Development of Double-Controlled Drug Eluting Stents with Nanotechnology
Session Number
Project ID: MEDH 29
Advisor(s)
Dr. Dong-Hyun Kim; Northwestern University Feinberg School of Medicine
Kijung Kwak, Pre-Med Student
Bo Yu, Researcher
Discipline
Medical and Health Sciences
Start Date
22-4-2020 8:50 AM
End Date
22-4-2020 9:05 AM
Abstract
For the past few decades, various of drug-eluting stents (DES), coated with an additional layer over stents mesh as a drug loading platform, were developed to steadily emit a drug for preventing the hyperplasia, and these stents could provide direct delivery of an antitumor drug to the local site and reduce the rate of blockage in the case of tumor recurrence. However, the clinic's outcomes of these DES were limited by its poor drug release kinetics and subsequent damage to adjacent normal digestive epithelial cells. Drug release from pH- and enzyme sensitive polymeric delivery systems is mainly attributed to stimuli-triggered degradation. Usually, if the pH is lower, then the rates of polymer erosion and drug release are faster, which can cause adverse effects. Also, temperature affects the solubility of the polymer and can speed up degradation, and the encapsulated drugs in the polymer will be released. Furthermore, encapsulating drug-loaded nanoparticle not only increases drug efficiency, but also allows more uniform distribution and possibly sustained drug release than encapsulating a pure drug. Encapsulating a hydrophilic drug within the hydrophobic matrix, however, is a challenge due to the non-uniform drug precipitates, which contribute to their quick release. Studies have shown that release kinetics of selected solutes from such biodegradable polymeric matrices are not simply driven by matrices, but also that the concentration gradient and the shape of the coating seem to have a more profound impact on the release rate. To solve this problem, Northwestern University BIGMed Lab developed gemcitabine-loaded mesoporous silica nanoparticles (gMSNP), and the nanoparticles were coated onto the stent with biodegradable poly(lactic-coglycolic) acid (PLGA) polymer. Here, the drug release kinetics were tested and evaluated the potential controlled gemcitabine (GEM) release from the stent. GEM loading efficiency onto the silica nanoparticles, drug release kinetics were determined by taking samples of the buffer solution at different time points to measure the drug concentration. Concentration of the drug in each sample was quantified by measuring its UV-Vis Absorbance at 265-300 nm range and comparing to a standard curve. The data for the drug release collected showed a smaller burst release followed by a near zero-order release for the DES, which shows a constant rate of drug release over time. At 2 weeks after the initial release, the DES had 40 percent less drug released than PLGA loaded with pure GEM precipitates (p < 0.05). The project measured improved drug release kinetics of the developed nanocomposite layers on the stent. The measured sustained drug release will eventually reduce the rate of restenosis that can be induced by stents.
Development of Double-Controlled Drug Eluting Stents with Nanotechnology
For the past few decades, various of drug-eluting stents (DES), coated with an additional layer over stents mesh as a drug loading platform, were developed to steadily emit a drug for preventing the hyperplasia, and these stents could provide direct delivery of an antitumor drug to the local site and reduce the rate of blockage in the case of tumor recurrence. However, the clinic's outcomes of these DES were limited by its poor drug release kinetics and subsequent damage to adjacent normal digestive epithelial cells. Drug release from pH- and enzyme sensitive polymeric delivery systems is mainly attributed to stimuli-triggered degradation. Usually, if the pH is lower, then the rates of polymer erosion and drug release are faster, which can cause adverse effects. Also, temperature affects the solubility of the polymer and can speed up degradation, and the encapsulated drugs in the polymer will be released. Furthermore, encapsulating drug-loaded nanoparticle not only increases drug efficiency, but also allows more uniform distribution and possibly sustained drug release than encapsulating a pure drug. Encapsulating a hydrophilic drug within the hydrophobic matrix, however, is a challenge due to the non-uniform drug precipitates, which contribute to their quick release. Studies have shown that release kinetics of selected solutes from such biodegradable polymeric matrices are not simply driven by matrices, but also that the concentration gradient and the shape of the coating seem to have a more profound impact on the release rate. To solve this problem, Northwestern University BIGMed Lab developed gemcitabine-loaded mesoporous silica nanoparticles (gMSNP), and the nanoparticles were coated onto the stent with biodegradable poly(lactic-coglycolic) acid (PLGA) polymer. Here, the drug release kinetics were tested and evaluated the potential controlled gemcitabine (GEM) release from the stent. GEM loading efficiency onto the silica nanoparticles, drug release kinetics were determined by taking samples of the buffer solution at different time points to measure the drug concentration. Concentration of the drug in each sample was quantified by measuring its UV-Vis Absorbance at 265-300 nm range and comparing to a standard curve. The data for the drug release collected showed a smaller burst release followed by a near zero-order release for the DES, which shows a constant rate of drug release over time. At 2 weeks after the initial release, the DES had 40 percent less drug released than PLGA loaded with pure GEM precipitates (p < 0.05). The project measured improved drug release kinetics of the developed nanocomposite layers on the stent. The measured sustained drug release will eventually reduce the rate of restenosis that can be induced by stents.