Applications
mRNA encapsulation
mRNA has a wide range of applications in the pharmaceutical and biomedical fields such as protein replacement therapy, gene editing, cellular engineering, and of course, vaccination.
Liposomes and lipid nanoparticles are ideal delivery vectors for mRNA, required to prevent its destruction by the innate immune system and facilitate cellular uptake and release into the cytoplasm.
Not all liposomal delivery systems are created equal. Liposomes must have a specific size, surface functionality, and structure to enable mRNA delivery to target sites. The size of the liposomes will determine their distribution within the body and the ability to cross cell membranes; the surface functionality will determine the targeting efficiency; the structure will dictate the loading efficiency and the ability to release with the cell.
Highly uniform, run-to-run consistent materials are required to generate predictable and consistent pharmacokinetics and generate good patient outcomes. Our novel, continuous flow microfluidics methodologies enable just that.
Controlled release
Controlled release is a well-established area of pharmacology. Active components, pharmaceutical (API) or other, are embedded in a nanocarrier; when this formulation is exposed to physiological conditions, the carrier degrades predictably, releasing the active component over a predetermined period of time. Controlled release enables improved patient quality of life due to reduced number of drug administration cycles and better patient outcomes by substantially increases the circulation time of an active component within the body.
The challenge is to achieve a controlled and predictable release profile consistent for every batch of the formulation fabricated. The release profile is determined by the type of nanocarrier used (Liposome, PLGA, or dendrimer), the material used (polymer's molecular weight, crosslink density, etc.) most importantly, the particle size of the nanocarrier. The size will influence the release rate and the circulation time, and the distribution of the active component within the body.
By generating highly uniform, run-to-run consistent materials, we are able to achieve stable and predictable release profiles across a wide range of active components.
Targeted Delivery
Targeted delivery is a rapidly evolving field with applications spanning diagnostics and clinical treatment. At its core, targeted delivery aims to localize an active component, such as a contrast agent or an API at a malignant site within the body. Targeting is achieved in one of two ways:
Passive targeting relies on the Enhanced Permeability and Retention (EPR) effect, a physiological characteristic of, for example, tumor vessels that leads to the accumulation of nanocapsules
Active targeting relies on particle surface conjugation with targeting species such as antibodies, aptamers, peptides, etc. This gives the particles loaded with active components the ability to recognize and bind to the malignant sites
Precision control over particle size, shape, and structure is essential in both cases. These critical parameters determine blood pool residence time, targeting efficacy, distribution of APIs among particles, and the ability to control the lifetime of the particles within the system.
Conventional manufacturing techniques result in polydisperse materials that vary in their ability to target malignant sites. By contrast, our microfluidics approaches enable the fabrication of highly uniform materials capable of efficient targeting and generating predictable and consistent results.
Bioavailability enhancement
The bioavailability of an active compound is the extent of its absorption at a target site. Depending on the administration route and the nature of the active compound, its bioavailability is determined by its ability to cross membranes, resist pH changes and withstand enzymic degradation.
Crossing cell membranes is most frequently an issue for large molecules, such as those commonly used in oncology and neurological applications. Functionalized nanocarriers offer an effective solution by enabling receptor-mediated endocytosis. Once across the membrane, the nanocarrier will release the active material at a target site.
In the cases where pH sensitivity or enzymic degradation are an issue, nanocarriers can create a physical barrier between the active component and the surroundings. Once the carrier reaches the target site, the shell can be triggered towards release, e.g., by a target pH.
Bioavailability enhancement enables much better patient outcomes by reducing exposure of healthy tissues and maximizing the concentration of an active component at the malignant site. Substantially smaller doses of active compounds can be given at less frequent intervals to achieve the same therapeutic effect.
API solubilisation
Low API solubility is a significant challenge in the development of pharmaceutical formulations. More than 40% of new chemical entities developed today, mainly those developed using advanced combinatorial chemistry and computer-aided drug designing, are hydrophobic, have no practical solubility, and are commonly referred to as "brick dust compounds." Lack of solubility is the most common reason new API do not reach the market or their full potential.
Particle size reduction is a conventional technology that uses milling, spray drying, high-pressure homogenization, etc., to promote solubilization. However, these techniques are limited. They involve high energy input, leading to API's thermal and chemical degradation resulting in non-uniform sized particles prone to precipitation over time.
Nanocarriers overcome conventional techniques' limitations and enable high-quality water-soluble powders with long shelf lives and consistent and predictable behavior in solution.
Protein stabilisation
Biologics and other protein-based API show great potential for the treatment of serious and chronic diseases such as cancer, neurology, and metabolic diseases. These molecules do not travel across membranes easily and are high susceptibility to degradation in the body. This makes their delivery via oral, intravenous, or subcutaneous injection and nasal inhalation routes extremely challenging.
Nanoencapsulation enables all of the benefits outlined above in relation to protein-based API. The drug molecules are protected during storage and administration. The bioavailability of the proteins and peptides is substantially improved due to enhanced ability to permeate membranes (receptor-mediated endocytosis). The therapeutic efficacy of the API is substantially improved by controlled release and targeted delivery.