Tailor-made biofunctionalized nanoparticles using layer-by-layer technology

Abstract

Layer-by-layer (LBL) technique is a well-established method for the formation of nanofilms on planar surfaces, as well as on micro-sized colloidal particles. For surface functionalization of nanoparticles, it is a very recent area of research receiving great interest due to the advantage of obtaining fine control over the shell composition, charge and thickness, offering several applications in pharmaceutical and biomedical fields. This article provides an overview of the recent achievements in application of this technology on nanoparticles and their potential applications. Future research directions are also discussed.

Introduction

Nanotechnology, or more appropriately nanoscience, is a multidisciplinary branch of science that currently receives enormous efforts of scientists and researchers. Several definitions for nanotechnology were provided by researchers and institutions:

• A practical definition of nanotechnology is “the design, characterization, production, and application of structures, devices, and systems by controlled manipulation of size and shape at the nanometer scale (atomic, molecular, and macromolecular scale) that produces structures, devices, and systems with at least one novel/superior characteristic or property” (Koo et al., 2005).

• The National Nanotechnology Initiative (NNI), on the other hand, defined nanotechnology as the “understanding and control of matter at dimensions of roughly 1–100 nm, where unique phenomena enable novel applications” (Bawa et al., 2005).

Both definitions are aiming towards the control of objects at the nanometer scale but in slightly different size ranges. Advances in nanoscience are spurring a revolution in the future of pharmaceutical and biomedical fields, in which the application of nanotechnology has provided new avenues for engineering materials with molecular precision allowing for fabricating nanoscale delivery devices that integrate molecular recognition and site-specific delivery. In addition to controlled drug release and drug targeting, nanodelivery systems could offer protection and improve the pharmacokinetics of easily degradable peptides and proteins, which often have short half-lives in vivo. A growing number of therapeutic compounds currently being developed by pharmaceutical companies are poorly water soluble leading to limited and/or erratic bioavailability. Nanoparticle formation has been exploited as a method to improve the bioavailability of these poorly water-soluble active pharmaceutical ingredients. In addition, nanotechnology applications in gene delivery and tissue engineering are of high interest (Bawarski et al., 2008).

The rapid development of nanotechnology and nanomaterials has led to a need for engineering the surface properties of nanoparticles for a variety of applications. Coating of nanoparticles changes the physicochemical parameters of the nanoparticles through altering the charge, functionalities and reactivity of the surface. The impetus for coating nanoparticles was not only to improve the colloidal stability in biological fluids and extend the half-life of the nanoparticulate formulations inside the body but also to tailor the surface to specific physical, optical, electronic, chemical and biomedical properties using wide varieties of coating materials. Almost all types of nanoparticles were subjected to coating, including lipid (Cui and Mumper, 2002), polymeric (Sheng et al., 2009) and inorganic (Aqil et al., 2008, Neumann et al., 2009) nanoparticles. The surface of nanoparticles was modified with biomolecules such as proteins (Cui and Mumper, 2002, Ogawara et al., 2004) and DNA (Neumann et al., 2009) as well as polymeric (Acar et al., 2005, Gu et al., 2007, Aqil et al., 2008, Sheng et al., 2009), inorganic (Mine et al., 2003, Dang et al., 2010) and lipid (Zhang et al., 2006, Li et al., 2008a) materials. The methods used for coating of nanoparticles are mainly based on chemical methods, thus differ from one case to another depending on the core chemistry and physical properties. The layer-by-layer (LBL) deposition of polyelectrolytes depending on electrostatic self-assembly was therefore a significant innovation allowing for the development of an easy standard method for the surface functionalization of a broad range of nanoparticles. A key advantage of this technique is the preparation of nanoparticles of core-independent but shell-dependant characteristics. This would result in nanoparticles of different sizes suitable for targeting different sites in the body depending on the site-specific needs. In addition, studies based on investigating the effect of size and surface chemistry of a single nanosystem would be thus feasible.

LBL deposition of polyelectrolytes on planar surfaces or micro- or submicroparticles has been the focus of several reviews (Caruso, 2001, Gittins and Caruso, 2001, Antipov and Sukhorukov, 2004, Shchukin and Sukhorukov, 2004, Johnston et al., 2006, Gil et al., 2008). However, coating of nanoparticles, of size less than or around 100 nm with polyelectrolytes using LBL technique is a more recent approach. The main objective of this review is thus to shed light on the potential of pharmaceutical and biomedical applications for core/shell nanoparticles, prepared by layer-by-layer technique, with special emphasis on using gold nanoparticles (AuNP) as the most often utilized template for subsequent layering. However, other nanoparticulate templates are also highlighted.