Two chemical methods, multi-reducing end modification and bleach oxidation, were used to prepare polysaccharide aldehydes and ketones. Their derived hydrogels and microgels were made for potential drug-delivery applications.
Polysaccharide aldehydes and ketones are reactive intermediates for adding other functional moieties through chemo selective reactions such as Schiff-base formation or reductive amination. The most widely used method to prepare polysaccharide aldehydes is periodate oxidation. However, this method impacts higher-order polysaccharide structure, decreases degree of polymerization (DP), and increases polysaccharide instability, leading to degraded mechanical properties. Developing a new method to prepare polysaccharide aldehydes while preserving DP, stability, and desirable physical properties is challenging. Inspired by the reactive reducing ends of polysaccharides, which are the anomeric carbons (at the chain end), one per natural polysaccharide molecule, that (for aldose-based polysaccharides) is in equilibrium between a ring-closed hemiacetal and an open-chain aldehyde form, we developed a novel method to prepare polysaccharide aldehydes by attaching monosaccharides to polysaccharide chains. Herein, we describe the approach of attachment through amination between amine group at the C2 position of the monosaccharide and carboxylic acid groups on polysaccharides. In this way, more reducing ends (C1 of the monosaccharide) can be introduced to the polysaccharides. We have chosen to call this new family of polysaccharides "multi-reducing end polysaccharides (MREPs)". We call this method "multi-reducing end modification".
We then fabricated injectable, self-healing, fast gelling Schiff base hydrogels based on MREPs. Previous methods to fabricate Schiff base polysaccharide hydrogels usually required periodate oxidation which leads to degraded mechanical properties, with gelation time typically from minutes to hours. We employed acetic acid to induce fast gelation of our MREPs hydrogels within seconds. The Schiff base MREP hydrogels exhibited self-healing and injectable behavior with limited cytotoxicity, which is promising for future biomedical applications such as targeted drug delivery or tissue engineering.
Microgels are dispersible but undissolvable colloids of three-dimensional polymer networks with numerous applications. We synthesized all-polysaccharide microgels (herein, we use the general term "microgels" to describe small gel particles of nanometer to micron diameters) using oxidized hydroxypropyl cellulose (Ox-HPC), carboxymethyl chitosan (CMCS), and calcium chloride. By tuning the calcium concentration, uniform microgels can be obtained with gel size in the hundreds of nanometers. Model amine-containing drugs such as picloram or p-aminobenzoic acid (pABA) can be chemically attached to Ox-HPC through Schiff base chemistry, creating imine bonds that are reversible in water, thereby permitting slow release. This class of all-polysaccharide microgels showed promising applications in agriculture, such as controlled release of agrochemicals.
We anticipated that these strategies would benefit future polysaccharide chemistry research and permit synthesis of novel hydrogel or microgel systems with potential drug-delivery applications. / Doctor of Philosophy / Polysaccharides are long chains composed of sugar units ("sugar polymers"). Many natural-derived polysaccharides are sustainable, biodegradable and have low toxicity. Hydrogels are composed of porous solids and water, similar to the structure of human tissues. "Microgels" are used herein to describe small gels of nanometer to micron diameters. Fabrication of polysaccharides into hydrogels or microgels can be advantageous for drug-delivery applications.
Chemical modification of polysaccharides is usually required before making polysaccharide-based hydrogels or microgels. However, previously described methods usually destroy the chemical structure of polysaccharides and cause degradation. To overcome this challenge, we developed a non-destructive chemical modification method to prepare hydrogels without these disadvantages. This method also introduced a new concept in polysaccharide science.
Following our novel chemical modification method, polysaccharide-based hydrogels were made. Compared to the previous polysaccharide hydrogels which usually required long gelation times, our polysaccharide hydrogels gel within seconds with addition of tiny amounts of vinegar. Besides, our polysaccharide-based hydrogels are injectable and spontaneously repair themselves with low toxicity to cells. These properties make our hydrogels promising for cancer-targeted drug delivery.
Food is the first necessity of human beings. Pesticides are often used in excessive amounts and in broad distribution, to guarantee high crop productivity. Excess use and/or distribution of pesticides can pollute to the environment and pose threats to human health. To solve this problem, we made all polysaccharide microgels, dispersed in benign water, that can permit slow release of pesticides, applied in a form that can promote great precision.
Overall, we developed new ways to modify polysaccharides to create effective and harmless hydrogels or microgels. We aim to push the boundaries of science and benefit human society through our research.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/120984 |
| Date | 21 August 2024 |
| Creators | Zhai, Zhenghao |
| Contributors | Graduate School, Edgar, Kevin J., Johnson, Blake, Roman, Maren, Matson, John, Frazier, Charles E. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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