Characteristics and Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers

Abstract
Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have emerged as promising systems for delivering active ingredients. They are derived from physiological, biodegradable, and biocompatible lipids, offering benefits such as sustained release promotion and increased drug stability. These systems are apt for the efficient transport of therapeutic drugs to target tissues while also providing advantages such as facilitating large-scale industrial production, bioavailability, and protection against degradation. The preparation of these nanoparticles involves utilizing diverse types of lipids, surfactants, and solvents. Common lipid varieties encompass triglycerides, steroids, and fatty acids, selected based on the active ingredient for stabilization within the lipid matrix. Preparation methods can be categorized into high-energy and low-energy approaches. This study investigated the differences between the main methodologies used, comparing SLN and NLC systems, and scrutinizing their respective advantages, disadvantages, and applications.
Introduction
Nanotechnology holds significant potential for enhancing the performance and safety of formulations containing bioactive compounds, making it a valuable asset across multiple industrial sectors. Its applications are not limited to therapeutic purposes but can also extend to the food industry, for example, using nanostructures in food packaging, such as silver nanoparticles, which exhibit antimicrobial activity, thus being able to prevent early food spoilage [1,2].
Among the nanostructures already used for active ingredient encapsulation, those based on lipids present some interesting features. Usually, these nanostructures are prepared with biomolecules that can be fully processed by human metabolism, reducing concerns about their biocompatibility [3]. Furthermore, the lipid nanomatrix can delay the degradation of the bioactive molecules and thus increase their stability while also controlling the release of lipophilic substances and protecting the load against enzymatically catalyzed reactions [4,5].
Nanostructures formulated with lipids include liposomes, microemulsions, nanoemulsions, and lipid nanoparticles. The latter combine some benefits of polymeric nanoparticles, liposomes, and microemulsions, with superior biocompatibility, reducing the likelihood of toxicity, and the ability to simultaneously accommodate hydrophilic and lipophilic substances without the use of organic solvents [6,7]. To enhance the performance of the delivered active substances, lipid–drug conjugates (LDCs) can also be encapsulated in these nanostructures. LDCs are drug molecules that have been covalently modified with lipids. The conjugation of lipids to drug molecules increases lipophilicity and also alters other drug properties, providing improved bioavailability, enhanced targeting to the lymphatic system and tumors, and reduced toxicity [8].
Among nanoparticles with a lipid core, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are notable for their capacity to enable the controlled release of the encapsulated active ingredient and its targeted delivery to specific tissues [9,10,11]. These lipid nanostructures consist of a lipid matrix stabilized by surfactants and can be synthesized using various preparation methods involving lipids, solvents, and surfactants. The selection and ratio of surfactants and the lipid matrix significantly affect the encapsulation efficiency of the nanoformulation, as indicated by several studies [12].
Due to their lipophilic properties, lipid nanoparticles can overcome certain physiological barriers, such as the epidermis and the blood–brain barrier, without requiring surface modification [13,14,15]. Moreover, the versatility of commonly used lipid excipients allows for the creation of a wide range of formulations that can modify the drug’s pharmacokinetics, enhancing its characteristics [16,17,18]. When selecting components for the formulation, it is crucial to consider the melting point of the lipid mixture—which should be above body temperature for yielding nanoparticles—loading capacity, drug solubility, and physical structure to ensure they align with the intended application [19,20,21]. Similarly, the type and ratio of surfactants are critical factors in formulation development, as they create an interfacial barrier between the dispersed matrix and the dispersant, preventing nanoparticle aggregation and coalescence [22]. Therefore, this review will discuss the main characteristics and applications of SLNs and NLCs, as well as their primary preparation methods, highlighting their advantages, disadvantages, and limitations. Of the articles studied and selected for this review, 55 are from before 2020.
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Materials
Table 3. Examples of solid lipid nanoparticles (SLNs) and nanostructure lipid carriers (NLCs) prepared by different methods.

Excipients named in the study beside others: Imwitor 900, Brij O10, Polysorbate 80, Phosal 53 MCT, Poloxamer 188, Tween 80, Precirol ATO5, Vitamin E, Lipoid S 100
Queiroz, M.d.C.V.; Muehlmann, L.A. Characteristics and Preparation of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers. J. Nanotheranostics 2024, 5, 188-211. https://doi.org/10.3390/jnt5040012