Targeting systemically administered proteins to bone by bisphosphonate conjugation

Area of Science:

• Biomaterials Science
• Drug Delivery
• Orthopedics

Background:

• Developing targeted protein delivery systems is crucial for enhancing therapeutic efficacy.
• Bone-specific targeting strategies are needed to improve treatments for bone disorders.

Purpose of the Study:

• To evaluate the efficacy of aminobisphosphonate (aminoBP) conjugation for enhancing bone-specific protein delivery.
• To determine if aminoBP conjugation increases the systemic delivery of model proteins (bovine serum albumin and lysozyme) to bone.

Main Methods:

• Conjugation of a bone-seeking aminobisphosphonate (aminoBP) to bovine serum albumin (BSA) and lysozyme (LYZ).
• Radiolabeling of unmodified and aminoBP-conjugated proteins with iodine-125 ((125)I).
• Intravenous (IV) and subcutaneous administration of labeled proteins in normal and osteopenic rats, followed by organ distribution analysis.

Main Results:

• AminoBP-BSA conjugates showed a 2.0- to 3.7-fold increase in bone delivery compared to unmodified BSA in young rats.
• In osteopenic rats, aminoBP-BSA enhanced bone delivery by 2.2- to 7.5-fold.
• AminoBP-LYZ conjugates demonstrated a 3.7- to 5.6-fold increase in bone delivery in normal rats.
• Both IV and subcutaneous administration routes effectively increased bone targeting of aminoBP-conjugated proteins.

Conclusions:

• Conjugation of bone-seeking aminobisphosphonates to proteins significantly improves their delivery to mineralized tissues.
• This targeted delivery approach holds promise for enhancing the efficacy of bone-forming recombinant proteins by improving their localization to bone.