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Structural Diversity in Antiosteolytic Bisphosphonates: Deciphering Structure-Activity Trends in Ultra Long
Maria Vassaki1, Chrystalleni Hadjicharalambous2, Petri A Turhanen3
1Crystal Engineering, Growth and Design Laboratory, Department of Chemistry, University of Crete, Heraklion, Crete GR-71003, Greece.
ACS Applied Bio Materials
|November 20, 2023
Summary
Bisphosphonate (BP) drug release from tablets was studied, revealing that increased molecular interactions slow release. Structural features significantly influence BP release profiles, with amino-BPs generally showing slower release than alkyl-BPs.
Area of Science:
- Pharmacology
- Materials Science
- Drug Delivery
Background:
- Bisphosphonates (BPs) are crucial for bone conditions like osteoporosis.
- Low oral bioavailability necessitates higher doses, leading to side effects.
- Controlled release strategies offer a promising solution to improve BP therapy.
Purpose of the Study:
- To investigate the controlled release profiles of 15 bisphosphonates (BPs) and their analogs.
- To correlate BP release characteristics with their molecular and crystal lattice structures.
- To assess the impact of structural features on BP release from simulated gastric tablets.
Main Methods:
- Studied controlled release of 15 BPs (alkyl-BPs and amino-BPs) from cellulose/silica or cellulose/lactose/silica tablets.
- Simulated human stomach pH conditions for drug release experiments.
- Utilized 1H NMR peak integration to construct release curves (% BP release vs. time).
Main Results:
- Controlled release profiles were linked to BP structural features, including hydrogen and metal-oxygen bonds.
- Higher numbers of lattice interactions correlated with lower initial BP release rates.
- Alkyl-BP release slowed with increased alkyl side chain length; amino-BPs exhibited slower release than alkyl-BPs.
- No cytotoxicity was observed for alkyl- and amino-BPs on NIH3T3 cells.
Conclusions:
- Molecular and crystal lattice features significantly dictate BP release characteristics.
- BP release rate is inversely related to the total number of lattice interactions.
- Understanding these structure-release relationships can inform the design of improved bisphosphonate drug delivery systems.
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