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Abstract
A major problem with conventional methods of drug administration is the lack of control over the rate of drug release, the drug concentration at the target site and systematic side effectsdue to nonspecific biodistribution of the drug [1]. On-demand drug delivery systems (DDS) have the potential to address these issues by delivering the drug at a predetermined rate, a desired site of action, and for a definite time duration, all of which enhances the therapeutic efficacy of the drug while reducing its toxicity [1–6]. Particularly, light-responsive DDS are considered advantageous in terms of convenience and ease of use [7–10], having the potential for remote precise spatial and temporal control [11]. Light can be easily switched ‘off’ and ‘on’, and the rate of drug release can be tuned remotely according to the duration of exposure [12–14].
Most photo-responsive compounds respond exclusively to ultraviolet (UV) light, which is harmful to the tissues and has a low penetration depth [7,15]. Also, the light-triggered DDS that have been designed so far, have certain limitations: the majority are based on micelles as drug carriers, and the triggered-release mechanism is relying on disassembly and disruption of the micelles; the polymer components together with the drug will therefore be released in the environment and may be toxic. These DDS mostly suffer from high premature drug leakage before reaching the target site, and most of them lack the reversibility, i.e. do not possess the capability to stop the release again after the initial trigger.
The recently developed supercritical carbon dioxide (scCO2) technology for producing interpenetrating polymer networks (IPNs) by impregnating silicone elastomer with different guest polymers has provided the opportunity of developing unique DDS with flexibility in terms of choice of drug and guest polymer [16–21]. However, until now there has been no research on stimuli-responsive drug release from silicone-based IPNs.
This thesis has focused on developing a light-triggered IPN-based DDS that can trigger the release of a drug from the bulk material without degradation and disruption of the system, and with the release repeatedly switched on and off, simply by switching the light on and off.
Most photo-responsive compounds respond exclusively to ultraviolet (UV) light, which is harmful to the tissues and has a low penetration depth [7,15]. Also, the light-triggered DDS that have been designed so far, have certain limitations: the majority are based on micelles as drug carriers, and the triggered-release mechanism is relying on disassembly and disruption of the micelles; the polymer components together with the drug will therefore be released in the environment and may be toxic. These DDS mostly suffer from high premature drug leakage before reaching the target site, and most of them lack the reversibility, i.e. do not possess the capability to stop the release again after the initial trigger.
The recently developed supercritical carbon dioxide (scCO2) technology for producing interpenetrating polymer networks (IPNs) by impregnating silicone elastomer with different guest polymers has provided the opportunity of developing unique DDS with flexibility in terms of choice of drug and guest polymer [16–21]. However, until now there has been no research on stimuli-responsive drug release from silicone-based IPNs.
This thesis has focused on developing a light-triggered IPN-based DDS that can trigger the release of a drug from the bulk material without degradation and disruption of the system, and with the release repeatedly switched on and off, simply by switching the light on and off.
Original language | English |
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Place of Publication | Kgs. Lyngby, Denmark |
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Publisher | DTU Bioengineering |
Number of pages | 112 |
Publication status | Published - 2020 |
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On-demand reversible light-triggered drug delivery systems based on interpenetrating polymer networks
Ghani, M. (PhD Student), Grassi, M. (Examiner), Boisen, A. (Examiner), Kamaly, N. (Examiner), Emnéus, J. (Main Supervisor), Heiskanen, A. R. (Supervisor) & Alm, M. (Supervisor)
01/06/2017 → 25/01/2021
Project: PhD