DOI: 10.1021/la104232r 1275 Langmuir 2011, 27(4), 1275–1280 Published on Web 12/03/2010 pubs.acs.org/Langmuir © 2010 American Chemical Society Modular Assembly of Layer-by-Layer Capsules with Tailored Degradation Profiles † Christopher J. Ochs, Georgina K. Such, and Frank Caruso* Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia Received October 21, 2010. Revised Manuscript Received November 8, 2010 Herein we report the preparation of layer-by-layer (LbL) assembled, biodegradable, covalently stabilized capsules with tunable degradation properties. Poly(L-glutamic acid) modified with alkyne moieties (PGA Alk ) was alternately assembled with poly(N-vinyl pyrrolidone) (PVPON) on silica particles via hydrogen-bonding. The films were cross- linked with a bis-azide linker, followed by removal of the sacrificial template and PVPON at physiological pH through hydrogen bond disruption, yielding one-component PGA Alk capsules. To control the kinetics and location of capsule degradation, a number of approaches were investigated. First, a degradable bis-azide cross-linker was incorporated into the inherently enzymatically degradable capsules. Second, we assembled low-fouling capsules composed of nondegrad- able poly(N-vinyl pyrrolidone-ran-propargyl acrylate) (PVPON Alk ) via hydrogen bonding with poly(methacrylic acid) (PMA) and combined this with the aforementioned system (PGA Alk /PVPON) to produce stratified hybrid capsules. The degradation profiles of these stratified capsules can be closely controlled by the number as well as the position of nondegradable barrier layers in the systems. The facile tailoring of the degradation kinetics makes this stratified LbL approach promising for the design of tailored drug-delivery vehicles. Introduction The development of functional and engineered therapeutic carrier systems has received considerable and widespread interest over the past decade. A range of polymeric carriers have been developed for delivery applications, including polymersomes, micelles, and polymer capsules. 1-6 In particular, hollow polymer capsules prepared via layer-by-layer (LbL) assembly are of interest because they can be designed with a range of properties, such as enzymatic degradability, 7-9 low-fouling surface pro- perties, 10,11 and antibody functionalization for targeted drug delivery. 12-15 LbL capsules have been assembled from a variety of polymers based on electrostatic interactions, 16,17 hydrogen bonding, 18,19 and click chemistry. 20 Previous work has demon- strated that a range of properties can be engineered into LbL capsules to achieve cargo release in response to external triggers, such as optical or magnetic stimulation, 8,21-23 changes in pH, 20,24-27 or (enzymatic) degradation. 28-30 A common limitation of carrier systems is the initial burst release of the encapsulated cargo and the resulting rapid depletion of the drug reservoir. 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