Abstract
The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.
Highlights
OverviewMore than 350 disorders encompass the collective group of skeletal dysplasias
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Bisphosphonates (BPs) are a family of synthetic drugs that have been widely used for several decades
Summary
More than 350 disorders encompass the collective group of skeletal dysplasias. Diseases involving the skeletal system are difficult to treat due to their complicated anatomical nature and the technical difficulties involving such a complex meshwork of different cell types, in the avascular cartilage region. Despite the difficulties, targeting the skeletal system is critical for treatment of bone lesions. The idea of creating moieties that would allow for targeted delivery of pharmaceuticals to bone tissue first came in the late 1950s. Common skeletal disorders include osteoporosis, metabolic skeletal dysplasia, and infectious bone disease. It is difficult to treat most diseases of the skeletal system with non-targeted drug delivery. MMaannyy nneeww ssyysstteemmssffoorr cceellll--ssppeecciiffiiccbboonneettaarrggeettiinngghhaavveebbeeeennddeevveellooppeeddiinntthheellaassttffeewwyyeeaarrss,, iinnccrreeaassiinnggddrruuggssttaabbiilliittyy,, iimmpprroovviinngg ddrruugg ssoolluubbiilliittyy,, aanndd pprreevveennttiinngg ddeeggrraaddaattiioonn ttoo eennaabblleeddrruuggssttoo rreeaacchh tthheeiirr ttaarrggeettss bbeeffoorree bbeeiinngg eelliimmiinnaatteedd iinn bblloooodd cciirrccuullaattiioonn. IInn tthhisisrerveivewie,ww, ewdiescudsisscduisffserdeniftfetyrepnets otfytpaersgetoifngtamrogieettiinegs amndoitehteiems oastnrdecethnet admvoasntcermeceenntts aindvtaarngceetminegnmtsoiinettyarcgoeutpinligngmtooieptryovcoiduepelifnfigcietontpdroelvivideerye.fWficeieanlstoddeilsivcuersys.hWowe athlseosedtisacrguestsinhgowsysthteemses tcaarngebteinugsesydsitnemspseccaifincboerucsoemdminosnpdecisifeiacsoers coofmthme osknedleistaelassyesstoefmth. e skeletal system
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