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Review
. 2020 Oct;18(5):515-525.
doi: 10.1007/s11914-020-00620-4.

Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders

Kazuki Sawamoto  1 , J Víctor Álvarez  1 , Angélica María Herreño  1 , Francisco J Otero-Espinar  2 , Maria L Couce  3 , Carlos J Alméciga-Díaz  4 , Shunji Tomatsu  5   6   7   8
Affiliations
Review

Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders

Kazuki Sawamoto et al. Curr Osteoporos Rep. 2020 Oct.

Abstract

Purpose of review: The skeletal system provides an important role to support body structure and protect organs. The complexity of its architecture and components makes it challenging to deliver the right amount of the drug into bone regions, particularly avascular cartilage lesions. In this review, we describe the recent advance of bone-targeting methods using bisphosphonates, polymeric oligopeptides, and nanoparticles on osteoporosis and rare skeletal diseases.

Recent findings: Hydroxyapatite (HA), a calcium phosphate with the formula Ca10(PO4)6(OH)2, is a primary matrix of bone mineral that includes a high concentration of positively charged calcium ion and is found only in the bone. This unique feature makes HA a general targeting moiety to the entire skeletal system. We have applied bone-targeting strategy using acidic amino acid oligopeptides into lysosomal enzymes, demonstrating the effects of bone-targeting enzyme replacement therapy and gene therapy on bone and cartilage lesions in inherited skeletal disorders. Virus or no-virus gene therapy using techniques of engineered capsid or nanomedicine has been studied preclinically for skeletal diseases. Efficient drug delivery into bone lesions remains an unmet challenge in clinical practice. Bone-targeting therapies based on gene transfer can be potential as new candidates for skeletal diseases.

Keywords: Acidic amino acid oligopeptide; Bone-targeting; Metabolic rare skeletal disorders; Nanoparticles; Osteoporosis.

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Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.. Binding of bisphosphonate and oligopeptide conjugated drug to bone.
(A) Chemical structure of bisphosphonates. Two side chains (R and R’) determine the chemical prosperities of bisphosphonates. Bisphosphonates specifically bind to HA via coordination between two phosphate groups (and a hydroxyl group in R) and calcium ions of the crystal structure. (B) Negatively-charged acidic amino acid tagged drugs circulate in blood for longer time and delivered into bone more efficiently. These negatively-charged drugs bind with calcium site on HA. HA: hydroxyapatite.
Figure 2.
Figure 2.
Different components for targeting organic and inorganic nanoparticles to the bone. There are more unspecific nanoparticles whose targets are the vesicles inside cells or receptors on the cell surface. Organic materials as a family of CaP are more specific for targeting bone. These materials bind with the ligands like BPs, acidic oligopeptides, and aptamers to target bone. Other organic materials as silica, nanotubes of carbon, and magnetic nanoparticles are alternatives binding with the ligands and targeting bone lesions.
Figure 3.
Figure 3.. Future directions for osteoporosis treatment
AAV gene therapy with acidic oligopeptides (aspartic octapeptide-D8) in the capsid protein increases the specificity of the treatment in bone lesions. Additionally, miRNAs treatment with the AAV vector system increases the expression of the underlying gene directly in the bone.
See this image and copyright information in PMC

References

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