Nanoparticles: Crossing barriers and membrane interactions

Abstract

In recent years, the field of nanotechnology has progressed at an exponential pace and is now at the forefront of medical research. Future nanomedicine (primarily the field of cancer nanotechnology) is projected to have an enormous impact on both diagnostics and treatment modalities to improve human health. Therefore, research and development of engineered multifunctional nanoparticles as imaging tools and pharmaceutical drug carriers is an area of current interest. The field of nanomedicine embraces a number of outstanding questions, critical for successful applications of nanoparticles in disease identification and cure. These include: (a) Technological developments to produce monodisperse drug-loaded nanocarriers, (b) biological factors affecting accumulation of nanocarriers to the diseased tissues including skin; (c) intracellular localization of nanoparticles via receptor-mediated targeting; (d) exploitation of the microenvironment of the tumour tissue for selective targeting of nanoparticles; (e) an understanding of molecular interactions between nanoparticles, biological membranes, intracellular organelles, preferred drug transport mechanisms; and finally (e) strategies for localized drug release intracellularly or in the vicinity of the tumours. It is our intention to address some of these issues in this special issue. Articles from experts in their respective research disciplines in nanomedicine are included to provide a broad overview of the current status of nanoparticle research. The papers present the latest information on the fabrication of nanoparticles, issues related to targeting, effect of route of administration, nano-imaging tools, and on-demand drug release. Each of these research fields provide excellent opportunities for cancer treatment, yet face limitations. The primary modes of nanoparticle delivery include intravenous, topical and oral administration. In either case, the ability of nanoparticles to cross barriers, such as the skin (topical delivery route) or GI tract (oral administration) or blood brain barrier (BBB) is a prerequisite for their success. It is important to understand the molecular mechanisms of nanoparticle-membrane interactions during multiple steps. Therefore the studies aimed at examining the barriers that are posed by various membranes (such as skin, cellular membranes or GI tract) deserve a closer look. In addition, coating of nanoparticles to target specific ligands has been demonstrated to improve intracellular accumulation. Therefore issues related with passive vs. active targeting of nanoparticles will bear their own merits and reservations. Saha and colleagues describe the strategies of fabrication for nanoparticulate drug delivery systems, and critical issues related to production of clinically relevant nanoparticles. The authors further discuss the factors that govern in vivo distribution of the nanoparticles. Along similar lines, Torchilin and Sawant describe another interesting platform, ‘phospholipid micelles’ as versatile pharmaceutical nanocarriers. Here, the authors also address an important issue of in vivo stability by using polyethyleneglycol phosphatidylethanolamine (PEG-PE)-based micellar drug delivery systems. It is worth mentioning that the nanoassemblies bearing pegylated molecules (such as liposomes) have proven to be extremely successful for in vivo drug delivery. Two papers are focused on drug delivery aspects resulting from passive accumulation. Sachdeva, Desai and colleagues discuss the nanoparticle interactions with the skin (first barrier). This article also presents the role of cell penetrating peptides (CPP) in modulating trans-dermal drug delivery. Amiji and colleagues present another clinically viable nanoparticulate assembly for drug delivery based on natural oils