Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone
Stijn G Rotman1,2, Thomas F Moriarty1, Benjamin Nottelet3
1AO Research Institute Davos, 7270 Davos Platz, Switzerland.
Pharmaceutics
|September 22, 2020
Summary
New biodegradable microspheres target bone infections by delivering antibiotics directly to affected bone tissue. These microspheres, functionalized for bone affinity, show sustained antibiotic release and inhibit bacterial growth, offering a promising approach for treating persistent bone infections.
Area of Science:
- Biomaterials Science
- Infectious Diseases
- Drug Delivery Systems
Background:
- Bone infections are a significant complication of bone fractures, often caused by bacteria like *Staphylococcus aureus* that evade conventional treatments.
- Effective local antibiotic delivery is crucial for preventing and treating bone infections, especially when bacteria reside within bone canaliculi.
- Current antibiotic treatments struggle to reach bacteria embedded within bone tissue, necessitating novel delivery strategies.
Purpose of the Study:
- To develop a biodegradable microsphere carrier system for targeted local antibiotic delivery to bone tissue.
- To functionalize microspheres with bone-targeting ligands to enhance their affinity for infected bone mineral.
- To evaluate the antibiotic loading, sustained release, and in vitro efficacy of the developed bone-targeting microspheres.
Main Methods:
- Biodegradable poly(ϵ-caprolactone) (PCL) microspheres were fabricated using oil-in-water emulsion with carboxylated poly(vinyl alcohol) (cPVA) surfactant.
- PCL/cPVA microspheres were functionalized with aspartic acid oligomers (ASP) to impart bone-targeting properties.
- Microspheres were loaded with Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) antibiotics, and their release kinetics and antibacterial activity were assessed in vitro.
Main Results:
- The developed PCL/cPVA-ASP microspheres demonstrated sustained release of embedded antibiotics over a 6-day period.
- In vitro studies showed significant inhibition of bacterial growth by the antibiotic-loaded microspheres.
- Functionalized PCL/cPVA-ASP microspheres exhibited enhanced binding affinity to mineralized substrates compared to non-functionalized microspheres.
Conclusions:
- Biodegradable, bone-targeting microspheres loaded with antibiotics represent a promising strategy for localized treatment of bone infections.
- The sustained release and enhanced bone affinity of these microspheres could improve therapeutic outcomes for persistent bone infections.
- Further development of this antibiotic delivery system holds potential for combating challenging bone-related bacterial infections.
