDBC, the self-assembly behavior in solution, and the application in delivery system including the application as drug carriers and gene vectors. The interactions between block copolymers and drugs are also summarized to better understand the release mechanism of drugs from the linear-dendritic block copolymers. © 2016 Elsevier B.V. All rights reserved.

Xu W.,Shandong Provincial Qian Foshan Hospital
International Journal of Molecular Sciences | Year: 2014

Combinations of chemotherapeutic drugs with nucleic acid has shown great promise in cancer therapy. In the present study, paclitaxel (PTX) and DNA were co-loaded in the hyaluronic acid (HA) and folate (FA)-modified liposomes (HA/FA/PPD), to obtain the dual targeting biomimetic nanovector. The prepared HA/FA/PPD exhibited nanosized structure and narrow size distributions (247.4 ± 4.2 nm) with appropriate negative charge of -25.40 ± 2.7 mV. HA/FA/PD (PTX free HA/FA/PPD) showed almost no toxicity on murine malignant melanoma cell line (B16) and human hepatocellular carcinoma cell line (HepG2) (higher than 80% cell viability), demonstrating the safety of the blank nanovector. In comparison with the FA-modified PTX/DNA co-loaded liposomes (FA/PPD), HA/FA/PPD showed significant superiority in protecting the nanoparticles from aggregation in the presence of plasma and degradation by DNase I. Moreover, HA/FA/PPD could also significantly improve the transfection efficiency and cellular internalization rates on B16 cells comparing to that of FA/PPD (p < 0.05) and PPD (p < 0.01), demonstrating the great advantages of dual targeting properties. Furthermore, fluorescence microscope and flow cytometry results showed that PTX and DNA could be effectively co-delivered into the same tumor cell via HA/FA/PPD, contributing to PTX/DNA combination cancer treatment. In conclusion, the obtained HA/FA/PPD in the study could effectively target tumor cells, enhance transfection efficiency and subsequently achieve the co-delivery of PTX and DNA, displaying great potential for optimal combination therapy. © 2014 by the authors.

Yingfang F.,Ocean University of China | Zhuang B.,Ocean University of China | Wang C.,Ocean University of China | Xu X.,Ocean University of China | And 2 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2016

Poor corneal penetration and short residence time on the ocular surface are two major bottlenecks for conventional ophthalmic formulations. To overcome the foregoing dilemmas, we prepared two novel formulations of pimecrolimus nanomicelles (PNM) with particle size of 37.85 ± 1.21. nm and thermosensitive hydrogel (PTH) for treating Keratoconjunctivitis Sicca (KCS). PNM were investigated by transmission electron microscopy (TEM), Malvern laser particle size analyzer, X-ray diffraction (XRD) system, and the content of drug in PNM was measured by high-performance liquid chromatography (HPLC). The drug loading and encapsulation efficiency reached to 7.57% ± 0.10% and 97.9% ± 1.26%, respectively. PTH displayed special gel-sol transition behavior with temperature increasing from 4. °C to 37. °C. The in vitro release profile demonstrated that PNM and PTH exhibited sustained-release behavior compared with free pimecrolimus oil-based eye drop (FPO). In addition, we established a mouse model of KCS induced by benzalkonium chloride to evaluate the therapeutic outcome of different pimecrolimus formulations. The production of tear, fluorescein staining scores and histopathologic examinations of the cornea were assessed in detail. The results confirmed that PNM had the best therapeutic effect among all formulations based on its higher drug encapsulation capability, favourable permeability and sustained release. All these indicated that PNM could serve as a potent ophthalmologic agent for KCS. © 2015 Elsevier B.V.

Wang C.,Ocean University of China | Liu B.,Hong Kong Jockey Club Institute of Chinese Medicine | Xu X.,Ocean University of China | Zhuang B.,Ocean University of China | And 6 more authors.
Oncotarget | Year: 2016

Chemoresistance is the major impediment for treating pancreatic cancer. Herb-derived compound triptolide (TP) can inhibit proliferation of chemo-resistant pancreatic cancer (CPC) cell lines through multiple mechanisms, which exhibited superior anticancer efficacy compared with gemcitabine. However, toxicity due to non-specific exposure to healthy tissues hindered its clinical translation. Herein we successfully achieved targeting CPC cells and avoiding exposure to healthy tissues for TP by nucleolin-specific aptamer (AS1411) mediated polymeric nanocarrier. We conjugated AS1411 aptamer to carboxy terminated poly(ethylene glycol)-block-poly(d, l-lactide) (HOOC-PEG-PDLLA), then prepared AS1411-PEG-PDLLA micelle loading TP (AS-PPT) through solid dispersion technique. AS-PPT showed more antitumor activity than TP and equivalent specific binding ability with gemcitabine-resistant human pancreatic cancer cell (MIA PaCa-2) to AS1411 aptamer in vitro. Furthermore, we studied the distribution of AS-PPT (Cy3-labed TP) at tissue and cellular levels using biophotonic imaging technology. The results showed AS1411 facilitated TP selectively accumulating in tumor tissues and targeting CPC cells. The lifetime of the MIA PaCa-2 cell-bearing mice administrated with AS-PPT was efficiently prolonged than that of the mice subjected to the clinical anticancer drug Gemzar® in vivo. Such work provides a new strategy for overcoming the drug resistance of pancreatic cancer.

Yu H.-H.,Shandong Provincial Qian Foshan Hospital | Mi W.-N.,No. 456 Hospital of the PLA Jinan Military Region | Liu B.,Shandong Provincial Qian Foshan Hospital | Zhao H.-P.,Shandong Provincial Qian Foshan Hospital
Journal of B.U.ON. | Year: 2016

Purpose: Response surface methodology (RSM) using the central composite rotatable design (CCRD) model was used to optimize the formulation of paclitaxel (PTX)-cepharanthine (CEP) nanoparticles for gastric cancer. Methods: Nanoparticles were prepared using nanoprecipitation technique and optimized using central composite rotatable design response surface methodology (CCRD-RSM). Further the optimized nanoparticles were characterised for particle size (PS), zeta potential, entrapment efficiency (EE), drug loading efficiency (DL), anticancer potential against MKN45 (human gastric cancer) cells, in vivo tumor inhibition and survival analysis. Results: Significant findings were the optimal formulation of polymer concentration of 48 mg, surfactant concentration of 45% and EE of 98.12%, DL of 15.61% and mean diameter of 198±4.7 nm. The encapsulation of PTX/CEP into nanoparticles retained the synergistic anticancer efficiency against MKN45 cells. In the in vivo evaluation, PTX/CEP nanoparticles delivered into mice by intravenous injection significantly improved the antitumor efficacy of PTX/CEP. Moreover, PTX/CEP co-loaded nanoparticles substantially increased the overall survival in an established MKN45-transplanted mouse model. Conclusion: These data are the first to demonstrate that PTX/CEP co-loaded nanoparticles increased the anticancer efficacy in cell lines and xenograft mouse model. Our results suggest that PTX/CEP coloaded nanoparticles could be a potential useful chemotherapeutic formulation for gastric cancer.

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