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Design and Optimization Services for Nucleic Acid Drug Delivery System

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Nucleic acid delivery systems are designed and optimized to overcome the limitations of nucleic acid drugs and improve their stability, targeting, and bioavailability in vivo, thus realizing their strong therapeutic potential. CD Formulation possesses the technology and expertise in developing nucleic acid drug delivery systems to offer comprehensive solutions for our clients' products through various approaches.

About the Nucleic Acid Drug Delivery System

Nucleic acid drugs constructed in vitro need to overcome many obstacles to function smoothly in vivo. There are many critical factors affecting the efficiency of nucleic acid delivery, such as the stability of nucleic acids in vivo and their ability to reach the lesion across barriers. Additionally, promoting lysosomal escape, improving protein adsorption of nucleic acid analogs, and enhancing the targeting of nucleic acid analog delivery are crucial for improving delivery efficiency. Understanding the mechanism of action of nucleic acids is essential for designing and optimizing nucleic acid delivery systems. This involves selecting appropriate structural modifications of nucleic acids and drug delivery carriers, along with utilizing advanced technological methods like ultrasound and laser pulses to achieve optimal therapeutic effects.

Fig.1 Engineering nanoparticles for targeted delivery of nucleic acid therapeutics. (Xiao Y, et al., 2019)

Explore Our Design and Optimization Services for Nucleic Acid Drug Delivery System

CD Formulation's nucleic acid drug delivery system design and development will consider the physicochemical properties of your drug molecules, targeting, biostability, drug release rate, application areas, and various other factors to guarantee optimal drug delivery and therapeutic efficacy.

In addition, our nucleic acid delivery technologies enable effective in vitro delivery of nucleic acids encoding gene editing proteins and reprogramming factors. This includes delivery to primary cells, insertion of exogenous DNA sequences into defined genomic sites, and effective in vivo delivery of nucleic acid drugs to the brain, eyes, skin, and lungs.

We currently offer the following types of services for the design and optimization of nucleic acid drug delivery systems.

Controlled-Release Drug Delivery System Design

The design of controlled-release drug delivery systems for nucleic acids primarily involves creating pH-sensitive or enzyme-responsive polymer/liposome carriers to trigger nucleic acid release at the target site, leveraging the characteristics of the tumor microenvironment, such as low pH or high expression of specific enzymes. Additionally, temperature-responsive and biodegradable nucleic acid delivery systems can be designed to achieve controlled release tailored to various customer requirements.

Targeted Drug Delivery System Design

Targeted drug delivery systems for nucleic acids are designed using lipid nanoparticles (LNPs), polymers, nucleic acid nanostructures, and exosomes. Nucleic acid-targeted drugs can also be covalently bound to specific ligands. These ligands range from relatively small molecules (e.g., aptamers, GalNAc, etc.) to large molecules (e.g., peptides, antibodies, etc.). Ligand-directed delivery is expected to enhance targeting to specific cell types.

Modification Services for Drug Delivery System

Modification of nucleic acid delivery systems can be enhanced through surface modifications like polyethylene glycolization, glycosylation, etc., to improve the biocompatibility of the delivery system. These modification services can effectively optimize the performance of nucleic acid delivery systems to meet various application scenarios, offering crucial technical support for nucleic acid drug development.

Our Technologies for Nucleic Acid Drug Delivery System

CD Formulation has professional technical support to meet customer needs for drug system design, including the following.

Technologies	Descriptions
Nucleic Acid Loading Technology	Nucleic acids can be efficiently loaded onto carriers through electrostatic interactions, covalent coupling, etc., to ensure the stability and integrity of nucleic acids in the carriers.
Surface Modification Technology	The technology involves attaching target ligands (e.g., antibodies, peptide sequences, etc.) or stealth molecules like PEG to the carrier's surface. This process enhances the affinity and selectivity towards target cells/tissues, thereby improving drug delivery efficiency.
Targeted Modification Technology	Attach specific targeting ligands, such as antibodies, peptide sequences, sugars, etc., to the carrier surface to enhance the affinity for the target cells/tissues. Utilize passive targeting mechanisms, such as the EPR effect, to achieve selective enrichment of tumor tissues.

Nucleic Acid Drug Delivery System Design and Optimization Process

Firstly, we need to define the key molecular target of the disease to be treated and evaluate the biological function, expression pattern, and pathogenic mechanism of the target. Then, select the appropriate type of nucleic acids, such as mRNAs, siRNAs, ASOs, etc., based on the characteristics of the target.
Subsequently, suitable delivery vectors are selected based on the type of nucleic acid and targeting requirements. These vectors can include liposomes, polymers, viral vectors, and others. The performance of the vector is enhanced through chemical modifications and structural design, focusing on aspects such as stability, targeting, and intracellular transport ability.
Next, an effective process was developed for the preparation of carrier-nucleic acid complexes, and the physicochemical properties of the complexes, such as particle size, were optimized.
Finally, the efficacy of the system in drug delivery is evaluated, continuously validated, and optimized to achieve the best results.

Why Choose Us for Design and Optimization Services of Nucleic Acid Drug Delivery System?

We provide customized services. Considering the physicochemical properties and targeting requirements of nucleic acid drug molecules, we can design and develop drug delivery systems with high targeting and transfection efficiency.
We have established standardized development processes and delivery system development platforms, such as liposomes, polymers, and exosomes. These platforms enable rapid screening and optimization of novel delivery systems.
We offer a wide range of solutions, including full-process services and individual services, to meet the requirements of our customers.
With a stringent quality control system in place, every item, from nucleic acid raw materials to final formulated products, undergoes rigorous testing to ensure it meets the market's quality standards.

Publication Data

Technology: Delivery of nucleic acids utilizing targeted technology

Journal: Journal of the American Chemical Society

IF: 14.4

Published: 2023

Results:

Functional nucleic acid (NA)-based drugs have a wide range of applications because they can alter and control the expression patterns of genes/proteins in cells. In principle, functional nucleic acids need to be precisely and efficiently transported to target cells to ensure their functionality and safety. Since natural NAs are negatively charged, it is difficult to cross the cell membrane, which consists of a lipid bilayer, to enter the target cell. Even worse, delivery of non-targeted functional NAs to non-targeted healthy cells and/or tissues can have unpredictable adverse effects. Therefore, there is a need for precisely targeted delivery of functional NAs to specific cells/organs, especially extrahepatic sites.Since aptamers can bind to various proteins on the cell surface with a high degree of specificity and selectivity, they can act as a molecular recognition unit to accurately bind to the target cells, thus enabling efficient delivery of the cargo. In this perspective, the authors summarize original proof-of-concept strategies based on aptamers for targeted delivery of functional NAs. Several specific examples are then discussed and some future challenges and opportunities are explored from the authors' perspective.

Fig. 2 Schematic illustration of the design of aptamer-based NA targeted delivery systems. (Xie S, et al., 2023)

CD Formulation is committed to providing superior nucleic acid drug delivery system design and optimization services to facilitate the development and understanding of novel therapeutics. Our comprehensive services, accurate results, and dedicated support enable researchers and drug developers to create safer, more effective, and personalized treatments for a wide range of diseases. Contact us today to discuss your project.

References

Xiao Y, Shi K, Qu Y, et al. Engineering nanoparticles for targeted delivery of nucleic acid therapeutics in tumor. MOL THER-METH CLIN D. 2019, 12: 1-18.
Xie S, Sun W, Fu T, et al. Aptamer-based targeted delivery of functional nucleic acids[J]. J. Am. Chem. Soc. 2023, 145(14): 7677-7691.

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