Construction of a PLGA based, targeted siRNA delivery system for treatment of osteoporosis


Bilecen D. S. , Carlos Rodriguez-Cabello J., Uludag H., HASIRCI V. N.

JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, cilt.28, sa.16, ss.1859-1873, 2017 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 28 Konu: 16
  • Basım Tarihi: 2017
  • Doi Numarası: 10.1080/09205063.2017.1354675
  • Dergi Adı: JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
  • Sayfa Sayıları: ss.1859-1873

Özet

Osteoporosis, a systemic skeletal disorder, occurs when bone turnover balance is disrupted. With the identification of the genes involved in the pathogenesis of the disease, studies on development of new treatments has intensified. Shortinterfering RNA (siRNA)is used to knockdown disease related gene expressions. Targeting siRNA in vivo is challenging. The maintenance of therapeutic plasma level is hampered by clearance of siRNA from the body. Targeted systems are useful in increasing the drug concentration at the target site and decreasing side effects. Aim of the present study was to develop an injectable siRNA delivery system toprotect siRNA during systemic distribution and target the siRNA to bone tissue using a thermoresponsive, genetically engineered, elastin-like recombinamer (ELR), designed to interact withthe mineral component of bone. The delivery system consisted of DNAoligo as a siRNA substitute complexed with the cationic polymer, polyethyleneimine (PEI), at N/P ratio of 20. The complex was encapsulated in poly(lactic acid-co-glycolic acid) (PLGA) nanocapsules. PLGA capsules were characterized bySEM, TEM and XPS. FTIR was used to show the preferential attachment of ELR to HAp. Encapsulation efficiency of the complex in PLGA nanocapsules was 48%. The release kinetics of the complex fits the Higuchi release kinetics.