Protein-based nanocarriers as promising drug and gene delivery systems

Abstract

Among the available potential colloidal drug carrier systems, protein-based nanocarriers are particularly interesting. Meeting requirements such as low cytotoxicity, abundant renewable sources, high drug binding capacity and significant uptake into the targeted cells, protein-based nanocarriers represent promising candidates for efficient drug and gene delivery. Moreover, the unique protein structure offers the possibility of site-specific drug conjugation and targeting using various ligands modifying the surface of protein nanocarriers. The current review highlights the main advances achieved in utilizing protein nanocarriers as natural vehicles for drug and gene delivery tasks with respect to types, advantages, limitations, formulation aspects as well as the major outcomes of the in vitro and in vivo investigations. The recently emerged technologies in the formulation of protein nanocarriers including using recombinant proteins as alternatives to native ones and new non-toxic crosslinkers as alternatives to the toxic chemical crosslinkers are also discussed.

Introduction

In recent years, there has been a considerable interest in the development of novel drug delivery systems using nanotechnology [1], [2]. Polymeric materials used for preparing nanoparticles for drug delivery must be at least biocompatible and best biodegradable. The use of natural polymers has been very well described in the literature for fabrication of nanoparticles [3], [4]. Obviously, there is growing interest in developing protein nanocarriers as GRAS (generally regarded as safe) drug delivery devices due to their exceptional characteristics, namely biodegradability, nonantigenicity, high nutritional value, abundant renewable sources and extraordinary binding capacity of various drugs. Proteins have the possibility of less opsonization by the reticuloendothelial system (RES) through an aqueous steric barrier in addition to their excellent functional properties including emulsification, gelation, foaming and water binding capacity [5], [6], [7]. Moreover, protein nanoparticles can be easily prepared and scaled up during manufacture [6], [7].

Owing to multiple functional groups in the primary sequences of polypeptides, protein nanoparticles can be exploited to create different interactions with therapeutic compounds and subsequently form three-dimensional networks offering a variety of possibilities for reversible binding of active molecules, protecting them in a matrix as well as specific targeting to the site of action [6], [7]. Furthermore, protein nanoparticles possess acceptability as metabolizable naturally occurring components. Hydrolysis of proteins by digestive enzymes generates bioactive peptides that may exert a number of physiological effects in vivo [5]. This review embodies an in-depth discussion of the nanoparticulate drug delivery systems that make use of proteins as drug carriers.