Development of bone seeker–functionalised microspheres as a targeted local antibiotic delivery system for bone infections
| Autor: | Keith Thompson, David Eglin, Dirk W. Grijpma, Olivier Guillaume, Stijn G. Rotman, Robert Geoff Richards, Thomas Fintan Moriarty |
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| Přispěvatelé: | TechMed Centre, Biomaterials Science and Technology |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Bone seeker lcsh:Diseases of the musculoskeletal system medicine.medical_treatment Pharmacology Bone targeting Bone Infection 03 medical and health sciences 0302 clinical medicine Osteoclast medicine Orthopedics and Sports Medicine Microparticle 030203 arthritis & rheumatology Bone mineral Alendronate Chemistry Osteomyelitis Bisphosphonate 030104 developmental biology medicine.anatomical_structure Drug delivery Original Article lcsh:RC925-935 Drug carrier Bone infection |
| Zdroj: | Journal of orthopaedic translation, 21, 136-145. Elsevier Journal of Orthopaedic Translation Journal of Orthopaedic Translation, Vol 21, Iss, Pp 136-145 (2020) |
| ISSN: | 2214-031X |
| Popis: | Objective: Bone infections are challenging to treat because of limited capability of systemic antibiotics to accumulate at the bone site. To enhance therapeutic action, systemic treatments are commonly combined with local antibiotic-loaded materials. Nevertheless, available drug carriers have undesirable properties, including inappropriate antibiotic release profiles and nonbiodegradability. To alleviate such limitations, we aim to develop a drug delivery system (DDS) for local administration that can interact strongly with bone mineral, releasing antibiotics at the infected bone site. Methods: Biodegradable polyesters (poly (ε-caprolactone) or poly (D,l-lactic acid)) were selected to fabricate antibiotic-loaded microspheres by oil in water emulsion. Antibiotic release and antimicrobial effects on Staphylococcus aureus were assessed by zone of inhibition measurements. Microsphere bone affinity was increased by functionalising the bisphosphonate drug alendronate to the microsphere surface using carbodiimide chemistry. Effect of bone targeting microspheres on bone homeostasis was tested by looking at the resorption potential of osteoclasts exposed to the developed microspheres. Results: In vitro, the antibiotic release profile from the microspheres was shown to be dependent on the polymer used and the microsphere preparation method. Mineral binding assays revealed that microsphere surface modification with alendronate significantly enhanced interaction with bone-like materials. Additionally, alendronate functionalised microspheres did not differentially affect osteoclast mineral resorption in vitro, compared with nonfunctionalised microspheres. Conclusion: We report the development and characterisation of a DDS which can release antibiotics in a sustained manner. Surface-grafted alendronate groups enhanced bone affinity of the microsphere construct, resulting in a bone targeting DDS. The Translational Potential of this Article: The DDS presented can be loaded with hydrophobic antibiotics, representing a potential, versatile and biodegradable candidate to locally treat bone infection. Keywords: Alendronate, Bone infection, Bone targeting, Drug delivery, Microparticle, Osteomyelitis |
| Databáze: | OpenAIRE |
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