Development of bone seeker–functionalised microspheres as a targeted local antibiotic delivery system for bone infections
| العنوان: | Development of bone seeker–functionalised microspheres as a targeted local antibiotic delivery system for bone infections |
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| المؤلفون: | Keith Thompson, David Eglin, Dirk W. Grijpma, Olivier Guillaume, Stijn G. Rotman, Robert Geoff Richards, Thomas Fintan Moriarty |
| المساهمون: | TechMed Centre, Biomaterials Science and Technology |
| المصدر: | Journal of orthopaedic translation, 21, 136-145. Elsevier Journal of Orthopaedic Translation Journal of Orthopaedic Translation, Vol 21, Iss, Pp 136-145 (2020) |
| بيانات النشر: | Elsevier BV, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| وصف الملف: | application/pdf |
| تدمد: | 2214-031X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::11decf4c1daf4d9ffa959aafdb4f763e https://doi.org/10.1016/j.jot.2019.07.006 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....11decf4c1daf4d9ffa959aafdb4f763e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 2214031X |
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