Sweetening Drug Delivery for Future Therapies: Hydrogels Based on Sugars for Biomedical Applications
Lead Research Organisation:
University of East Anglia
Department Name: Pharmacy
Abstract
Hydrogels are 3D, cross-linked networks of water-soluble polymers, and formulated in a variety of physical forms (slabs, microparticles, nanoparticles...). Hydrogels show great promise in biomedical applications, drug delivery in particular, but also in clinical practice and experimental medicine for a wide range of applications (tissue engineering, regenerative medicine, diagnostics, cellular immobilization, separation of biomolecules or cells). Within the broad chemical family of "sugars", polysaccharides are excellent biopolymers for hydrogel preparation in biomedical contexts: they are non-toxic, water-soluble with high capability for swelling induced by simple chemical modifications, and they can be biodegraded to nontoxic products that are easily assimilated by the body. Great advances in polymer preparation for hydrogels (enzymatic procedures, nanocomposites, etc.) needs to be followed by an understanding at molecular level of the processes of gelation, the role of water, and the impact on final performance. In this project we will use state-of-the-art NMR spectroscopy (solution, solid, and gel state advanced experiments) to deepen our understanding of the molecular details of novel hydrogel materials based on starch and nanocellulose fibres. We will use cutting-edge glycobiology techniques (enzymatic and click chemistry) for functionalisation of nanocrystalline cellulose, prepare advanced materials (nanocomposite and interpenetrating network hydrogels), and will develop novel NMR spectroscopic protocols to understand the structure and dynamics of the biomaterials.
Organisations
Publications
Nigmatullin R
(2018)
Mechanically Robust Gels Formed from Hydrophobized Cellulose Nanocrystals.
in ACS applied materials & interfaces
Nigmatullin R
(2020)
Hydrophobization of Cellulose Nanocrystals for Aqueous Colloidal Suspensions and Gels.
in Biomacromolecules
Muñoz-García JC
(2019)
High Molecular Weight Mixed-Linkage Glucan as a Mechanical and Hydration Modulator of Bacterial Cellulose: Characterization by Advanced NMR Spectroscopy.
in Biomacromolecules
Nigmatullin R
(2019)
Thermosensitive supramolecular and colloidal hydrogels via self-assembly modulated by hydrophobized cellulose nanocrystals
in Cellulose
De Andrade P
(2021)
Chemoenzymatic Synthesis of Fluorinated Cellodextrins Identifies a New Allomorph for Cellulose-Like Materials*.
in Chemistry (Weinheim an der Bergstrasse, Germany)
Invernizzi C
(2020)
Non-invasive mobile technology to study the stratigraphy of ancient Cremonese violins: OCT, NMR-MOUSE, XRF and reflection FT-IR spectroscopy
in Microchemical Journal
Calabrese V
(2018)
Surfactant controlled zwitterionic cellulose nanofibril dispersions.
in Soft matter
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011216/1 | 01/10/2015 | 31/03/2024 | |||
| 1777178 | Studentship | BB/M011216/1 | 01/10/2016 | 30/09/2020 | Valeria Gabrielli |
| Description | Hydrogels are formed by a three-dimensional cross-linked networks of water-soluble polymers and they can be formulated in a variety of physical forms. Due to the high water content, they show great interest as drug delivery systems for local therapy, such as regenerative medicine, as well as in clinical practice and experimental medicine (tissue engineering, diagnostics, cellular immobilization, separation of biomolecules or cells). Among the various possible components, polysaccharides are excellent biopolymers for hydrogel preparation as they are no-toxic, water-soluble, and biodegradable into nontoxic products which are easily assimilated by the body. Although the high interest on this field from both an academic and industrial prospective, a complete understanding of the gelation and an atomic-detailed knowledge of the role of water in the molecular self-assembly processes is still needed. We have been developing STD NMR based protocols for the understanding the performance of polysaccharide based hydrogels, taking into account the high heterogeneity of those systems. The properties of carbohydrate based hydrogel can be tailored by the introduction of functional group which would give, for example, pH and temperature responsiveness. Cellulose is the most abundant polysaccharide in the world and it has been for long used in the pharmaceutical and food industry. Unfortunately, the functional modification on cellulose via conventional organic synthesis is laborious and requires harsh conditions. On the other hand, the enzymatic synthesis of short cellodextrin chains via Cellodextrin Phosphorylase has been proved to be an effective way to obtain show cello-oligosaccharides chains with functional groups introduced in a regio- and stereo-selective way. The success of the reaction depends on the enzyme permissiveness towards non-natural substrates. Part of the research funded by this award was focused in the investigation of the binding of difference CDP substrates employing a combination of solution state NMR methodologies and molecular docking. The regions of contact between the substrates and the enzyme were revealed, indicating hot spots for substrate recognition. In addition, 3D models still unavailable so far were generated. In addition, Cellodextrin Phosphorylase was used for the synthesis a series of site selectively fluorinated cellodextrins of different degrees of fluorination and substitution patterns by chemoenzymatic synthesis. Thanks to the scientific consortium established within the John Innes Centre, the University of East Anglia and the University of Bristol, we combined microscopy (TEM and AFM), Raman spectroscopy, PXRD and advanced NMR spectroscopy to obtain structural characterisation at different length scales (morphological, long range and short range structural information). In specific, we combined solution and solid state NMR approaches to achieve a full assignment of this new materials characterised by different ordered and disordered domains. |
| Exploitation Route | This research shows both academic and non-academic applicability. From an academic prospective, the establishment of new NMR methodologies for the study of hydrogels enhance the understanding of the gelation mechanisms. In addition, the development of novel material with tailored and stimuli-triggered properties and biomedical applications will definitively be of interest for industrial purposes. The CDP study opens the door for the rational enzyme engineering with the aim of expanding the enzyme permissiveness. This will allow the enzymatic synthesis of novel cello-oligosaccharides based material. The CDP study opens the door for the rational enzyme engineering with the aim of expanding the enzyme permissiveness. This will allow the enzymatic synthesis of novel cello-oligosaccharides based material. |
| Sectors | Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |