Hydroxybisphosphonate‐containing polymeric drug‐delivery systems designed for targeting into bone tissue

Abstract

ABSTRACT:The preparation and characterization of a novel polymeric drug-delivery system designed for bone targeting of antineoplastics is described. The system was based on biocompatible poly[N-(2-hydroxypropyl)methacrylamide] carrier containing hydroxybisphosphonate targeting moieties and the model radiotherapeutics 125 I or 111 In or the anticancer drug doxorubicin. The in vitro binding studies with hydroxyapatite as a bone model proved that the system was efficiently adsorbed on this mineral. The systems contained model drugs bound by stable (amide), hydrolytically cleavable (hydrazone) or enzymatically cleavable (Gly-PheLeu-Gly tetrapeptide) spacers. It was proven in vitro that, in the case of cleavable spacers, the drug could be released from the polymer carrier at a rate depending on the pH or enzymatic stimulus.

Enhanced anti-tumor activity and safety profile of targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate in the treatment of bone malignances

“…Different drug-delivery systems for several applications bearing a bone targeting moiety have been previously reported. This includes, HPMA copolymer-doxorubicin-hydroxybisphosphonate conjugate [64], HPMA copolymer–alendronate–paclitaxel conjugate [65] and fluorescein-labeled bone-targeted model conjugates for detection purposes bearing 1% loading of ALN or D-aspartic acid (D-Asp 8 ) oligopeptides [33,35,37,66–68]. The common denominator of these conjugates was that they all selectively accumulate in bone tissues regardless of relatively low loading percentage of their bone targeting moiety.…”

Targeting polymer therapeutics to bone

“…Rather, the amount of adsorbed polymer was affected by the number of targeting moieties as more ligands yielded higher binding avidity. The authors also concluded that there is a need for multiple targeting moieties to ensure that at least one is exposed [40]. Logically then, multiple targeting ligands become more critical as the nanomedicine size increases [41].…”

Nano‐sized Carrier Systems as New Materials for Nuclear Medicine

“…in bone metastases and broken/damaged areas [78][79][80]. This is why hydroxybisphosphonate moieties were also proposed for targeting of polymer carriers [81,82].…”

“…• Conjugates of molecularly water-soluble polymers [81,111] and antibodies [54]. Antibodies are biodegradable proteins with both passive and active targeting potential on their own.…”