Lipid Nanoparticles and Their Hydrogel Composites for Drug Delivery: A Review

Abstract

Several drug delivery systems already exist for the encapsulation and subsequent release of lipophilic drugs that are well described in the scientific literature. Among these, lipid nanoparticles (LNP) have specifically come up for dermal, transdermal, mucosal, intramuscular and ocular drug administration routes in the last twenty years. However, for some of them (especially dermal, transdermal, mucosal), the LNP aqueous dispersions display unsuitable rheological properties. They therefore need to be processed as semi-solid formulations such as LNP-hydrogel composites to turn into versatile drug delivery systems able to provide precise spatial and temporal control of active ingredient release. In the present review, recent developments in the formulation of lipid nanoparticle-hydrogel composites are highlighted, including examples of successful encapsulation and release of lipophilic drugs through the skin, the eyes and by intramuscular injections. In relation to lipid nanoparticles, a specific emphasis has been put on the LNP key properties and how they influence their inclusion in the hydrogel. Polymer matrices include synthetic polymers such as poly(acrylic acid)-based materials, environment responsive (especially thermo-sensitive) polymers, and innovative polysaccharide-based hydrogels. The composite materials constitute smart, tunable drug delivery systems with a wide range of features, suitable for dermal, transdermal, and intramuscular controlled drug release.

Keywords: alginate; cellulose; chitosan; dextran; hydrogels; lipid nanoparticles; nanostructured lipid carriers; polysaccharides; solid lipid nanoparticles.

Figure 1

Combination of hydrogels and lipid nanoparticles.

Figure 2

Structure of lipid nanoparticles according to the physical state of the lipid core, from lipid nano-emulsions (A) to solid lipid nanoparticles (E), through nanostructured lipid carriers (B–D). Different types of nanostructured lipid nanocarriers are possible according to the physical state of the blend of liquid and solid lipids composing the particle core (solid pockets in liquid (B), amorphous blend (C), liquid pockets in solid (D)).

Figure 3

DSC profiles of pure precirol, empty SLN, ibuprofen-loaded SLN (SLN_i) and a mixture of precirol and ibuprofen. Adapted from [23].

Figure 4

Percentage of occurrence of the different types of polymers used to form hydrogels entrapping LNP in the last twenty years.

Figure 5

Cumulative time-release profile of nitrendipine-loaded SLN from different hydrogels. Adapted from [13].

Figure 6

Schematic representation of the irinotecan-loaded SLN-hydrogel system behavior at 25 °C and 36.5 °C. Adapted from [12].

Figure 7

Percentage of the different polysaccharides used in the last 10 years in combination with LNP.

Figure 8

Advantages of combining several components to formulate an innovative drug delivery system that meets ocular administration route expectations. Adapted from [14,34,54].