Nanoparticulate systems for respiratory delivery

Regina Scherließ

Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany

Introduction

Nanotechnologies were introduced into drug formulation many years ago and are still one of the hot topics being discussed with respect of their benefits for drug delivery. However, definition of nanoparticles differs. The Royal Society of Chemistry considers nanoparticles as “materials with one or more external dimensions, or an internal structure, of the order of nanometres (1nm = 10-9m) and usually less than 100nm, a view being supported by the ISO definition of “nanoscale” and also the view of the European Commission on nanomaterials [1]. However, broader definitions include all sub-micron particles (particles below 1000 nm). Here, nanoparticle is referred to as sub-micron particle.

Clearly, there are advancements of nanoparticulate formulations e.g. for poorly water soluble drugs in oral delivery (aprepitant, EMEND, MSD) remarkably increasing bioavailability. Other examples for nanoparticulate drug formulations are liposomes for parenteral delivery of cancer therapeutics (Caelix, Schering-Plough Europe) and nanosuspension eye drops (Azopt, Novartis). This already shows that materials to prepare nanoparticles can be various from pure API plus stabiliser in drug nanocrystals to particle forming excipients being used as delivery vehicle and with it bringing additional functionalisation such as PEGylation in the case of liposomes. But what is actually the potential of nanoparticulate systems in respiratory delivery?

Much work has been done on assessing the potential risk of inhaled nanoparticles coming from environmental pollution or smoke. Extensive epidemiological studies have demonstrated an association between air pollution particles and mortality and morbidity of lung and cardiovascular diseases upon acute and especially chronic exposure. Adverse health effects of ambient particulate matter effects are primarily seen in individuals with pre-disposing factors, such as asthma, COPD and atherosclerosis. However, it is very difficult to selectively study these effects as unrealistically high concentrations are needed to provoke an effect in animal studies and cell culture experiments may not be predictive for therapeutic use [2].

Actually, there are already nanoparticulate drug delivery systems for respiratory delivery, thinking about the delivery of ultrafine particles from pMDIs such as in QVAR (Teva) and Foster (Chiesi). However, these are nanoparticles of pure (or almost pure) drug. Drug delivery systems in contrast, typically consist of a particulate carrier or matrix comprising the active pharmaceutical ingredient and adding further functionality such as protection, targeting or controlled release. This talk will focus on particulate drug delivery systems being composed of drug and excipient and intentionally being formulated as nanoparticles.