Bone-Specific Drug Delivery for Osteoporosis and Rare Skeletal Disorders

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 Ca 10 (PO 4 ) 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 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.

Reduced Circulating Levels of miR-491-5p and miR-485-3p Are Associated with the Occurrence of Vertebral Fractures in Postmenopausal Women with Osteoporosis

“…The skeletal system plays a major role in supporting body structure and movement and maintaining mineral balance in the human body. Abnormality of the skeletal system will cause a variety of skeletal diseases such as osteoporosis, osteoarthritis, metabolic bone dysplasia, and bone cancer [ 17 ]. Osteoporosis is characterized by fragile bones, reduced BMD, and degradation of bone microstructure, leading to an increased risk of vertebral fracture, hip fracture, and fracture in other skeletal sites [ 18 ].…”

Applications of Calcium-Based Nanomaterials in Osteoporosis Treatment

“…In particular, nHA has been shown to have pro-osteogenic properties and can be combined with antiosteoclastogenic ingredients to carry out the one-plus-one antiosteoporosis strategy. As a typical example, coupling nHA with the classic antiosteoclastogenic bisphosphate drugs is a common strategy to build synergistic antiosteoporosis formulations. ,,,, As previously mentioned, the coordination bond between the phosphoryl of bisphosphonates and Ca 2+ on nHA not only makes the loading process fast and simple but also imparts a bone targeting ability to the combined formulations, which improves bioavailability of the bisphosphates . For instance, zoledronate-loaded nHA built through simple absorption resulted in a prominent bone mass increase in OVX rats due to the synergistic antiosteoporotic effect of both components (Figure a) .…”

Role of Phosphorus-Containing Molecules on the Formation of Nano-Sized Calcium Phosphate for Bone Therapy

“…Compared to normal non-degradable drug carriers, CaP materials exhibit superior advantages such as excellent biodegradability and biological responses, since the metabolites are ubiquitous ions of calcium and phosphate (Pina et al, 2015;Jiang et al, 2018). Among the multifarious types of calcium phosphate, amorphous calcium phosphate (ACP) is the primary phase that can first precipitate from super-saturated aqueous solution owing to its low surface energy relative to that of hydroxyapatite (HAP) and octacalcium phosphate (OCP) (Sawamoto et al, 2020). Moreover, ACP is a relatively outstanding biomaterial with superior biodegradability and osteoinductivity (Qi et al, 2019).…”

“…Calcium phosphate (CaP) is the principal inorganic constituent of bones and teeth in vertebrates ( Dorozhkin and Epple, 2002 ; Sawamoto et al, 2020 ). The CaP materials are essential biomaterials with excellent biocompatibility, and therefore, they have wide applications in biomedical areas, including bone regeneration and coating of implants or fillers in bones or teeth ( Wang and Yeung, 2017 ; Li et al, 2021 ).…”

“…Among the multifarious types of calcium phosphate, amorphous calcium phosphate (ACP) is the primary phase that can first precipitate from super-saturated aqueous solution owing to its low surface energy relative to that of hydroxyapatite (HAP) and octacalcium phosphate (OCP) ( Sawamoto et al, 2020 ). Moreover, ACP is a relatively outstanding biomaterial with superior biodegradability and osteoinductivity ( Qi et al, 2019 ).…”