Layer-by-layer engineered capsules and their applications

Abstract

Over the last 15 years, development of the layer-by-layer (LbL) technique for preparing thin films has greatly improved control over the physical and chemical properties of thin films. When applied to colloidal particles, the LbL technology permits the formation of hollow capsules with engineered features, including size, shape, composition and function. In this review, we outline the potential applications of LbL assembled micro- and nanometer-sized capsules. These lie principally in the areas of drug delivery, sensing, catalysis and microreactors. We focus on the potential use of LbL capsules as drug delivery vehicles and, specifically, on methods for encapsulating and releasing molecules from capsules as well as on targeting capsules to cells.

Introduction

Micro- and nanometer-sized capsules have found application in diverse areas, ranging from medicine and biotechnology to catalysis and synthetic chemistry. Since their introduction in 1998 [1], [2], capsules prepared via the layer-by-layer (LbL) technique [3] have attracted particular interest, largely because of the ability to readily tailor their properties (e.g., size, composition, porosity, stability, surface functionality, colloidal stability). In addition, the step-wise formation of these capsules allows the introduction of multiple functionalities, thus providing opportunities to engineer a new class of materials with unprecedented structure and function. For example, LbL capsules can be assembled from a suite of materials, including synthetic and natural polyelectrolytes, nanoparticles and biomacromolecules [4^••]. A range of colloidal particles with sizes varying from nanometers to many micrometers, and composition spanning inorganic and polymer particles to those composed of biomacromolecules or low molecular weight species, can be used as the particle templates [4••], [5]. The capsule surface can be modified to alter the functionality and/or improve the colloidal stability of the capsules, and various materials can be sequestered into the capsule interior for drug delivery, sensing or catalysis applications.

LbL capsules are typically formed by the consecutive deposition of complementary/interacting polymers onto colloidal particles, followed by removal of the sacrificial colloidal template (Fig. 1) [4••], [5]. A large number of inorganic [2], [6] and polymer-based capsules assembled by the LbL method have been reported. In this review, we will focus on capsules prepared from polyelectrolytes, as the vast majority of capsules have been assembled by the alternate deposition of positively and negatively charged polymers, where electrostatic forces facilitate layer build-up. LbL assembly has been extended to films held together by hydrogen bonding [7], [8], hydrophobic interactions [9] and, more recently, hybridization of DNA base pairs [10], [11]. The latter approach has led to LbL capsules composed entirely of DNA with designed composition, structure and stability [10], [11]. Varying the layer number, the assembly conditions (e.g., salt concentration, pH) [12], [13] and the multilayer composition [14], [15] readily affords control over the properties of polyelectrolyte capsules.

In this review, we focus on the preparation and application of polyelectrolyte capsules as drug delivery vehicles, with particular emphasis on developments made in recent years. The principal advantage of capsule-based delivery vehicles [16] is that the capsule protects both the drug from degradation by the body and the body from side effects of the drug. For micro-/nanocapsules to have application as therapeutic delivery vehicles, three areas must be addressed: (i) encapsulation of the therapeutic, (ii) targeting of the capsules in biological systems and (iii) release of the therapeutic from the capsules. The different strategies used to encapsulate materials within LbL capsules will be addressed. The importance and potential of such capsules to target cells will be highlighted, and recent advances in releasing such materials from LbL capsules will be discussed. Additionally, the use of capsules in sensing applications will be briefly discussed.