Targeted delivery of nanoparticles for the treatment of lung diseases

Abstract

Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest. This article reviews research performed over the last decades on the application of nanoparticles administered via different routes of administration for treatment or diagnostic purposes. Nanotoxicological aspects of pulmonary delivery are also discussed.

Introduction

Over the last decades, colloidal drug delivery systems and especially nanoparticles have received great attention. Nanoparticles can be administered via different routes of administration such as parenteral, oral, intraocular, transdermal or pulmonary inhalation. Aerosol therapy using particulate drug carrier systems is becoming a popular method to deliver therapeutic or diagnostic compounds either locally or systemically [1] as shown by the development of inhalable insulin [2]. This is due to the large alveolar surface area suitable for drug absorption, the low thickness of the epithelial barrier, extensive vascularization and relatively low proteolytic activity in the alveolar space compared to other routes of administration and the absence of the first-pass metabolism [3], [4], [5], [6]. In general, nanoparticle delivery to the lungs is an attractive concept because it can cause retention of the particles in the lungs accompanied with a prolonged drug release if large porous nanoparticle matrices are used [7]. On the other hand studies have shown that nanoparticles uptake by alveolar macrophages can be reduced if the particles are smaller than 260 nm [7], [8], [9]. Both effects combined might improve local pulmonary drug therapy. However, the particle size of medically used nanoparticles is too small to be suitable for direct lung delivery. A prerequisite for deep lung delivery is the design of proper carrier systems [1]. Successful delivery of inhaled particles depends mostly on particle size and particle density, and hence, the mass median aerodynamic diameter [10]. The respirable fraction of an inhalable powder is generally the fraction of particles with an aerodynamic diameter ranging between 1 and 5 µm. This size range guarantees a maximum deposition in the deep lung [11]. In this article, we review research performed during the last three decades in the area of nanoparticle delivery with special focus on nanoparticle targeting to the lungs. While direct pulmonary delivery of dry powder formulations containing nanoparticles is rather new, this article will also review nanoparticle delivery to the lungs via different routes of administration.