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Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
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2009 (English)In: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 20, no 9, 1859-1867 p.Article in journal (Refereed) Published
Abstract [en]

The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO2 composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO2 to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.

Place, publisher, year, edition, pages
2009. Vol. 20, no 9, 1859-1867 p.
National Category
Engineering and Technology Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-122095DOI: 10.1007/s10856-009-3749-6ISI: 000268786400010PubMedID: 19399593OAI: oai:DiVA.org:uu-122095DiVA: diva2:308417
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Functional Ceramics in Biomedical Applications: On the Use of Ceramics for Controlled Drug Release and Targeted Cell Stimulation
Open this publication in new window or tab >>Functional Ceramics in Biomedical Applications: On the Use of Ceramics for Controlled Drug Release and Targeted Cell Stimulation
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Ceramics are distinguished from metals and polymers by their inorganic nature and lack of metallic properties. They can be highly crystalline to amorphous, and their physical and chemical properties can vary widely. Ceramics can, for instance, be made to resemble the mineral phase in bone and are therefore an excellent substitute for damaged hard tissue. They can also be made porous, surface active, chemically inert, mechanically strong, optically transparent or biologically resorbable, and all these properties are of interest in the development of new materials intended for a wide variety of applications. In this thesis, the focus was on the development of different ceramics for use in the controlled release of drugs and ions. These concepts were developed to obtain improved therapeutic effects from orally administered opioid drugs, and to reduce the number of implant-related infections as well as to improve the stabilization of prosthetic implants in bone.

Geopolymers were used to produce mechanically strong and chemically inert formulations intended for oral administration of opioids. The carriers were developed to allow controlled release of the drugs over several hours, in order to improve the therapeutic effect of the substances in patients with severe chronic pain. The requirement for a stable carrier is a key feature for these drugs, as the rapid release of the entire dose, due to mechanical or chemical damage to the carrier, could have lethal effects on the patient because of the narrow therapeutic window of opioids. It was found that it was possible to profoundly retard drug release and to achieve almost linear release profiles from mesoporous geopolymers when the aluminum/silicon ratio of the precursor particles and the curing temperature were tuned.

Ceramic implant coatings were produced via a biomimetic mineralization process and used as carriers for various drugs or as an ion reservoir for local release at the site of the implant. The formation and characteristics of these coatings were examined before they were evaluated as potential drug carriers. It was demonstrated that these coatings were able to carry antibiotics, bisphosphonates and bone morphogenetic proteins to obtain a sustained local effect, as they were slowly released from the coatings.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 99 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 780
Keyword
Controlled release, geopolymer, sol-gel, opioid, oral administration, oral dosage form, implant, titanium, hydroxyapatite, infection, strontium carbonate, strontium
National Category
Other Materials Engineering Materials Engineering Other Engineering and Technologies not elsewhere specified
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-132377 (URN)978-91-554-7930-5 (ISBN)
Public defence
2010-12-10, Polhelmsalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 13:00 (Swedish)
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Note

Felaktigt tryckt som Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 710

Available from: 2010-11-18 Created: 2010-10-19 Last updated: 2014-01-21Bibliographically approved

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Brohede, UlrikaForsgren, JohanMihranyan, AlbertEngqvist, HåkanStrömme, Maria

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