Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

Abstract

Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

Keywords: drug delivery; encapsulation; lipidic nanovesicles; nanocarriers; particle size; toxicity.

Figure 1

Main lipidic nanocarrier systems and a concise definition of each.

Figure 2

Relative sizes of particles and nanocarriers favourable for cellular uptake and ingestion through different endocytotic pathways. Vesicle size is one of the main parameters that determines clearance by the reticuloendothelial system (RES). The rate of uptake by the immune system cells increases by the increase in the size of the lipidic carriers.

Figure 3

(A,B) schematic representation of typical particle size graphs indicating a polydisperse sample (composed of heterogeneous population of particles) (A); and a monodisperse sample (containing homogenous population of particles) (B); (C,D) representation of the particle size distribution of a sample containing a polydisperse population of particles (with a high PDI value) (C); and a sample containing a monodisperse population of particles (with a low PDI value) (D).