Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells.
Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100 nm and exhibited sustained release of pemetrexed up to 10 h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Ankara University , Ankara , Turkey.
Berrin
B
Küçüktürkmen
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Ankara University , Ankara , Turkey.
Burcu
B
Devrim
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Ankara University , Ankara , Turkey.
Ongun M
OM
Saka
b Foot and Mouth Disease Institute , Ankara , Turkey.
Şükran
Ş
Yilmaz
b Foot and Mouth Disease Institute , Ankara , Turkey.
Taibe
T
Arsoy
a Department of Pharmaceutical Technology, Faculty of Pharmacy , Ankara University , Ankara , Turkey.
Asuman
A
Bozkir
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000068437:Pemetrexed / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D008055:Lipids; D016376:Oligonucleotides, Antisense; D011108:Polymers; D000068437:Pemetrexed
Co-delivery; PLGA; U87MG cells; lipid-polymer hybrid nanoparticles; microRNA-21; pemetrexed