Hydrogels And Nanogels Applications In Medicine

Author : Yingkai Liang
Publisher :
ISBN 13 : 9781369351644
Total Pages : 171 pages
Book Rating : 4.3/5 (516 download)

DOWNLOAD NOW!

Download or read book Engineering Polymeric Matrices for Controlled Drug Delivery Applications written by Yingkai Liang and published by . This book was released on 2016 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past few decades, drug delivery systems have been designed using a wide array of materials and chemical strategies to improve the specificity of therapeutics by increasing drug stabilities, controlling release profiles and localizing therapeutic effects. Among various types of drug delivery systems, hydrogels have emerged as a promising class of materials for the controlled release of bioactive molecules. Composed of hydrophilic three-dimensional polymer networks, hydrogels have several advantageous properties including high water content, tunable viscoelasticity, and biocompatibility, which allow bioactive molecules to be protected against degradation and released from the hydrogel matrix in a controlled manner over an extended period of time. Particularly, polyethylene glycol (PEG) hydrogels have been extensively used for controlled drug delivery applications with encouraging preclinical and clinical results, owing to the non-immunogenic nature, hydrophilicity and chemical versatility of PEG polymers. PEG hydrogel-based materials have received approval for use in a number of medical products including wound healing matrices, medical implants, and drug delivery depots. In this work, we have specifically engineered PEG hydrogel matrices from bulk to nanoscale, including bulk hydrogels, nanoparticle-crosslinked hybrid hydrogels and nanogels for different delivery applications. Firstly, a library of hydrophilic and hydrolytically degradable PEG hydrogels has been developed for the sustained delivery of an anthrax toxin-neutralizing monoclonal antibody from 14-56 days. The hydrogels were formed via a Michael-type addition between multi-arm PEG-SH and hydrolytically degradable crosslinkers of linear PEG-diacrylate. By varying the polymer architectures and molecular weights of the precursors, the degradation rate of the matrix can be systematically tuned, which in turn tailors the rate of antibody release from the hydrogels. In-gel and post-release analysis of the antibody samples indicate that the conformational properties and biological activity of the protein were well maintained. In addition to bulk hydrogels for the long-term delivery of therapeutics, stimuliresponsive, nanoparticle-crosslinked hybrid hydrogels have also been introduced for the triggered and targeted release of therapeutic molecules. These hybrid hydrogels were constructed using maleimide-functionalized liposomes (~100nm) as structural elements to crosslink with thiolated 4-arm PEG polymers via Michael-type addition. Degradation of these hydrogels was selectively triggered upon exposure to thiol-containing molecules such as glutathione (GSH), offering great advantages for controlled and triggered release of therapeutic cargos under reducing environments that are analogous to the GSH-overproduced tumor microenvironment. The hierarchical structure of these hybrid hydrogels allows dual encapsulation and prolonged, sequential delivery of multiple therapeutic molecules with different release mechanism. Motivated by the significant impact of nanotechnology on the development of nanoscale drug delivery vehicles, PEG nanogels that combine the advantages of both nanoparticulate and polymeric hydrogel systems were prepared via the use of liposome templates. The nanogels were formed by photo-triggered Michael-type addition of PEG polymer precursors encapsulated within the aqeuous lumen of liposomes under UV irradiation. The production of nanogels was confirmed via dynamic light scattering (DLS) and transmission electron microscopy (TEM). The surface functionality of the lipid-coated nanogels was demonstrated by surface modification with a reactive fluorescent dye as a proof of concept. These PEG-based polymeric matrices provide a powerful platform for different specific delivery applications. The bulk, hydrolytically degradable PEG hydrogels present a simple yet efficient strategy to provide protein stabilization and long-term delivery of therapeutic proteins. The liposome-crosslinked hybrid hydrogels, on the other hand, suggest significant potential in the triggered and temporal release of multiple therapeutic molecules. Lastly, the PEG nanogels offer a unique strategy for the development of multifunctional nanoparticle therapeutics.