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

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


Development of PEI-RANK siRNA Complex Loaded PLGA Nanocapsules for the Treatment of Osteoporosis
Bilecen, Deniz Sezlev; Uludag, Hasan; Hasırcı, Vasıf Nejat (2018-04-30)
Osteoporosis, which is characterized by low bone mineral density and susceptibility to fracture, is caused by increased osteoclastic activity. Receptor activator of nuclear factor kappa B ligand (RANKL)/RANK signaling plays an important role in osteoclast differentiation and activation. The current treatment strategies for osteoporosis do not directly address this underlying cause and generates undesired side effects. This led to emergence of controlled delivery systems to increase drug bioavailability and ...
Development of a siRNA delivery system for the treatment of osteoporosis
Sezlev Bilecen, Deniz; Hasırcı, Vasıf Nejat; Uludağ, Hasan; Department of Biotechnology (2018)
Osteoporosis, the most common disease of bone, is a skeletal disorder associated with low bone mass, increase in bone fragility and in susceptibility to fractures. The high bone resorption rate is shown to be due to increased number and activity of the osteoclasts. Receptor Activator of Nuclear Factor kappa B (RANK)/ Receptor Activator of Nuclear Factor kappa B Ligand (RANKL) system plays a crucial role in osteoclast differentiation and bone remodeling. RANKL participates in differentiation and activation o...
Etiology of senile osteoporosis - A hypothesis
Atik, O. Sahap; Uslu, M. Murad; Eksioglu, Fatih; Satana, Tolgay (Ovid Technologies (Wolters Kluwer Health), 2006-02-01)
Osteoporosis is a major health problem characterized by compromised bone strength predisposing patients to an increased risk of fracture. It may cause morbidity and mortality in elderly men and women. The etiologic factors that lead to senile osteoporosis still are unclear.
Design and Development of a Low Cost Device for Bone Fracture Detection Using FFT Technique on MATLAB
Qadir, Zakria; Ali, Muhammad; Nesimoglu, Tayfun (2018-11-02)
Bone fracture is a common problem in daily life which occurs when high pressure is applied on bone or by simple accident and also due to osteoporosis and bone cancer. Different techniques are used today to detect bone fractures such as X-Ray, Computed Tomography (CT-scan), Magnetic Resonance Imaging (MRI) and Ultrasound. Among these four modalities, X-ray diagnosis is commonly used for fracture detection. However, if the fracture is complicated, a CT scan or MRI may be needed for further diagnosis and opera...
Design of a modular orthopedic implant
Erkan, Onur Mert; Tönük, Ergin; Department of Mechanical Engineering (2015)
Bone fracture due to trauma and bone defects by birth are very common in orthopedics, making their treatment crucial. In this study, a novel design to treat upper arm fractures is introduced and assessed mechanically. The design offers medical doctors longitudinal and angular flexibility when compared to widely used orthopedic plates. Hence the new design covers a variety of fracture types. Earlier conceptual designs are reviewed to demonstrate the progress of design. Mechanical performance of the final des...
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: