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Protamine-Based Nanoparticle Development

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At CD Formulation, we use protamines to engineer versatile nanoparticle platforms. Capitalizing on these cationic proteins' ability to tightly yet reversibly complex with nucleic acids and other polyanionic materials, we have developed precisely engineered multidrug delivery systems. Our nanoparticle formulations allow for efficient encapsulation and controlled release of a wide variety of therapeutic biologics.

What is Protamine?

Self-assembly process of protamine & nucleic acids nanoparticles – CD Formulation

Protamine is a small, strongly alkaline protein found naturally in the sperm cells of many fish and other vertebrates. Protamine's abundant positive charge allows it to interact strongly but reversibly with negatively charged molecules such as DNA and RNA through electrostatic interactions, allowing for tight compression of paternal genetic material during fertilization.

How Do We Develop Protamine Nanoparticles?

Structure of protamine – CD Formulation

  • Protamine Engineering

Our team uses computational design and develops genetic engineering techniques to tune protamine monomers to obtain optimized properties that can vary charge density, thermal stability, and introduce conjugation sites.

  • Protamine Nanoparticles Assembly and Purification

Protamine self-assembles into nanoparticles with nucleic acids or other positively charged molecules under controlled conditions. We continuously optimize assembly parameters such as pH, ionic strength, and purification through dialysis and centrifugation to ensure monodispersity.

  • Protamine Nanoparticle Analysis

Through techniques such as DLS, TEM, SDS-PAGE, we can comprehensively characterize the size, structure, surface charge, and stability of protamine nanoparticles.

  • Protamine Nanoparticle Effectiveness Testing

We can perform cell transfections to evaluate loading efficiency, expression kinetics and safety, and use test results to optimize formulations and protocols.

How Do We Control the Size of Protamine Nanoparticles?

  • Precisely control the salt concentration in the solutions used to dilute protamine and nucleic acid.
  • Iteratively adjust the protamine to nucleic acid ratio.
  • Continuously optimize protamine and nucleic acid concentrations.

Applications of Our Protamine-Based Nanoparticle Development Services

  • Non-Viral Gene Therapy

Our protamine nanoparticles are well-suited to non-viral gene delivery. We can engineer particles optimized for different gene payloads like DNA or mRNA. Tunable properties like surface charge and ligand display facilitate efficient endosomal escape and nuclear localization.

  • Nucleic Acid Vaccine

Our nanoparticles induce strong innate immune responses and antigen presentation needed for vaccination. Functionalized particles can target antigen depots in lymphoid tissues. Entrapment of genetic adjuvants, such as IL-12 or GM-CSF encoding plasmids, further boosts adaptive immunity.

  • RNA Interference

We engineer particles with endosomal escape capabilities for intracellular siRNA/miRNA delivery. Protection against degradation maintains silencing potency in vivo. Ligand targeting enhances uptake by specific cell populations. Controlled kinetic profiling ensures the optimal duration of gene knockdown.

  • Oncolytic Virotherapy

By effectively complexing oncolytic viruses and immune stimulants, our particles induce potent tumor killing via multiple mechanisms. We stabilize viruses during circulation and facilitate their release specifically in the tumor microenvironment. Co-delivery of therapeutic payloads like toll-like receptor agonists or checkpoint inhibitors further boosts antiviral and antitumor immunity.

Why Choose Our Protamine-Based Nanoparticle Development Services?

  • Protamine not only protects nucleic acids from degradation within biological systems but also enhances penetration into cells.
  • According to customer needs, we can precisely control protamine particles with average diameters from 50 nm to 1000 nm.
  • Our protamine-based nanodelivery system is a flexible and versatile platform that can be fused with targeting antibodies for precise delivery, digested into cell-penetrating peptides to increase transfection efficiency, and functional polymers non-covalently blended.

CD Formulation leverages over a decade of expertise in protein engineering and self-assembled nanoparticle platforms to provide comprehensive solutions for engineering versatile protamine-based nanomedicines. Through computational design and multidisciplinary capabilities, we optimize every facet of particle formulation to meet your project-specific goals. Contact us to discuss how we can apply our expertise to advance your nanomedicine program!

References

  1. Jarzebska N.T. et al. Protamine-based strategies for RNA transfection. Pharmaceutics. 2021, 13(6):877.
  2. Ruseska I. et al. Use of protamine in nanopharmaceuticals-A review. Nanomaterials (Basel). 2021, 11(6):1508.
  3. Bäumer N. et al. Targeted siRNA nanocarrier: a platform technology for cancer treatment. Oncogene. 2022, 41(15):2210-2224.
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