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.
Highlights
One of the biggest challenges in pharmaceutical technology nowadays remains the design and the complete characterization of a sustainable and targeted drug delivery system, for poorly water-soluble or insoluble active compounds
Small aliquots of the studied sample are regularly withdrawn, dialyzed or passed through ultrafiltration or solid phase extraction (SPE) to separate the free drug from the encapsulated drug, lipid nanoparticles (LNP) are destroyed with organic solvent and the final sample is injected into High-Performance Liquid Chromatography (HPLC) [19,25]
Differential Scanning Calorimetry (DSC) was used by Strasdat and collaborators to measure the influence of several bead production methods and processes on the structure and quantity of lipids constituting the core of LNP embedded in alginate capsules
Summary
One of the biggest challenges in pharmaceutical technology nowadays remains the design and the complete characterization of a sustainable and targeted drug delivery system, for poorly water-soluble or insoluble active compounds. Lipid nanoparticles (LNP) are colloidal lipophilic systems made of a lipid core stabilized in aqueous media by a single layer of surfactants (phospholipids, poly(ethylene glycol)-based (PEGylated) surfactants, etc.) (Figure 2). The first is entrapment efficiency (Ee), defined as: LNP are used as drug delivery systems, protecting and stabilizing hydrophobic active molecules in aqueous solutions. Their primary advantage is the improvement of the bioavailability of drugs, lipophilic molecules that can be better solubilized in the lipid core than in aqueous environments. The lipophilic core of lipid nanoparticles entraps active ingredients, while the surfactant membrane, generally consisting solely or partially of phospholipids, ensures the stability of LNP in hydrophilic environment. Lipid nanoparticles are known to create a mono-layer film on the skin, limiting water evaporation and improving skin hydration [16]
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