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Multifunctional supramolecular hydrogels as biomaterials

A technology of supramolecular hydrogels and functional molecules, applied in the field of multifunctional supramolecular hydrogels as biological materials, can solve the problems of single function and high cost

Inactive Publication Date: 2009-05-13
THE HONG KONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these oligopeptide-based hydrogels are only monofunctional, and their cost remains high

Method used

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  • Multifunctional supramolecular hydrogels as biomaterials
  • Multifunctional supramolecular hydrogels as biomaterials
  • Multifunctional supramolecular hydrogels as biomaterials

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1. Wound Healing

[0049] In order to illustrate the biological activity of the supramolecular hydrogel of the present invention, it contains such as figure 1 Hydrogels of the functional molecules shown were used to treat uranium wounds by abrading the skin on the backs of mice and administering uranyl nitrate superficially to the wounds. Then, the hydrogel was then topically administered for 20 minutes on the wound of the negative control group, but not the positive control group. The result of the experiment is as figure 2 As shown in A. Mice in all groups showed a loss of original body weight on the second day due to the effect of trauma. The negative control group healed the wound quickly after experiencing a slight loss of original body weight and returned to normal growth the next day. In contrast, the positive control group exhibited sustained weight loss until death at about day 5 or a 35% weight loss over the next ten days. Thus, when the hydrog...

Embodiment 2

[0052] Example 2. Non-covalently cross-linked supramolecular hydrogels

[0053] While in situ polymerization allows for enhanced stability of small molecule gels, such methods of covalent crosslinking typically require additional chemical synthesis, which alters the properties of the hydrogelator and may lead to loss of biocompatibility and Biodegradability. Therefore, it is preferable to use molecular recognition (non-covalent cross-linking) to enhance the elasticity of small molecule hydrogels. For example, addition of ligands to mechanically poor hydrogels of receptor derivatives resulted in up to a million-fold increase in the hydrogel storage modulus. The term "non-covalent crosslinking" means that the crosslinking is achieved by hydrogen bonding, hydrophobic forces or ionic forces.

[0054] In one embodiment, vancomycin (Van) was chosen as ligand 4 and D-Ala-D-Ala derivative was chosen as receptor 5 because of the well established molecules between 4 and 5 in aqueous...

Embodiment 3

[0057] Example 3. Antibiotic Supramolecular Hydrogel

[0058] Figure 4A The chemical structure of 8 is shown (when R = pyrenyl), Figure 4B A photograph showing the formation of a hydrogel by adding 6.5 mg of 8 to 1.8 ml of water corresponds to ~0.36 wt% (2.2 mM) gelator and ~23000 water molecules / gelator molecule. 8 Unexpectedly potent (0.125-2μg / ml, 8-11 times lower dilution than the corresponding vancomycin), inhibiting VRE (2 vanA-positive Enterococcus faecalis, 4 vanA-positive Streptococcus faecalis, 4 vanB-positive Enterococci). The strong propensity and unexpected potency of 8 for self-assembly also led us to speculate that 8 may aggregate into supramolecular structures at the cell surface when its local concentration is high.

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Abstract

The present invention pertains to the design and application of a supramolecular hydrogel having a three-dimensional, selfassembling, elastic, network structure comprising non-polymeric, functional molecules and a liquid medium, whereby the functional molecules are noncovalently crosslinked. The functional molecules may be, for instance, anti-inflammatory molecules, antibiotics, metal chelators, anticancer agents, small peptides, surface-modified nanoparticles, or a combination thereof. The design of the hydrogel includes: 1) modifying functional molecules to convert them into hydrogelators while enhancing or maintaining their therapeutic properties and 2) triggering -the hydrogelation process by physical, chemical, or enzymatic processes, thereby resulting in the creation of a supramolecular hydrogel via formation of non-covalent crosslinks by the functional molecules. Applications of the present invention include use of the supramolecular hydrogel, for instance, as a biomaterial for wound healing, tissue engineering, drug delivery, and drug / inhibitor screening.

Description

technical field [0001] This application claims the benefit of US Serial No. 60 / 613,413 filed September 28, 2004, the contents of which are hereby incorporated by reference in their entirety. [0002] Throughout this application, various references are cited and the disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains. Background technique [0003] Hydrogels formed from three-dimensional, elastic networks whose interstitial spaces are filled with liquid have various useful properties (eg, response to external stimuli, flow to accommodate shear forces, etc.). Because of their useful properties, hydrogels have been applied in many fields such as bioanalysis, chemical sensing, food processing, cosmetics, drug delivery and tissue engineering. [0004] After the successful application of polymer-based hydrogels in biomedical engineering...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/14
CPCA61L2300/802A61L2300/624A61K47/48784A61K31/7034A61K38/05A61K9/0009A61L2300/41B82Y5/00A61K9/0014A61K9/06A61L2300/252A61K47/34A61K31/43A61L2300/404A61L27/52A61K47/183A61L2300/416A61L27/54A61K31/545A61K31/7048A61K47/48961A61K47/6903A61K47/6949
Inventor 徐兵杨志谋徐克明
Owner THE HONG KONG UNIV OF SCI & TECH
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