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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.
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.).|
|Publisher Link: ||https://doi.org/10.1126/sciadv.1600519|
|Appears in Collections:||Published Articles (Maths)|
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