Co-delivery of pemetrexed and miR-21 antisense oligonucleotide by lipid-polymer hybrid nanoparticles and effects on glioblastoma cells


KÜÇÜKTÜRKMEN B., DEVRİM GÖKBERK B., SAKA O. M., Yilmaz S., Arsoy T., BOZKIR A.

DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, cilt.43, sa.1, ss.12-21, 2017 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 43 Sayı: 1
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1080/03639045.2016.1200069
  • Dergi Adı: DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.12-21
  • Anahtar Kelimeler: Co-delivery, lipid-polymer hybrid nanoparticles, microRNA-21, pemetrexed, PLGA, U87MG cells, CENTRAL-NERVOUS-SYSTEM, BLOOD-BRAIN-BARRIER, ACID) NANOPARTICLES, DRUG-DELIVERY, GENE-THERAPY, IN-VITRO, TEMOZOLOMIDE, TUMOR, ANTI-MIR-21, INHIBITION
  • Ankara Üniversitesi Adresli: Evet

Özet

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.