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Title: Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles
Authors: Pakulska, Malgosia M.
Elliott Donaghue, Irja
Obermeyer, Jaclyn M.
Tuladhar, Anup
McLaughlin, Christopher K.
Shendruk, Tyler N.
Shoichet, Molly S.
Issue Date: 2016
Publisher: © The Authors, some rights reserved. Published by American Association for the Advancement of Science
Citation: PAKULSKA, M.M. ... et al., 2016. Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. Science Advances, 2(5): e1600519.
Abstract: 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.
Description: This is an Open Access Article. It is published by American Association for the Advancement of Science under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) licence. Full details of this licence are available at: http://creativecommons.org/licenses/by-nc/4.0/
Sponsor: We received funding from the Canadian Institutes of Health Research [foundation grant to M.S.S. (FDN143276) and Training program in regenerative medicine scholarship to A.T.], the Natural Sciences and Engineering Research Council of Canada (NSERC) [Discovery (RGPIN-2014-04679) to M.S.S., Vanier to M.M.P., post-doctoral fellowship to C.K.M., Canada graduate scholarship - doctoral program to J.M.O., and post-graduate scholarship - doctoral program and NSERC Collaborative Research and Training Experience Program in M3 Materials, Mimetics, and Manufacturing (CREAT 432258-13) to I.E.D.], Ontario Graduate Scholarship (to M.M.P.), the Canadian Partnership in Stroke Recovery (A.T. and M.S.S.), the Heart and Stroke Foundation of Canada (000170 to M.S.S.), the European Molecular Biology Organization (ALTF181-2013 to T.N.S.), and the European Research Council (Advanced Grant MiCE 291234 to T.N.S.).
Version: Published
DOI: 10.1126/sciadv.1600519
URI: https://dspace.lboro.ac.uk/2134/36378
Publisher Link: https://doi.org/10.1126/sciadv.1600519
Appears in Collections:Published Articles (Maths)

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