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

Date

2017-01-01

Author

Bilecen, Deniz Sezlev
Carlos Rodriguez-Cabello, Jose
Uludag, Hasan
Hasırcı, Vasıf Nejat

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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.

Subject Keywords

Osteoporosis, Targeted delivery, SiRNA, Nanocapsules, PLGA

URI

https://hdl.handle.net/11511/31053

Journal

JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION

DOI

https://doi.org/10.1080/09205063.2017.1354675

Collections

Graduate School of Natural and Applied Sciences, Article

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Citation Formats

D. S. Bilecen, J. Carlos Rodriguez-Cabello, H. Uludag, and V. N. Hasırcı, “Construction of a PLGA based, targeted siRNA delivery system for treatment of osteoporosis,” JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION, pp. 1859–1873, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/31053.