PEGylated-PLGA Nanoparticles Coated with pH-Responsive Tannic Acid–Fe(III) Complexes for Reduced Premature Doxorubicin Release and Enhanced Targeting in Breast Cancer
| Autor: | X. Y. Ma, Fuzheng Ren, Wei Guo, Jiandu Lei, Ruihuan Zhang, Fengzhi Hu, Xiujuan He, Wenyun Zheng, Hu Fabiao, Ting Yan |
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| Rok vydání: | 2020 |
| Předmět: |
Drug Compounding
Pharmaceutical Science Nanoparticle Breast Neoplasms macromolecular substances 02 engineering and technology Pharmacology Ferric Compounds 030226 pharmacology & pharmacy Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Polylactic Acid-Polyglycolic Acid Copolymer Cell Line Tumor Drug Discovery Tannic acid medicine Animals Humans Doxorubicin Cytotoxicity Adverse effect Chemistry technology industry and agriculture Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Disease Models Animal Drug Liberation PLGA Permeability (electromagnetism) Systemic administration Molecular Medicine Female Drug Screening Assays Antitumor Nanoparticle Drug Delivery System 0210 nano-technology Tannins medicine.drug |
| Zdroj: | Molecular Pharmaceutics. 18:2161-2173 |
| ISSN: | 1543-8392 1543-8384 |
| Popis: | Biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as delivery vehicles for chemotherapy drugs. However, premature drug release in PLGA NPs can damage healthy tissue and cause serious adverse effects during systemic administration. Here, we report a tannic acid-Fe(III) (FeIII-TA) complex-modified PLGA nanoparticle platform (DOX-TPLGA NPs) for the tumor-targeted delivery of doxorubicin (DOX). A PEGylated-PLGA inner core and FeIII-TA complex outer shell were simultaneously introduced to reduce premature drug release in blood circulation and increase pH-triggered drug release in tumor tissue. Compared to the unmodified NPs, the initial burst rate of DOX-TPLGA NPs was significantly reduced by nearly 2-fold at pH 7.4. Moreover, the cumulative drug release rate at pH 5.0 was 40% greater than that at pH 7.4 due to the pH-response of the FeIII-TA complex. Cellular studies revealed that the TPLGA NPs had enhanced drug uptake and superior cytotoxicity of breast cancer cells in comparison to free DOX. Additionally, the DOX-TPLGA NPs efficiently accumulated in the tumor site of 4T1-bearing nude mice due to the enhanced permeability and retention (EPR) effect and reached a tumor inhibition rate of 85.53 ± 8.77% (1.31-fold versus DOX-PLGA NPs and 3.12-fold versus free DOX). Consequently, the novel TPLGA NPs represent a promising delivery platform to enhance the safety and efficacy of chemotherapy drugs. |
| Databáze: | OpenAIRE |
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