THESIS
2022
1 online resource (13 unnumbered pages, 49 pages) : illustrations (some color)
Abstract
Helicobacter pylori (H. pylori) infection has received tremendous attention due to
its progressive injury to the gastric mucosa with a high risk for gastrointestinal diseases
such as asymptomatic chronic gastritis, peptic ulcer, and even gastric cancer. H. pylori
can create the mucin de-gel and transform their shapes based on the microenvironment
so that they could get into the mucus layer easily and thrive in the stomach. However,
without the specific characteristics of the bacteria, some pharmaceutical ingredients can
hardly reach the lining of the stomach where H. pylori colonize due to the harsh gastric
acid environment and the mucosa with high viscosity and elasticity. Considering the
increasing prevalence of H. pylori and the high fatality of resulting gastric cancer, finding
a mo...[
Read more ]
Helicobacter pylori (H. pylori) infection has received tremendous attention due to
its progressive injury to the gastric mucosa with a high risk for gastrointestinal diseases
such as asymptomatic chronic gastritis, peptic ulcer, and even gastric cancer. H. pylori
can create the mucin de-gel and transform their shapes based on the microenvironment
so that they could get into the mucus layer easily and thrive in the stomach. However,
without the specific characteristics of the bacteria, some pharmaceutical ingredients can
hardly reach the lining of the stomach where H. pylori colonize due to the harsh gastric
acid environment and the mucosa with high viscosity and elasticity. Considering the
increasing prevalence of H. pylori and the high fatality of resulting gastric cancer, finding
a more effective and efficient eradication therapy for H. pylori infection is a public
health priority.
In this thesis, we developed a MOF-based self-propelled micromotor as the modified
drug delivery system for H. pylori eradication treatment which could target at stomach
mucus layer where the bacteria thrive. The micromotor is composed of PEDOT/Au
shell, Zinc engine, R6G@ZIF-8-loaded gelatin and enteric coating. We utilized template electrodeposition method for synthesizing the PEDOT/Au shell and Zn segment.
R6G as the model drug was encapsulated by ZIF-8-loaded gelatin and infiltrated
into the micromotor for sustainable release. And the enteric polymer was then added at
the drug side for the hermetic seal.
Once administered, the self-propelled micromotors could propel themselves by
generating hydrogen bubbles and the propulsion velocity could reach 60 μm/s. During
the propulsion, the model drug in the motor was well-protected from the strong gastric
acid with the enteric coating. When they penetrated the firm mucus layer (pH > 6), the
enteric cap dissolved and enabled the target drug to be released efficiently. With the
high surface area and loading capacity of ZIF-8 particles, the model drug@ZIF-8
showed a flatter release curve and greatly prolonged body retention time (from 12 h to
over 2 weeks). The drug capacity and propulsion lifetime can be tuned by adjusting the
compartment length. The morphology and compartment distribution have been characterized.
The results in vitro showed that the self-propelled micromotor could greatly
increase the cell uptake rate (95.8%) compared with the bare model drug (9.3%) with a
150 μm-thick artificial mucus layer. At last, the micromotors were proved to have good
biocompatibility and low cytotoxicity (19 μg/ml at cell level). Overall, the proposed
MOF-based self-propelled micromotor provides a modified strategy for active transport
and targeted drug delivery with sustainable release. It holds considerable promise for a
wide range of future applications, including H. pylori, diabetes treatment and oral drug
delivery of biomacromolecules.
Post a Comment