Influence of the Molecular Weight and Charge of Antibiotics on Their Release Kinetics From Gelatin Nanospheres

Abstract

In this study, we investigated the fundamental relationship between the physicochemical characteristics of antibiotics and the kinetics of their release from gelatin nanospheres. We observed that antibiotics of high molecular weight (colistin and vancomycin) were released in a sustained manner from oppositely charged gelatin carriers for more than 14 d, as opposed to antibiotics of low molecular weight (gentamicin and moxifloxacin) which were released in a burst-like manner. The release kinetics of positively charged colistin strongly correlated with the rate of the enzymatic degradation of gelatin. To elucidate the differences among release kinetics of antibiotics, we explored the mechanism of interactions between antibiotics and gelatin nanospheres by monitoring the kinetics of release of antibiotics as a function of pH, ionic strength, and detergent concentrations. These studies revealed that the interactions between antibiotics and gelatin nanospheres were mainly dominated by (i) strong electrostatic forces for colistin; (ii) strong hydrophobic and electrostatic forces for vancomycin; (iii) weak electrostatic and hydrophobic forces for gentamicin; and (iv) weak hydrophobic forces for moxifloxacin. These results confirm that release of antibiotics from gelatin nanospheres strongly depends on the physicochemical characteristics of the antibiotics.

Composite Colloidal Gels Made of Bisphosphonate‐Functionalized Gelatin and Bioactive Glass Particles for Regeneration of Osteoporotic Bone Defects

“…Moreover, in vivo investigations have shown that these materials can be used as osteoconductive bone fillers with in vivo drug release ability . Although the assembly of biomaterials from colloidal particles was shown to be a promising strategy for the development of injectable and self‐healing gels with tissue regenerative[8a,b,9b,c,20] and drug release[9a,21,22] capabilities, the potential of colloidal gel systems for regeneration of osteoporotic bone defects has never been explored before. Hence, the goal of this study was to develop injectable and self‐healing composite colloidal gels that combine mechanical robustness with the capacity to regenerate osteoporotic bone through the concerted action of anabolic and anticatabolic stimuli.…”

“…These gels are solely composed of colloidal particles. Various types of particles can be used as colloidal building blocks, which can be loaded or functionalized with different types of drugs or biomolecules . By utilizing reversible, noncovalent interparticle bonds, self‐healing colloidal gels can be prepared that recover their mechanical properties after destructive shearing upon extrusion through needles.…”

“…We have recently shown[8a‐c,9b,c,10] that gelatin‐based colloidal gels are promising materials for applications in bone regeneration. Nevertheless, colloidal gels composed of only soft organic particles are mechanically weak and lack sufficient bioactivity.…”

“…Nevertheless, colloidal gels composed of only soft organic particles are mechanically weak and lack sufficient bioactivity. [8c,d] The performance of these purely organic colloidal systems was enhanced previously by (i) modification of organic particles with functionally and biologically active molecules[9c,d,11] or (ii) inclusion of bioactive inorganic particles. [8a,b] Regarding strategy (i), we have recently demonstrated that functionalization of gelatin nanoparticles with bisphosphonate molecules enhances their binding affinity toward calcium‐containing minerals, i.e., hydroxyapatite, and induces sustained release of bisphosphonates.…”

Self‐Healing Biomaterials: From Molecular Concepts to Clinical Applications

“…[81b] The particle size of these colloidal gels strongly influenced the functional properties of resulting colloidal gels as gels made of gelatin microspheres were less elastic, less cohesive, less injectable and non‐self‐healing, as opposed to colloidal gels prepared from gelatin nanoparticles . In vitro investigations showed that the nanostructured gelatin‐based colloidal gels facilitated controlled release of multiple growth factors as well as antibiotics . In vivo investigations revealed that these colloidal gelatin gels allowed controlled delivery of angiogenic basic fibroblast growth factor and osteogenic bone morphogenetic protein‐2 for the regeneration of bone defects.…”