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Oleanolic acid-loaded PLGA-TPGS nanoparticles combined with heparin sodium-loaded PLGA-TPGS nanoparticles for enhancing chemotherapy to liver cancer
- Source :
- Life sciences. 165
- Publication Year :
- 2016
-
Abstract
- Aim Heparin sodium (HS)-loaded polylactic- co -glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (HPTNs) were prepared as sustained and targeted delivery carriers and combined with oleanolic acid (OA)-loaded PLGA-TPGS nanoparticles (OPTNs) that had been investigated in our previous work to form a combination therapy system for the treatment of liver cancer. Main methods To inspect cellular uptake and evaluate liver-targeting performance by analysing drug concentrations and cryosections, fluorescent probe coumarin-6 and eosin was used in preparations of HS/eosin-loaded, HS/coumarin-6-loaded, and OA/coumarin-6-loaded PLGA-TPGS nanoparticles. All of these NPs were characterized in terms of size, size distribution, surface charge, drug loading, encapsulation efficiency, and in vitro release profile. The apoptosis of HepG2 cells induced by OPTNs combined with HPTNs was determined by Annexin V-FITC staining and PI labelling. Key findings Transmission electron microscopy indicated that all of the nanoparticles were stably dispersed spheres with diameters ranging from 100 to 200 nm. The results demonstrated that fluorescent nanoparticles were efficiently internalized into HepG2 and HCa-F cells, and that they exhibited enhanced liver targeting. The combination of HPTNs and OPTNs resulted in effective cell inhibition in vitro and a remarkable synergistic anticancer effect in vivo . The cell apoptosis results indicated that OPTNs combined with HPTNs could induce HepG2 cell apoptosis and exert synergistic effects. In vivo pharmacodynamics analysis using a solid tumour-bearing mouse model indicated that OPTNs combined with HPTNs could suppress tumour growth by 67.61%. Significance This research suggests that the combined therapy system of OPTNs and HPTNs could be a new means of hepatoma therapy.
- Subjects :
- Stereochemistry
Antineoplastic Agents
02 engineering and technology
Polyethylene glycol
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Polylactic Acid-Polyglycolic Acid Copolymer
In vivo
Annexin
Animals
Humans
Vitamin E
Lactic Acid
General Pharmacology, Toxicology and Pharmaceutics
Oleanolic Acid
Oleanolic acid
Eosin
Chemistry
Heparin
Liver Neoplasms
General Medicine
Hep G2 Cells
021001 nanoscience & nanotechnology
In vitro
PLGA
Apoptosis
030220 oncology & carcinogenesis
Biophysics
Nanoparticles
0210 nano-technology
Polyglycolic Acid
Subjects
Details
- ISSN :
- 18790631
- Volume :
- 165
- Database :
- OpenAIRE
- Journal :
- Life sciences
- Accession number :
- edsair.doi.dedup.....7c7dee8a2964a878f87528f6a1402b44