Abstract

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.

Highlights

  • The human body contains soft tissues and organs which are supported and protected by the skeletal system

  • We found that all of them showed good transfection efficiency to osteoblastic cell line MC3T3-E1, MG63, HeLa, and HEK293 cells, but the one modified with naphthalimide showed even higher efficiency than lipofectamine 2000

  • It was successfully applied for in-situ monitoring of cellular uptake, DNA transportation, and release through non-invasive fluorescence imaging. We concluded that it can be used as a multifunctional non-viral delivery system for treating various bone disorders related to osteoblasts in future [18]

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Summary

Introduction

The human body contains soft tissues and organs which are supported and protected by the skeletal system. Because of complex anatomical structures and avascular regions, it is very difficult to treat human bones with non-targeted therapies They are risky because they deliver most of the drugs into visceral organs and have poor biocompatibility, bioavailability, and circulation time [4]. A number of non-viral vectors have been manufactured, improved, and used for the purpose of gene, siRNA, and drug delivery. Apart from these systems, physical methods including needle injection, balistic DNA injection, electroporation, sonoporation, photoporation, magnetofection, and hydroporation are used for transfection. We mainly discuss about the different kinds of non-viral delivery systems, their mechanistic features, and applications in the form of bone targeting moieties in the treatment of bone-related disorders at the molecular level

Non-Viral Delivery Systems
C O C CH2 N
Cationic Polymers
Calcium Phosphates
Metal Nanoparticles
Mechanism of Non-Viral Delivery to Bone Cells
Binding to Cell Surface
Endocytosis and Intracellular Processing
Nuclear Entry and Expression
Bone Targeting Systems
Tetracycline
Oligopeptides
Osteoblasts Targeting
Osteoclasts Targeting
Targeting with Bone Marrow Mesenchymal Stromal Cells
Therapeutic Agents for Bone-Related Diseases
Cathepsin K Inhibitors
V-ATPase Inhibitor
Src SH2 Inhibitors
Prostaglandins E2 Receptor Agonist and Antagonist
RANKL Inhibitors
Carbonic Anhydrases Inhibitors
Findings
Future Directions and Concluding Remarks
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