Targeting polymer therapeutics to bone

Abstract

An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems.

RGD peptide conjugated liposomal drug delivery system for enhance therapeutic efficacy in treating bone metastasis from prostate cancer

“…Recently, several targeted therapeutic agents that inhibit osteoclastmediated bone resorption (Vacuolar H + -ATPase inhibitors, RANKL inhibitor, c-Src Inhibitors, αvβ3 integrin inhibitors, Cathepsin K inhibitors, bisphosphonates, etc) [3,7] and restore osteoblast functions (DKK-1 inhibitors, Activin A inhibitors, etc) [8] have been studied or evaluated in clinical trials. Although these do reduce some degree of metastatic growth, providing symptomatic relief and regression of bone disease, none of them have been proven to significantly control tumor progression or improve overall survival [9].…”

Formulation and evaluation of osteotropic drug delivery system of methotrexate with a potential for passive bone targeting

“…This enhanced permeability and retention (EPR) of nanoparticles further aids in tumor targeting and retention. The application of passive targeting utilising the small particle size of the nanosystem to enter areas of less perfusion would prove effective in targeting bone infested with metastasized tumour cells as delivery of therapeutics to bone depends on the extravasation through vessels in or near the bone (Tautzenberger et al 2012;Low and Kopeček 2012). Further research has suggested that the vasculature in bone is fenestrated with pore sizes up to 80 nm, which exceeds the hydrodynamic size of most circulating nanomedicines.…”

Emulsion cross-linked chitosan/nanohydroxyapatite microspheres for controlled release of alendronate

“…Many biomaterial systems containing osteoinductive growth factors have gained great popularity in bone tissue engineering [8,9]. Varieties of microspheres-based drug delivery systems fabricated by biodegradable synthetic polymers, such as poly (lactic-co-glycolic) acid (PLGA), poly (e-caprolactone) (PCL) have been developed in previous studies [10,11].…”