Solid lipid nanoparticles for biologics and drug encapsulation

Paper: Weaver, E.; Sommonte, F.; Hooker, A.; Denora, N.; Uddin, S.; Lamprou, D. A. Microfluidic Encapsulation of Enzymes and Steroids within Solid Lipid Nanoparticles. Drug Deliv. and Transl. Res. 2023. https://doi.org/10.1007/s13346-023-01398-5.

The Lamprou lab, affiliated with Queen’s University Belfast, specializes in three main areas: nanoparticles for imaging and therapy, lab-on-a-chip technology, and therapeutic implants. Their interdisciplinary approach has driven innovation in healthcare since 2012, developing emerging technologies and novel drug delivery devices. The lab is led by Professor Dimitrios Lamprou, a leading expert in pharmaceutical technologies known for his significant contributions to 3D printing, microfluidics, and nanofibers, with over 150 peer-reviewed publications.The Lamprou lab, in collaboration with the Department of Pharmacy‑Pharmaceutical Sciences (University of Bari Aldo Moro) and Immunocore Ltd., used microfluidics to create eco-friendly lipid-based nanocarriers for encapsulating challenging active pharmaceutical ingredients (APIs).

Solid Lipid Nanoparticles have proven their effectiveness in delivering various types of drugs, including chemotherapy drugs, genetic material, and anti-inflammatory medications, through their stability, targeting capabilities, and size.⁴

SLNs present a special structure with a hydrophobic core and a hydrophilic external layer, enabling them to encapsulate both hydrophilic and hydrophobic substances. The solid core, consisting of solid lipids like waxes and glycerides, is responsible for containing the drugs, particularly hydrophobic ones. On the other hand, the surfactant layer on the outside of an SLN enhances stability and targeted drug delivery and can also contain hydrophilic drugs. The choice of drug significantly influences the components used in lipid-based nanocarrier formulation, with cationic lipid cores and surfactants being important for mRNA and DNA delivery.⁵ 

Lipid-based nanoparticles are not limited to SLNs alone, but also include liposomes, niosomes, and exosomes, each with their own distinct properties, as summarized in Table 1.

Figure 1: Structure of an SLN capable of encapsulating an API

Traditional bulk production methods for solid lipid nanoparticles, such as homogenization and microemulsification, have multiple drawbacks including unpredictable particle characteristics, low reproducibility and repeatability, and the environmentally harmful use of solvents.

To address these issues, microfluidics has emerged as a promising approach for lipid-based nanocarrier formulation and encapsulation of drugs.

Microfluidics has gained popularity in drug delivery due to its precise control of flow rates, device design, and mixing angles within submicron channels. These characteristics enable control over particle size, morphology, and encapsulation efficiency, as flow rates have a significant impact on these parameters. The microfluidic approach also improves time efficiency, allowing for continuous production within minutes, unlike traditional batch processes. As a result, microfluidics is particularly well-suited to formulations relying on self-assembly, like liposomes and SLNs, and has been employed for a wide range of APIs, including those used for gene therapy and addressing the COVID-19 pandemic.^6,7,8

Figure 3 : Microfluidics, a promising approach for SLN nanoformulation.[9]

To further explore this area of drug encapsulation, Edward Weaver et al. from the Lamprou Lab aimed to demonstrate microfluidics’ position at the forefront of solid lipid nanoparticle production in general, and for biologic SLNs specifically.

This paper examines the compatibility of trypsin (TRP) and testosterone (TES) for encapsulation in solid lipid nanoparticles using a microfluidic process integrating Fluigent’s Flow EZ. Testosterone was chosen as a positive non-biologic lipophilic API for comparison with previous bulk encapsulation research, while trypsin was evaluated for encapsulating a hydrophilic API in lipid-based nanocarriers. A combination of SLN materials, including tripalmitin (Tri-P), soybean lecithin (LEC), Tween 80 (T80), and cetyl palmitate (CP) in conjunction with Pluronic F68 (P68), was used for nanoformulation using the same experimental setup.

Solid Lipid Nanoparticle Production Method

Fluigent’s Flow EZ was used to synthesize various nanoformulations of solid lipid nanoparticles. The microfluidic device used was a Y-shaped inlet with etched herringbone channels.  The overall system was maintained at a temperature of 60°C to ensure complete dissolution of the materials.

Eight different SLN formulations (F1-F8) were created, with materials dissolved at 60°C to match their final concentration (Table 2). For SLNs encapsulating APIs, TRP and TES were used at varying concentrations, with TRP in the aqueous phase and TES in the organic phase. The optimal flow rate ratio was determined to be 5:1 (aqueous to organic), and samples were collected. The ethanol excess was evaporated through vortex stirring, and SLN formulations were then refrigerated at 5°C for 24 hours.

The API-loaded SLNs were characterized by dynamic light scattering (DLS), zeta potential, atomic force microscopy (AFM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR).