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Polylactic Acid Sealed Polyelectrolyte Multilayer Microchambers for Entrapment of Salts and Small Hydrophilic Molecules Precipitates Meiyu Gai, Johannes Frueh, Valeriya L. Kudryavtseva, Alexey M. Yashchenok, and Gleb B. Sukhorukov ACS Appl. Mater. Interfaces, Just Accepted Manuscript • Publication Date (Web): 28 Apr 2017 Downloaded from http://pubs.acs.org on April 30, 2017
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ACS Applied Materials & Interfaces
Polylactic Acid Sealed Polyelectrolyte Multilayer Microchambers for Entrapment of Salts and Small Hydrophilic Molecules Precipitates Meiyu Gai§, Johannes Frueh†*, Valeriya L. Kudryavtseva‡, Alexey M. Yashchenok║, Gleb B. Sukhorukov§* †
State Key laboratory of Micro/Nano Technology Research Centre, Harbin Institute of
Technology, Yikuang Street 2, Harbin 150080, China. Email:
[email protected] §
School of Engineering and Materials Science, Queen Mary University of London, Mile End,
Eng, 215, London E1 4NS, United Kingdom. Email:
[email protected] ‡
National Research Tomsk Polytechnic University, RASA Center in Tomsk, Department of
Experimental Physics, Tomsk 634050, Russia ║
Remote Controlled Theranostic Systems Lab, Educational Research Institute of Nanostructures
and Biosystem, Saratov State University, 83 Astrakhanskaya Street, Saratov 410012, Russia
KEYWORDS:
Polyelectrolyte multilayer, hydrophobization, air bubble entrapment, small
hydrophilic molecules, controlled release, ultrasound, stimuli responsive
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ABSTRACT
Efficient depot systems for entrapment and storage of small water soluble molecules are of high demand for wide variety of applications ranging from implant based drug delivery in medicine and catalysis in chemical processes to anti-corrosive systems in industry where surface mediated active component delivery is required on time and site specific manner. This work reports the fabrication of individually sealed hollow-structured polyelectrolyte multilayer (PEM) microchamber arrays based on layer-by-layer self-assembly as scaffolds and microcontact printing. These PEM chambers are composed out of biocompatible polyelectrolytes and sealed by a monolayer of hydrophobic biocompatible and biodegradable polylactic acid (PLA). Coating the chambers with hydrophobic PLA allows for entrapment of a micro-air-bubble in each chamber that seals and hence drastically reduces the PEM permeability. PLA@PEM microchambers are proven to enable prolonged subaqueous storage of small hydrophilic salts and molecules such as crystalline NaCl, Doxicycline and fluorescent dye Rhodamine B. The presented microchambers are able to entrap air bubbles and demonstrate a novel strategy for entrapment, storage and protection of micropackaged water soluble substances in precipitated form. These chambers allow triggered release as demonstrated by ultrasound responsiveness of the chambers. Low frequency ultrasound exposure is utilized for microchamber opening and payload release.
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ACS Applied Materials & Interfaces
1. INTRODUCTION Nowadays the research community focuses particularly on layered polymer composite1 films to explore their potential and to harvest advantages in novel mechanical and diffusion barrier properties.2 Composite multi-functional materials are especially suitable in the fields of medical sciences (e.g. polymeric stent coatings) or anti-corrosion coatings.3–5 In these fields surface mechanical as well as hydrophilic properties are mandatory for surface mediated drug delivery and for diminishing thrombogenic properties of implants.3,6 The same properties are important to maximize adhesion for anti-corrosion systems.3,6 Encapsulation of precisely defined small quantities of hydrophilic active cargo requires hydrophobic diffusion barriers.7 Fabrication of such polymeric composite systems is commonly achieved via layered nano-deposition approaches based on electrostatic-, hydrogen bonding, as well as van-der-Waals interactions.8,9 The most versatile layered deposition system established to date are polyelectrolyte multilayers (PEM) based on layer-by-layer (LbL) self-assembly.10 While storage of polymeric or chemically linked drugs within the bulk of PEM is possible, a site specific release of precisely defined low quantities requires encapsulation within micro-chambers.7 The production of solid supported micro-containers with controlled encapsulation in micrometer sized arrays and stimuli responsive recovery potentials of small hydrophilic molecules remains a challenge.4,11–13 Such is, despite hitherto existing publications in the field of microcontainers and small molecule encapsulation for dispersed14 or adherent drug delivery systems.4,5,11,12
In
recent
years
polyelectrolyte
multilayers
(PEM)
motors,15,16
microcapsules10,17,18 and tubes19 were widely studied and utilized as microcontainer systems in drug delivery, but they failed to encapsulate hydrophilic cargos with low molecular weights due to capsule shell's high permeability.8,20 It has been shown that sealing small molecules (Mw ≤
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1000) was still a challenge even after increasing the PE monolayer number to 18.21 In addition, an increased shell thickness increases the difficulty of cargo encapsulation and release. Previously reported solid supported container arrays able to seal small water soluble dyes were on millimeter scale with 30-50 micrometer thick shells and required 1000 bilayers to withstand drying stress and avoid chamber collapse as well as to facilitate adequate sealing.12 Such systems are 1000 times too large for intra-corporal applications, sensor science and anticorrosive systems.11,22,23 Other silk based micro-chamber systems were produced via lithography but only able to encapsulate hydrophobic polymers.24 PEM based microcontainer arrays were introduced by Kiryukhin et al. and offered light stimuli-responsive release properties, however lacked the ability to encapsulate hydrophilic low-molecular-weight (
