Drug-Inclusive Inorganic–Organic Hybrid Systems for the Controlled Release of the Osteoporosis Drug Zoledronate

Abstract

Bisphosphonates (BPs) are common pharmaceutical treatments used for calcium- and bone-related disorders, the principal one being osteoporosis. Their antiresorptive action is related to their high affinity for hydroxyapatite, the main inorganic substituent of bone. On the other hand, the phosphonate groups on their backbone make them excellent ligands for metal ions. The combination of these properties finds potential application in the utilization of such systems as controlled drug release systems (CRSs). In this work, the third generation BP drug zoledronate (ZOL) was combined with alkaline earth metal ions (e.g., Sr2+ and Ba2+) in an effort to synthesize new materials. These metal–ZOL compounds can operate as CRSs when exposed to appropriate experimental conditions, such as the low pH of the human stomach, thus releasing the active drug ZOL. CRS networks containing Sr2+ or Ba2 and ZOL were physicochemically and structurally characterized and were evaluated for their ability to release the free ZOL drug during an acid-driven hydrolysis process. Various release and kinetic parameters were determined, such as initial rates and release plateau values. Based on the drug release results of this study, there was an attempt to correlate the ZOL release efficiency with the structural features of these CRSs.

Structural Diversity in Antiosteolytic Bisphosphonates: Deciphering Structure–Activity Trends in Ultra Long Controlled Release Phenomena

“…Herein, the new crystal structures of the compounds ETID­(Na 4 ), ETID­(K), HMBP­(Na 2 ) ((hydroxymethylene)­bisphosphonic cif files of these compounds have been deposited with the Supporting Information, and their CCDC codes are ETID­(Na 4 ) 2279435, ETID­(K) 2277643, HMBP­(Na 2 ) 2279436, and C1NBP 2279438. The commonly used crystallographic techniques were employed for the compounds ETID­(Na 4 ), ETID­(K), and HMBP­(Na 2 ) and have been described previously in detail. , The structure of the compound C1NBP was solved by ab initio methods using previously described methodologies …”

“…The commonly used crystallographic techniques were employed for the compounds ETID(Na 4 ), ETID(K), and HMBP(Na 2 ) and have been described previously in detail. 39,40 The structure of the compound C1NBP was solved by ab initio methods using previously described methodologies. 60 Fabrication of the BP Drug Release Systems.…”

“…37 Our group have included several structurally characterized first and second generation metal-BP systems in a comparative study, 38 and later focused on detailed investigations on metalrisedronate 39 and metal-zoledronate systems. 40 In this paper, we present a systematic study of the controlled release profiles of 15 structurally characterized BPs (drugs and structural analogs, in the acid or alkali metal salt form) from inhouse fabricated tablets containing three (cellulose, lactose, and silica) or two (cellulose, and silica) excipients. The release experiments were carried out in aqueous systems that simulate the pH of the human stomach (∼1.3).…”

“…Nanoscale coordination polymers containing exceptionally high loadings of BPs were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to enhanced cytotoxicity against human lung and pancreatic cancer cells . Our group have included several structurally characterized first and second generation metal-BP systems in a comparative study, and later focused on detailed investigations on metal-risedronate and metal-zoledronate systems …”

Metal–Organic Frameworks (MOFs) and Their Composites as Emerging Biomaterials for Osteoarthritis Treatment

“…While MOFs have been increasingly applied as drug delivery systems for bone-related diseases [ 12 , 13 ], the use of MOFs specifically for cartilage repair in the field of OA treatment has not been extensively studied. Moreover, the potential synergistic effects when augmenting MOFs with hydrogels to achieve longer retention and sustained therapeutic function remained largely unexplored until recent years.…”