Development of PEI-RANK siRNA Complex Loaded PLGA Nanocapsules for the Treatment of Osteoporosis

Bilecen, Deniz Sezlev
Uludag, Hasan
Hasırcı, Vasıf Nejat
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 efficacy specifically at the bone tissue. With better understanding of molecular pathology of bone, the use of small interfering RNA (siRNA) to inhibit translation of abnormal gene expression in cells is becoming a promising approach. In this study, we report a siRNA delivery system consisting of PEI:RANK siRNA complex entrapped in nanosized poly(lactic acid-co-glycolic acid) (PLGA) capsules intended to be used in the treatment of osteoporosis. The nanosize will enable the nanoparticles to be administered by intravenous injection. The RANK siRNA was complexed with polyethylenimine (PEI) and loaded into biodegradable PLGA nanocapsules (NCs). The PEI:RANK siRNA loaded nanocapsules significantly reduced (47%) RANK mRNA levels. The differentiation of osteoclast precursors to mature osteoclasts was significantly suppressed (approximate to 54%). The reduction in the osteoclastic activity of the differentiated osteoclasts (55%) was found to be statistically significant. The siRNA delivery system developed in the study is planned to be tested i.v. in mouse and has the potential to be used as a novel alternative approach for the systemic treatment of osteoporosis.


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 (2017-01-01)
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...
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...
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...
A new therapeutic combination for osteosarcoma: Gemcitabine and Clofazimine co-loaded liposomal formulation
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Osteosarcoma is the most common cancer in bone. Drug resistance is a challenge of current treatments that needs to be improved with novel treatment strategies. In this research, a new dual drug delivery system was developed with Gemcitabine (GEM) and Clofazimine (CLF) co-loaded liposome formulations. GEM is a well-known anticancer agent and CLF is a leprostatic and anti-inflammatory drug recently recognized as effective on cancer. GEM and CLF co-loaded liposomal formulation was achieved with compartmentaliz...
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.
Citation Formats
D. S. Bilecen, H. Uludag, and V. N. Hasırcı, “Development of PEI-RANK siRNA Complex Loaded PLGA Nanocapsules for the Treatment of Osteoporosis,” TISSUE ENGINEERING PART A, pp. 34–43, 2018, Accessed: 00, 2020. [Online]. Available: