Application of Solid Lipid Nanoparticles to Improve the Efficiency of Anticancer Drugs

Abstract

Drug delivery systems have opened new avenues to improve the therapeutic effects of already-efficient molecules. Particularly, Solid Lipid Nanoparticles (SLNs) have emerged as promising nanocarriers in cancer therapy. SLNs offer remarkable advantages such as low toxicity, high bioavailability of drugs, versatility of incorporation of hydrophilic and lipophilic drugs, and feasibility of large-scale production. Their molecular structure is crucial to obtain high quality SLN preparations and it is determined by the relationship between the composition and preparation method. Additionally, SLNs allow overcoming several physiological barriers that hinder drug delivery to tumors and are also able to escape multidrug resistance mechanisms, characteristic of cancer cells. Focusing on cell delivery, SLNs can improve drug delivery to target cells by different mechanisms, such as passive mechanisms that take advantage of the tumor microenvironment, active mechanisms by surface modification of SLNs, and codelivery mechanisms. SLNs can incorporate many different drugs and have proven to be effective in different types of tumors (i.e., breast, lung, colon, liver, and brain), corroborating their potential. Finally, it has to be taken into account that there are still some challenges to face in the application of SLNs in anticancer treatments but their possibilities seem to be high.

Keywords: cancer; chemotherapy; drug delivery; solid lipid nanoparticles; tumor.

Figure 1

Proposed model of solid lipid nanoparticles structure. Schematic representation of solid lipid nanoparticle (SLN) structure, showing the surfactant, cosurfactant, and the solid lipid matrix.

Figure 2

Schematic representation of the energy landscape of different lipid structures and possible polymorphic transformations. Black arrows represent crystallization process after nanoparticle formation; different structures can be formed in the same process. Red arrows represent spontaneous crystal structure transformation during nanoparticle storage.

Figure 3

Schematic representation of SLNs and different nanostructured lipid carrier (NLC) types depending on their nanostructures. (a) SLN, (b) imperfect NLC, (c) structureless NLC, and (d) multiple oil in solid fat in water O/F/W NLC. Adapted from [18].

Figure 4

MDR mechanisms in cancer cells. Multidrug resistance can be associated to different biochemical processes: (1) active efflux of compounds, (2) loss of surface receptors or alterations in the cell membrane, (3) drug compartmentalization, (4) alteration of drug targets, (5) changes in the cell cycle, (6) elevated drug metabolism, (7) activation of DNA damage repair systems, and (8) inhibition of apoptosis. Adapted from [46].

Figure 5

Enhanced permeability and retention effect in tumor tissues. Under normal conditions (a) extravasation of the nanoparticles does not occur, but in the tumor region (b), the discontinuity of the vascular epithelium and the poor functionality of the lymphatic drainage allow the increase of permeability and retention of SLNs in the microenvironment of the tumor. Adapted from [31].

Figure 6

Drug distribution in solid lipid nanoparticles. Possible ways of incorporation of a drug (pink) in a SLN: (a) homogeneous dispersion in the lipid matrix, (b) incorporation in the shell of the matrix, or (c) distribution in the outer shell.