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Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders

  • Regenerative Biology and Medicine in Osteoporosis (S Bryant and M Krebs, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

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.

Summary

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.

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Abbreviations

AAV:

Adeno-associated virus

ADL:

Activity of daily living

ALN:

Alendronate

Asp:

Aspartic acid

BMD:

Bone mineral density

BPs:

Bisphosphonates

C6S:

Chondroitin-6-sulfate

D8:

Aspartic acid octapeptide

E2:

Estradiol

ERT:

Enzyme replacement therapy

GAG:

Glycosaminoglycans

GALNS:

N-Acetylgalactosamine 6-sulfate sulfatase

Glu:

Glutamic acid

HA:

Hydroxyapatite

HPP:

Hypophosphatasia

HS:

Heparan sulfate

HSCT:

Hematopoietic stem cell transplantation

IV:

Intravenous

KS:

Keratan sulfate

miRNA:

MicroRNA

MPS:

Mucopolysaccharidosis

N-BPs:

Nitrogen-containing BPs

NLC:

Nanostructured lipid carriers

NPs:

Nanoparticles

OVX:

Ovariectomized

PEG:

Polyethylene glycol

PLGA:

Poly (d,l-lactic-co-glycolic acid)

siRNA:

Small interfering RNA

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Funding

This work was supported by grants from National MPS Society Research Grant; Austrian MPS Society; The Carol Ann Foundation; Deborah McClellan and Brant Cali Foundation; The Radiant Hope donation; Angelo R. Cali & Mary V. Cali Family Foundation, Inc.; The Vain and Harry Fish Foundation, Inc.; The Bennett Foundation; Jacob Randall Foundation; Help Morquio Foundation; Vice Family; Lubert Family Foundation; Straughan Family; Paidipalli Family; and Nemours Funds. S.T. was supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of NIH under grant numbers P20GM103464 and P30GM114736. CJAD was supported by the Ministry of Science, Technology and Innovation (Contract 120380763212—PPTA # 8352).

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Authors and Affiliations

  1. Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA

    Kazuki Sawamoto, J. Víctor Álvarez, Angélica María Herreño & Shunji Tomatsu

  2. Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Santiago de Compostela, Santiago de Compostela, Spain

    Francisco J. Otero-Espinar

  3. Department of CC Foren. An. Pat, Gin. and Obst. and Paed. Neonatology Service, Metabolic Unit, University Clinic Hospital of Santiago de Compostela, Santiago de Compostela, Spain

    Maria L. Couce

  4. Institute for the Study of Inborn Errors of Metabolism, Faculty of Science, Pontificia Universidad Javeriana, Bogotá DC, Colombia

    Carlos J. Alméciga-Díaz

  5. Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan

    Shunji Tomatsu

  6. Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA

    Shunji Tomatsu

  7. Department of Biomedical Research, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE, 19899-0269, USA

    Shunji Tomatsu

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  1. Kazuki Sawamoto
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  2. J. Víctor Álvarez
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  3. Angélica María Herreño
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  4. Francisco J. Otero-Espinar
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  5. Maria L. Couce
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  7. Shunji Tomatsu
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Correspondence to Shunji Tomatsu.

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This article is part of the Topical Collection on Regenerative Biology and Medicine in Osteoporosis

Kazuki Sawamoto, J. Víctor Álvarez1, and Angélica María Herreño are joint first authors

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Sawamoto, K., Álvarez, J.V., Herreño, A.M. et al. Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders. Curr Osteoporos Rep 18, 515–525 (2020). https://doi.org/10.1007/s11914-020-00620-4

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