Solid Lipid Nanoparticles and Nanostructured Lipid Carriers for Drug Delivery Applications
Gabriel Silva Borges1, Mariana Silva Oliveira1, Délia Chaves Moreira dos Santos1, Lucas Antônio Miranda Ferreira1, Guilherme Carneiro2, * 1 Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
2 Department of Pharmacy, Faculty of Biological and Health Sciences, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, MG, Brazil
Abstract
Lipid nanoparticles, such as solid lipid nanoparticles and nanostructured lipid carriers, are drug delivery systems in which solid lipids are dispersed in an aqueous phase stabilized by a surfactant layer. The great interest in these nanocarriers in the latest years is due to the biocompatible lipid matrix, associated with the potential for sustained drug release, and easy transposition to the industrial scale. Moreover, these lipid systems present the ability to prevent drug degradation, and to enhance cell uptake, usually increasing drug efficacy. This chapter will provide an overview of the recent literature on solid lipid nanoparticles and nanostructured lipid carriers for drug delivery applications. Thus, some background information on the origins, composition, characterization parameters and biological applications of these nanocarrier systems will be presented.
Keywords: Nanocarriers, Nanoparticles, Nanostructured lipid carriers, Solid lipid nanoparticles.
* Corresponding author Guilherme Carneiro: Department of Pharmacy, Faculty of Biological and Health Sciences, Federal University of Jequitinhonha and Mucuri Valleys, Diamantina, MG, Brazil;
E-mail: [email protected] INTRODUCTION
Nanotechnology is an exciting research field that, year after year, attracts more attention from researchers all over the world. It is defined as the research area that investigates nanometric systems, which are within the 1-1000 nm size range [1, 2].
In nanomedicine, nanoparticles are usually used for imaging, diagnosis and drug delivery purposes. Nanoparticles used for drug delivery are usually called nanocarriers. Nanocarriers can enhance the pharmacological activity, decrease
toxicity, and allow in vivo administration of drugs. There are many types of materials that can be used to produce nanoparticles for drug delivery, which include polymers, inorganic materials, and lipids [3]. In this context, this review focuses on novel lipid nanocarriers that have attracted much interest over the past 25 years: solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC).
Both SLN and NLC are new generations of nanoemulsions (NE), being SLN the first generation (emerged in the 1990s) and NLC the second generation (emerged in the 2000s). Thus, we will discuss in this chapter the origin, key features, characterization and applications of these systems.
Background
Oil-in-water emulsions are conventional pharmaceutical dosage forms that are formed by oil droplets dispersed within an aqueous medium. Stabilization of oil droplets occurs by the use of surfactants that concentrate on the oil/water interface. Oil-in-water emulsions have been historically administrated by topical (e.g, Diprolene®) and oral (e.g, mineral oil emulsion) routes [4].
Since the 1920s, scientists have examined forms of delivering emulsion by the intravenous route. The purpose of intravenous (IV) delivery of emulsions has been to provide energy and nutrients to hospitalized patients who cannot swallow foods normally. Emulsion droplet size can range from some nanometers to few micrometers, but this is not a limiting factor for the peroral and topical administration of emulsions. However, intravenous administration of particles with a size larger than a few micrometers can provoke vessel occlusion [5-7].
After years of research, in 1961, an IV fat emulsion (10% soybean oil stabilized with egg phospholipids) (Intralipid®) was released in Europe. The Intralipid® droplet sizes were around 276 nm. These small droplet sizes allowed Intralipid® to be delivered by the i.v. route. Since then, emulsions with narrow nanometric droplet size distribution (NE) started to be used for i.v. delivery of lipids [5, 8, 9].
In the beginning, NE were produced only to allow the delivery of oily components for hospitalized patients. A few years later, many drug-loaded NE arrived in the market (e.g, Dizemuls®, Diprivan®, Etomidate-Lipuro®, among others) [10-12]. The success of these systems lies in the possibility of delivering hydrophobic compounds intravenously, but with no pain inconvenience [7, 13]. Moreover, NE present advantages such as toxicological safety and facile production on a large scale [14]. Drawbacks of NE systems, however, include low physical stability and low drug retention, leading to fast drug release and low drug stability. These drawbacks are due to the liquid nature of the lipids used in the NE [12, 15].
Liposomes represent another example of drug nanocarriers. Proposed in the 1960s by Bangham and co-workers [16], liposomes are, probably, the most well-known nanocarriers [17]. Phospholipid-based vesicles in the aqueous medium, the liposomes, entered the market in 1986 with Capture®, an anti-aging product by Dior® [18]. Later, the first pharmaceutical liposomes were approved: Alveofact® (1989), Ambisome® (1990), Doxil® (1995) and Daunoxome® (1996). These products explored the strategy of incorporating drugs into liposomal vesicles for some purposes, including better administration of poorly water-soluble drugs, enhancement of drug pharmacological effects and/or reduction of their toxicological effects [12, 18]. The major drawbacks related to liposomes are their low drug loading (DL) for hydrophobic drugs, difficulty in scaled-up production, and high production costs [10, 12, 15].
Polymers are another type of material widely used for nanocarriers production. The major drawbacks of polymeric nanocarriers include cytotoxicity, high cost of biodegradable polymers and scaled-up production difficulties [10, 12, ...
