Preparation of a Thermosensitive Gel Composed of a mPEG-PLGA-PLL-cRGD Nanodrug Delivery System for Pancreatic Tumor Therapy
Autor: | Baoshan Han, Ying Sun, Ming Shen, Yourong Duan, Yuan-Yuan Xu |
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Rok vydání: | 2015 |
Předmět: |
Materials science
Paclitaxel Polyesters Cell Mice Nude Antineoplastic Agents Peptide Polyethylene glycol Models Biological Fluorescence Polyethylene Glycols chemistry.chemical_compound Drug Delivery Systems Dynamic light scattering In vivo Cell Line Tumor medicine Animals Humans Polylysine General Materials Science chemistry.chemical_classification Temperature Endocytosis Pancreatic Neoplasms Polyester medicine.anatomical_structure chemistry Biochemistry Biophysics Nanoparticles Gels |
Zdroj: | ACS Applied Materials & Interfaces. 7:20530-20537 |
ISSN: | 1944-8252 1944-8244 |
DOI: | 10.1021/acsami.5b06043 |
Popis: | It is hypothesized that a gel (NP-Gel) composed of thermosensitive gel (Gel) and nanoparticles (NP) can prolong drug release time and overcome the drug resistance of pancreatic tumor cells. Paclitaxel (PTX)-loaded monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine)-cyclic peptide (arginine-glycine-aspartic-glutamic-valine acid) (mPEG-PLGA-PLL-cRGD) NP and NP-Gel were designed, optimized, and characterized using dynamic light scattering, transmission electron microscopy, high efficiency liquid chromatography, and rheological analyses. Aspc-1/PTX cell was used in a cell uptake test. A 3D cell model was used to mimic PTX elimination in tissue. The in vivo sustained release and antitumor effects were studied in Aspc-1/PTX-loaded nude mice with xerographic and in situ tumors. The NP were 133.7 ± 28.3 nm with 85.03% entrapped efficiency, 1.612% loaded ratio, and suitable rheological properties. PTX was released as NP from NP-Gel, greatly prolonging the release and elimination times to afford long-term effects. NP-Gel enhanced the uptake of PTX by Aspc-1/PTX cells more than using NP or the Gel alone. Gel and NP-Gel remained solid in the tumor and stayed over 50 days versus the several days of NP in solution. NP-Gel exhibited a much higher inhibition rate in vivo than in solution, NP, or the Gel alone. In conclusion, the antitumor effects of NP-Gel might arise from synergic effects from NP and the Gel. NP primarily reversed drug resistance, while the Gel prolonged release time considerably in situ. This preparation proved effective with a very small PTX dose (250 μg/kg) and exhibited few toxic effects in normal tissue. |
Databáze: | OpenAIRE |
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