Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs): Fabrication and Functionalization for Impending Therapeutic Applications
Rohini Kanwar, Shivani Uppal, and Surinder Kumar Mehta
Richard Feynman was the man who coined the term ‘nano’ in 1959 in his famous talk ‘There’s Plenty of Room at the Bottom’. Since then, a lot of research has been focused on unleashing the untamed potential of the nanoregime. It proved to be a revolutionary approach which resolved the current glitches in therapeutics (Sanchez and Sobolev, 2010). Nanotechnology diversification into the biomedical domain is quite impressive in comparison to conventional drug delivery systems. Their potential as nanowagons to carry diverse array of drugs and bioactives has been exploited enormously. To date, a number of nanocarriers have been developed e.g. micelles, vesicles, dendrimers, niosomes, liposomes, microspheres, polymersomes, polymeric nanoparticles, carbon nanotubes, silica nanoparticles, and many more (Mishra et al., 2010). Figure 4.1 shows different types of nano delivery carriers explored to date.
However, in 1990 researchers started exploring the field of lipid nanoparticles (LNs), beginning with solid lipid nanoparticles (SLNs) to nanostructured lipid carriers (NLCs). LNs are basically spheres or platelets in the size range of 10-1000nm, and comprise of a physiological lipid core (biodegradable and biocompatible) dispersed in an aqueous emulsifier solution (Pardeike et al., 2009; Montenegro et al., 2016). Various snags like poor aqueous solubility, low intestinal permeability, presystemic metabolism, P-gp efflux, gastro-intestinal degradation, and issues associated with permeability, etc. linked with most of the drugs can be efficiently tackled by the use of LNs and surface functionalized LNs (Chakraborty et al., 2009).
Solid Lipid Nanoparticles (SLNs)
SLNs, termed the first generation of LNs composed of lipids, are in solid form at room and body temperature (instead of liquid
FIGURE 4.1 Structure of different assemblies of colloidal systems for drug delivery.
lipid as present in nano-emulsions) dispersed in aqueous emulsifier solution (Patel et al., 2013). SLNs are fully crystallized and possess an organized crystalline structure where drugs are accommodated within the lipid matrix. SLNs can have a single solid lipid or mixtures of solid lipids such as triglycerides, partial glycerides, fatty acids, steroids, or waxes, being stabilized by surfactant solution (Bunjes, 2011). The solid state of the lipid (similar to polymeric nanoparticles) assists in shielding the accommodated drugs against chemical degradation under harsh conditions by simply decreasing the mobility of drugs in the solid state which thereby leads to a controlled release. SLNs maintain various advantages such as high drug payload, easy scale-up and sterilization, increased physical stability, and excellent tolerance (Weber et al., 2014).
Nanostructured Lipid Carriers (NLCs)
NLCs are termed the second generation of SLNs in which the liquid lipid is added in the inner phase in association with the solid lipid to resolve the snags associated with SLNs. NLCs have achieved better drug solubilization in the presence of liquid lipid, higher drug loading capacity, slow release, and no need for the organic solvents in production, slower polymorphic transition, and a low crystallinity index in the mixture of lipids (Muller et al., 2002). A pictorial representation elucidating the difference between a SLN and NLC particle matrix structure is shown in Figure 4.2.
The present chapter showcases various preparation methods offered by SLNs and NLCs, in detail amplifying their merits and demerits. Surface modification as a panacea to overcome the hiccups of LNs as drug delivery nano wagons is explained and exemplified using hydrophilic modifiers.
Synthesis of Different Types of Lipid Nanoparticles
The synthesis of lipid nanoparticles using a green methodology depends on the energy requirements and the energy constraints of the process involved. Extensive optimizations are required to correlate and balance these two factors. The methods involved can be distinguished on the basis of their unique characteristics and benefits. Depending upon the distinctive energy requirements, percentage yield, ease of applicability, and feasibility, etc., various methods have been exploited to develop SLNs and NLCs (Ramteke et al., 2012).
A top-down approach is applied for the production of both SLNs and NLCs based on encapsulation of the active pharmaceutical ingredients (API) in the melted lipid and dispersing in the amphiphilic surfactant solution. A few different approaches employed for the preparation of SLNs and NLCs, along with their advantages and disadvantages, have been tabulated in Table
4.1 (Ramteke et al., 2012; Ekambaram et al., 2011).