Lipid Nanoparticle-based mRNA Delivery System for Biologics

With the development of nanotechnology, lipid nanoparticles have been further developed by functionalizing with targeting ligands or polymers. Lipid nanoparticles have played an important role in mRNA delivery. CD Formulation has been committed to researching and designing lipid nanoparticle-based mRNA delivery systems for years, catering to clients' diverse customization needs for these systems in biologics.

Advantages of Lipid Nanoparticle-based mRNA Delivery

Lipid nanoparticles (LNPs) are composed of ionizable lipids, PEG, cholesterol, and helper lipids, which encapsulate mRNA within an aqueous core to protect it from degradation. The key advantages of LNP-based mRNA delivery include:

• Enhanced Delivery Efficiency: LNPs significantly improve mRNA delivery efficacy.
• Organ- and Cell-specific Delivery: LNPs can be tailored for precise targeting, such as delivering mRNA to the brain via neurotransmitter-derived LNPs.
• Synergistic Therapeutic Effects: LNPs can enhance the therapeutic effects of mRNA-encoded proteins.
• Stability at Room Temperature: LNPs extend the shelf-life of mRNA, reducing cold chain dependency for vaccines.
• Reduced Dosing: Stable LNPs allow lower mRNA doses to achieve therapeutic efficacy.
• Adjuvant Properties: LNPs act as adjuvants, boosting the immune response in vaccines.

Fig.1 Illustration of lipid nanoparticle and its compositions. (Han Na Jung, et al. 2022)

Applications of Lipid Nanoparticle-based mRNA Delivery Systems

LNP-mRNA formulations have broad applications across infectious diseases, cancer immunotherapy, and genetic disease treatments:

• Infectious Diseases: LNP-mRNA formulations offer a robust alternative to traditional vaccines, as demonstrated by their use in COVID-19 vaccines.
• Cancer: LNP-based mRNA delivery has shown promise in cancer immunotherapy, including mRNA vaccines, chimeric antigen receptor (CAR)-engineered immune cells, and cytokine therapies.
• Genetic Diseases: mRNA-based protein replacement therapies are advancing treatments for metabolic disorders like cystic fibrosis, ornithine transcarbamylase deficiency, and methylmalonic acidemia.

Fig.2 LNP-mRNA formulations as COVID-19 vaccines. (Xucheng Hou, et al. 2021)

Our Methods for LNP-based mRNA Delivery System Production

With the help of our innovative lipid nanoparticle technology platform, CD Formulation offers multiple production methods for LNP-mRNA formulations to optimize encapsulation and stability.

Thin-film Hydration

Thin film hydration is the most commonly used technique for lipid nanoparticle production, and this method is a passive encapsulation method. Cationic liposomes are the most used delivery vehicles for mRNA preparations. Lipids are dissolved in an organic solvent and subsequently evaporated by a rotary evaporator to form a thin lipid layer. We use an aqueous buffer solution loaded with mRNA to hydrate the thin layer, and the hydrophobic and hydrophilic parts of the lipid nanoparticles will self-assemble to form multilamellar vesicles.

Ethanol Injection

Ethanol injection is a commonly used technique to form unilamellar liposomes. In this method, we dissolve lipids in ethanol and quickly inject them under stirring into an aqueous buffer containing the drug or compound to be encapsulated, in which the volume is relatively higher than the lipid solution, where vesicles are rapidly formed.

T-junction Mixing

T-junction mixing can produce reproducible and controllable mRNA-loaded LNPs, which encapsulate mRNA with higher encapsulation efficiency. In this method, we generate turbulence by injecting two different solvents at each inlet for rapid mixing at collision.

Microfluidic Mixing

mRNA-LNP was formulated using novel synthetic ionizable lipids. We dissolved Lipids, DSPC, cholesterol, and PEG2k-DMG in ethanol mixed with mRNA buffer solution and dissolved at different total flow rates (TFR) through a microfluidic system. Then we regulated the size of mRNA-LNPs by TFR control, and as TFR increased, the particle size decreased, allowing for control of uniform mRNA-LNP particle size and distribution.

Our Lipid Nanoparticle-based mRNA Delivery System Development Process

Lipid nanoparticle-based mRNA delivery can be achieved via endocytosis followed by electrostatic binding and fusion with the cell membrane via the inverted non-bilayer lipid phase. Relying on our state-of-the-art lipid nanoparticle technology platform, and after many years of research on lipid nanoparticle-based mRNA delivery technology, we have summarized a complete set of mRNA-LNP formulation development processes to guide customers in the personalized customization of different mRNA-LNP formulations.

Fig.3 Our Lipid Nanoparticle-based mRNA Delivery System Development Process. (CD Formulation)

Why Choose CD Formulation?

• Depending on our advanced lipid nanoparticle technologies, we have established and optimized multiple nanotechnology platforms for targeted mRNA delivery.
• Our technicians focus on exploring strategies for constructing lipid nanoparticle-based mRNA delivery systems and can also provide customers with customizing lipid nanoparticles for mRNA delivery systems by choosing suitable fabrication methods.
• We have extensive experience in studying and investigating the construction methods and techniques of lipid nanoparticle-based mRNA delivery systems. Additionally, we are capable of providing services for the development of mRNA-LNP formulations.

Custom Lipid Nanoparticle Development Services for mRNA Delivery

Lipid nanoparticles are the most advanced mRNA delivery system in the clinic, widely used for systemic hepatocyte targeting and intramuscular vaccine administration and have now achieved breakthroughs in the release of mRNA therapeutics in various diseases. At our lipid nanoparticle technology and mRNA delivery technology platform, CD Formulation has focused on designing and developing lipid nanoparticles for mRNA delivery systems, catering to customers' different personalized needs and promoting the rapid development of mRNA therapeutics.

Published Data

As your loyal partner in the development and production of nanoformulations, relying on our world-leading lipid nanoparticle-based mRNA technology system, CD Formulation can provide customers with mRNA-LNP formulation development to help customers come true clinical transformation of mRNA therapy. If you are interested in our lipid nanoparticle-based mRNA technology delivery system for biologics and mRNA-LNP formulation development services, please kindly do not hesitate to reach out to us.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

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STEP 3

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