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  • 1
    Publication Date: 2016-03-19
    Description: Exploiting binding affinities between molecules is an established practice in many fields, including biochemical separations, diagnostics, and drug development; however, using these affinities to control biomolecule release is a more recent strategy. Affinity-controlled release takes advantage of the reversible nature of noncovalent interactions between a therapeutic protein and a binding partner to slow the diffusive release of the protein from a vehicle. This process, in contrast to degradation-controlled sustained-release formulations such as poly(lactic-co-glycolic acid) microspheres, is controlled through the strength of the binding interaction, the binding kinetics, and the concentration of binding partners. In the context of affinity-controlled release--and specifically the discovery or design of binding partners--we review advances in in vitro selection and directed evolution of proteins, peptides, and oligonucleotides (aptamers), aided by computational design.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pakulska, Malgosia M -- Miersch, Shane -- Shoichet, Molly S -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):aac4750. doi: 10.1126/science.aac4750.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. ; Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, and Donnelly Centre, University of Toronto, Toronto, Ontario, Canada. Department of Chemistry, University of Toronto, Toronto, Ontario, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989257" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Engineering ; Combinatorial Chemistry Techniques ; Delayed-Action Preparations/*chemistry ; Directed Molecular Evolution ; *Drug Design ; Humans ; Lactic Acid/*chemistry ; Microspheres ; Polyglycolic Acid/*chemistry ; Proteins/*administration & dosage
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2016-05-28
    Description: Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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