Bone Diseases: Current Approach and Future Perspectives in Drug Delivery Systems for Bone Targeted Therapeutics

Abstract

Bone diseases include a wide group of skeletal-related disorders that cause mobility limitations and mortality. In some cases, e.g., in osteosarcoma (OS) and metastatic bone cancer, current treatments are not fully effective, mainly due to low patient compliance and to adverse side effects. To overcome these drawbacks, nanotechnology is currently under study as a potential strategy allowing specific drug release kinetics and enhancing bone regeneration. Polymers, ceramics, semiconductors, metals, and self-assembled molecular complexes are some of the most used nanoscale materials, although in most cases their surface properties need to be tuned by chemical or physical reactions. Among all, scaffolds, nanoparticles (NPs), cements, and hydrogels exhibit more advantages than drawbacks when compared to other nanosystems and are therefore the object of several studies. The aim of this review is to provide information about the current therapies of different bone diseases focusing the attention on new discoveries in the field of targeted delivery systems. The authors hope that this paper could help to pursue further directions about bone targeted nanosystems and their application for bone diseases and bone regeneration.

Keywords: bone diseases; bone regeneration; calcium phosphate; nanotechnology; targeted delivery systems.

Figure 1

Schematic representation of methotrexate (MTX)-encapsulated dendrimers for the treatment of bone metastasis which allow the suppression of tumor cells in mice.

Figure 2

Mechanism of action of liposomal muramyl tripeptide phosphatidyl ethanolamine (MTP-PE). It is a specific ligand of NOD2 which is an intracellular receptor in monocytes, dendritic cells and macrophages: the activation of these cells produces cytokines e.g., tumor necrosis factor (TNF), several interleukins (IL), e.g., IL-6, IL-8, IL-12 and adhesion molecules without effects on tumorigenic cells.

Figure 3

Scheme representing the preparation of simvastatin-loaded alginate gel which becomes a soft carrier after injection in mice. Amorphous calcium phosphate (ACP) acts like a buffer to avoid the acidification of the gel-environment prolonging drug release.

Figure 4

Schematic representation of the mechanism of action of calcium phosphate (CaP) coated nanoparticles (NPs) loaded with antibiotic. Negatively charged NPs could selectively bind Ca²⁺ ions situated on bone surface.

Figure 5

Schematic representation of the advantageous characteristics of bone injected calcium phosphate cements (CaPCs).

Figure 6

Schematic diagram showing citing frequency of each bone drug delivery approach as percentage of total number of the studies cited in this review.