Laponite-Based Nanocomposite Hydrogels for Drug Delivery Applications

Abstract

Hydrogels are widely used for therapeutic delivery applications due to their biocompatibility, biodegradability, and ability to control release kinetics by tuning swelling and mechanical properties. However, their clinical utility is hampered by unfavorable pharmacokinetic properties, including high initial burst release and difficulty in achieving prolonged release, especially for small molecules (<500 Da). The incorporation of nanomaterials within hydrogels has emerged as viable option as a method to trap therapeutics within the hydrogel and sustain release kinetics. Specifically, two-dimensional nanosilicate particles offer a plethora of beneficial characteristics, including dually charged surfaces, degradability, and enhanced mechanical properties within hydrogels. The nanosilicate-hydrogel composite system offers benefits not obtainable by just one component, highlighting the need for detail characterization of these nanocomposite hydrogels. This review focuses on Laponite, a disc-shaped nanosilicate with diameter of 30 nm and thickness of 1 nm. The benefits of using Laponite within hydrogels are explored, as well as examples of Laponite-hydrogel composites currently being investigated for their ability to prolong the release of small molecules and macromolecules such as proteins. Future work will further characterize the interplay between nanosilicates, hydrogel polymer, and encapsulated therapeutics, and how each of these components affect release kinetics and mechanical properties.

Keywords: Laponite; drug delivery; hydrogel; nanoclay; nanocomposite; nanosilicate.

Figure 1

(A). Structure of Laponite with 2:1 tetrahedral:trioctahedral layering, allowing for intercalation and adsorption of drug molecules. (B). Properties of Laponite particles making them beneficial for use in drug delivery applications.

Figure 2

Structure, physiological stability, and cellular compatibility of Laponite. (A) Laponite (nanosilicates, nSi) are plate-like poly-ions composed of simple or complex salts of silicic acids with a heterogeneous charge distribution and patchy interactions. Transmission electron microscopy (TEM) images show the size of Laponite to be between 20 and 50 nm in diameter. Dynamic light scattering (DLS) shows the hydrodynamic diameter (Dh) of Laponite to be ~32 nm in aqueous conditions, with a polydispersity index (PDI) of ~0.13. The schematic shows the potential interactions of Laponite with cells. Laponite dissociates into individual ions once introduced to a physiological microenvironment (pH < 9). a.u., arbitrary units. (B) The dissolution of Laponite was monitored using inductively coupled plasma mass spectrometry (ICP-MS) at different pH to mimic the extracellular (pH~7.4) and intracellular (pH~5.5) microenvironments. Laponite is expected to be stable at pH~10, and thus, pH 10 was used as control. (C) The effect of Laponite and its ionic dissolution products (silicon, magnesium, and lithium) on cellular viability was evaluated using an MTT assay. Three technical replicates were used for each condition. Half-maximal inhibitory concentration (IC50) is labeled at 50% viability. Concentrations of released ions from Laponite fall well below the IC50 value. (D) Long-term cellular viability after treatment with nanoparticles and its ionic dissolution products was assessed using an alamarBlue assay to detect metabolically active cells (n = 3). Adapted with permission from Ref. [83]. 2022. Science.

Figure 3

Release of free Doxorubicin (DOX) and DOX from Alginate (AG)/Laponite (LP) nanocomposite hydrogels at pH 7.4 (A) and at different pH values in PBS (B). Reprinted with permission from Ref. [119]. 2014, Elsevier.

Figure 4

(A). Visual observation of complexation of nanosilicates (NS; 10 mg/mL) with Lys, BSA, and RNase (2 mg/mL). (B). Diameter of NS only (no protein) and NS–protein complexes measured via dynamic light scattering. NS concentration was 1 mg/mL and protein concentration was 1 mg/mL. * Indicates significant difference (N = 6, p < 0.05). (C). Release profiles of BSA, RNase, and Lys from PEG-only (dashed lines) and NS–PEG (10 mg/mL NS, solid lines) hydrogels. (D). Normalized diffusivity of proteins in PEG-only (No NS) compared to NS–PEG hydrogels. * indicates statistically significant difference (N = 6, p < 0.05). (E). Diameter of NS only (no protein) and NS–protein complexes as a function of pH. NS (100 μg/mL) and protein (50 μg/mL) were incubated for 30 min before measurements. Vertical dashed lines represent isoelectric points of BSA (blue; pI = 4.7), RNase (red; pI = 8.54), and Lys (green; pI = 11.35). Republished with permission from Ref. [39]. 2021. American Chemical Society.