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Chen D.,Yantai University | Wang H.,Yantai University | Wang H.,State Key Laboratory of Long Acting and Targeting Drug Delivery System
Journal of Nanoscience and Nanotechnology | Year: 2014

This article reviews the recent developments on novel pH-sensitive ketal-based biodegradable polymeric drug delivery systems. Due to the degradation of ketal derivatives, neutral alcohols and ketones, ketal derivatives can be used to fabricate pH-degradable polymer with pH-degradable ketal linkages in new drug delivery systems by avoiding inflammatory problems. Due to the novelty of ketal polymers, there were few reports about ketal polymers. The review starts with a brief introduction to the pH-sensitive drug delivery system, followed by the structure, preparation and characterization techniques of ketal polymers. Thereafter, the promising applications in various diseases in relation to micro/nano drug carriers based on ketal polymers are summarized and discussed. Copyright © 2014 American Scientific Publishers All rights reserved. Source

Yang S.,Jilin University | Yang X.,Jilin University | Liu Y.,Jilin University | Zheng B.,Jilin University | And 6 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2015

Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation. © 2015 Elsevier B.V. Source

Wang D.,Jilin University | Zhao J.,Jilin University | Liu X.,Jilin University | Sun F.,Jilin University | And 4 more authors.
European Journal of Pharmaceutical Sciences | Year: 2014

Novel biodegradable in situ forming organogel, obtained via the self-assembly of long chain fatty acid in pharmaceutical oil, was prepared and characterized. Different from traditional organogels, the use of organic solvent was avoided in this gel system, in consideration of its tissue irritation. Four kinds of fatty acids were employed as organogelators, which could successfully gel with injectable soybean oil. The gelation procedure was thermo-reversible. Phase transition temperature and time were depended on carbon chain length and concentration of gelators. Optimized formulations containing drug were then injected subcutaneously in rats for pharmacokinetic study. Results showed the steady drug release for one week with the well-controlled burst, which fitted well with the drug release mechanism of both drug diffusion and frame erosion. In vivo imaging of the organogel with fluorescence in live animals suggested that the organogel matrix was gradually absorbed and completely up-taken in nine days. Histopathological analysis of the surrounding tissues was carried out and revealed an overall good biocompatibility property of the implants over drug release period. This research demonstrates that this thermo-sensitive in situ forming organogel system represents a potentially promising platform for sustained drug delivery. © 2014 Elsevier Inc. All rights reserved. Source

Ma P.,Yantai University | Zhang X.,Yantai University | Ni L.,State Key Laboratory of Long Acting and Targeting Drug Delivery System | Li J.,State Key Laboratory of Long Acting and Targeting Drug Delivery System | And 4 more authors.
International Journal of Nanomedicine | Year: 2015

Background: Antibody-dendrimer conjugates have the potential to improve the targeting and release of chemotherapeutic drugs at the tumor site while reducing adverse side effects caused by drug accumulation in healthy tissues. In this study, trastuzumab (TMAB), which binds to human epidermal growth factor receptor 2 (HER2), was used as a targeting agent in a TMAB-polyamidoamine (PAMAM) conjugate carrying paclitaxel (PTX) specifically to cells overexpressing HER2. Methods: TMAB was covalently linked to a PAMAM dendrimer via bifunctional polyethylene glycol (PEG). PTX was conjugated to PAMAM using succinic anhydride as a cross-linker, yielding TMAB-PEG-PAMAM-PTX. Dynamic light scattering and transmission electron microscopy were used to characterize the conjugates. The cellular uptake and in vivo biodistribution were studied by fluorescence microscopy, flow cytometry, and Carestream In Vivo FX, respectively. Results: Nuclear magnetic resonance spectroscopy demonstrated that PEG, PTX, fluorescein isothiocyanate, and cyanine7 were conjugated to PAMAM. Ultraviolet-visible spectroscopy and sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that TMAB was conjugated to PEG-PAMAM. Dynamic light scattering and transmission electron microscopy measurements revealed that the different conjugates ranged in size between 10 and 35 nm and had a spherical shape. In vitro cellular uptake demonstrated that the TMAB-conjugated PAMAM was taken up by HER2-overexpressing BT474 cells more efficiently than MCF-7 cells that expressed lower levels of HER2. Co-localization experiments indicated that TMAB-conjugated PAMAM was located in the cytoplasm. The in vitro cytotoxicity of TMAB-conjugated PAMAM was lower than free PTX due to the slow release of PTX from the conjugate. In vivo targeting further demonstrated that TMAB-conjugated PAMAM accumulated in the BT474 tumor model more efficiently than non-conjugated PAMAM. Conclusion: TMAB can serve as an effective targeting agent, and the TMAB-conjugated PAMAM can be exploited as a potential targeted chemotherapeutic drug delivery system for tumors that overexpress HER2. © 2015 Ma et al. Source

Wang W.-Y.,Yantai University | Wang W.-Y.,State Key Laboratory of Long Acting and Targeting Drug Delivery System | Yao C.,Yantai University | Shao Y.-F.,Yantai University | And 3 more authors.
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

To study pharmacokinetic properties of puerarin poly(amido amine) (PAMAM) dendrimer complex, a sensitive liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated to determine puerarin in rabbit aqueous humor using microdialysis sampling. Astilbin was used as the internal standard. The linear range for puerarin was from 2 to 1000ng/mL (r=0.9986) based on 20μL of aqueous humor. The coefficients of variations for intra-day and inter-day precisions were less than 10.0%, and the relative error of accuracy was within ±6.3%. The mean extraction recovery of puerarin varied from 80.4% to 85.5%. Microdialysis provides a complete concentration versus time profile. A significant difference was observed in main pharmacokinetic parameters of C max, AUC and t 1/2 between puerarin solution and puerarin PAMAM dendrimer complex. Complex formation resulted in an obvious increase in bioavailability of puerarin after topical administration to rabbit according to the above LC-MS/MS assay method. © 2011 Elsevier B.V. Source

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