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Self-setting bioceramic microscopic protrusions for transdermal drug delivery
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
2014 (English)In: Journal of materials chemistry. B, ISSN 2050-750X, E-ISSN 2050-7518, Vol. 2, no 36, 5992-5998 p.Article in journal (Refereed) Published
Abstract [en]

Microneedle (MN) technology offers both an efficient and a minimally invasive transdermal drug delivery strategy. The current MNs, made of silicon and metal, have poor biocompatibility and low drug loading, while the polymer MNs have some constraints related to mechanical strength and storage conditions. In this study, self-setting bioceramics were explored as substitutes for the current MN materials for the first time. Self-setting bioceramic microneedles were fabricated using a master mold by a procedure under mild conditions, which could minimize the drug degradation during fabrication and also facilitates a higher drug loading capability than the other current ceramic microneedles. The drug release and mechanical strength were correlated with the microstructure and porosity of the needles. As observed by SEM and microCT, the ceramic paste could fully fill the geometry of the mould and was cured into an array of micro-sized needles. The drug release study showed that the release rate from this type of MN array could be controlled by the bulk surface area, porosity and resorption rate of the ceramic needles. Applying the MNs to porcine skin indicated that the needles were able to pierce the stratum corneum of the skin. We successfully prepared the bioceramic needles that have high mechanical strength and are resorbable, which can promote safe, efficient and successful transdermal drug delivery.

Place, publisher, year, edition, pages
2014. Vol. 2, no 36, 5992-5998 p.
National Category
Bio Materials Engineering and Technology
Research subject
Engineering Science with specialization in Materials Science
Identifiers
URN: urn:nbn:se:uu:diva-233125DOI: 10.1039/c4tb00764fISI: 000341300300007OAI: oai:DiVA.org:uu-233125DiVA: diva2:750681
Conference
microneedles 2014, Baltimore, May 19-21, 2014
Available from: 2014-09-29 Created: 2014-09-29 Last updated: 2017-12-05
In thesis
1. Ceramic Materials for Administration of Potent Drugs
Open this publication in new window or tab >>Ceramic Materials for Administration of Potent Drugs
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aimed to investigate and document the potential of applying ceramics in two specific drug delivery applications: tamper-resistant opioid formulations and transdermal enhancement protrusions.

Geopolymers were developed into the matrix for a tamper-resistant formulation, aiming to protect drug substances from non-medical abuse. The synthesis conditions and excipients composition of the geopolymer-based formulation were modified in this work to facilitate a stable and extended drug delivery. Results showed that 37ºC 100% humidity for 48 hours were applicable conditions to obtain geopolymer with suitable mechanical strength and porosity. Moreover, it was found that the integration of poly(methyl acrylate) into the geopolymer-based formulation could reduce the drug release at low pH and, meanwhile, maintain the mechanical strength. Therefore, the geopolymer-based drug formulations concluded from these studies were applied in oral and transdermal delivery systems. Evidence of the tamper-resistance of geopolymer-based oral and transdermal formulations was documented and compared to the corresponding commercial opioid formulations. The results provided experimental support for the positive effects of geopolymers as drug carriers for the tamper-resistance of oral and transdermal delivery systems.

Self-setting bioceramics, calcium phosphate and calcium sulfate were fabricated into transdermal enhancement protrusions in this work for the first time. Results showed that, under mild conditions, both bioceramics could form pyramid-shaped needles in the micron size. The drug release from these needles could be controlled by the bulk surface area, porosity and degradation of the bioceramics. An in vitro insertion test showed that the bioceramic microneedles had enough mechanical strength to insert into skin. Further optimization on the geometry of needles and the substrate material was also performed. The higher aspect-ratio needles with a flexible and self-swellable substrate could release most of the drug content within 4 hours and could penetrate through the stratum corneum by manual insertion. This study explored the potential application of bioceramics in transdermal enhancement protrusions and showed promising indication of their future developments.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 65 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1235
Keyword
Tamper-resistance, Oral formulation, Transdermal formulation, Biomaterials, Microneedles
National Category
Biomaterials Science Ceramics
Identifiers
urn:nbn:se:uu:diva-245031 (URN)978-91-554-9188-8 (ISBN)
Public defence
2015-04-28, Polhemssalen, Lägerhyddsvägen 2, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2015-04-07 Created: 2015-02-24 Last updated: 2015-04-17

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Cai, BingXia, WeiBredenberg, SusanneEngqvist, Håkan

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