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PAMAM-Based Nanocarrier Development

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As pioneers in nanocarrier innovation, CD Formulation harnesses the distinctive properties of polyamidoamine (PAMAM) dendrimers to create cutting-edge systems for nucleic acid delivery. Our comprehensive services encompass formulation, characterization, and testing, ensuring advanced solutions tailored to PAMAM dendrimers.

Applications of PAMAM in Drug Delivery

PAMAM is a dendritic polymer known for its versatile applications in drug delivery. With a highly branched structure, PAMAM offers numerous functional groups that can be easily modified for drug encapsulation and controlled release. Its advantages include high drug-loading capacity, excellent biocompatibility, and the ability to penetrate cellular barriers.

Schematic diagram of the structure and modification of PAMAM dendrimersSchematic diagram of the structure and modification of PAMAM dendrimers (Tarach P.; Janaszewska A., 2021)

How Do We Synthesize PAMAM?

The synthesis of PAMAM dendrimers requires careful control of reactant ratios and reaction conditions to achieve the desired formation and molecular weight.

  • Divergent Method

A stepwise approach is used to build the dendrimers from the core outwards. We first started with the ethylenediamine core and repeated a series of Michael addition reactions and amidations. This allows for good control over generation and surface groups but presents the problem of repeated purification of intermediate products.

  • Convergent Method

In this approach, we first prepare wedge-shaped dendrimers containing functional surface groups and then attach them to the growing dendritic core. It overcomes the difficulty of purifying the intermediate core, but the wedge synthesis and coupling steps may introduce further drawbacks.

  • End Group Functionalization

After the desired generation is achieved, the outermost layer of the PAMAM dendrimers can be functionalized by adding specific end groups or modifying the surface with various molecules, such as targeting ligands or drug molecules.

What Can We Do for PAMAM Modification?

Modification Types Functions
Acetylation
  • Generate acetamide groups to facilitate hydrophobic interactions and cellular uptake.
Amino Acids/Peptides
  • Promote receptor-mediated interactions and cell penetration.
Antibodies
  • Provide high affinity targeting of antigens overexpressed in disease.
PEG
  • Confers stealth properties, modulates hydrophilicity, and prevents aggregation.
Other Polymers
  • Alter surface properties and provide tissue-specific interactions.
Small Molecules
  • Enable the co-delivery of nucleic acids and compounds.

What Nucleic Acid Therapeutics Can We Use PAMAM Dendrimer to Deliver?

  • Small Interfering RNA (siRNA)

We can use PAMAM dendrimers to effectively encapsulate and deliver siRNA molecules to achieve gene silencing and regulation of specific gene expression, helping customers achieve therapeutic purposes.

  • Antisense Oligonucleotides (ASO)

We have found that PAMAM dendrimers show promise in delivering ASOs, and we can help customers develop exclusive PAMAM vectors to target and inhibit the expression of disease-causing genes.

  • DNA

Our expertise lies in developing exclusive PAMAM vectors for the delivery of DNA. Due to the cationic nature of PAMAM, PAMAM dendrimers can complex with DNA to form stable nanocomplexes.

  • Messenger RNA (mRNA)

PAMAM dendrimers have been explored by CD Formulation as carriers for mRNA-based vaccines and therapeutics, allowing efficient delivery of mRNA to cells for protein expression or vaccination purposes.

Advantages of Our PAMAM-Based Nanocarrier Development Services

  • PAMAM is a type of dendrimer with monodispersity and a controllable topology that can deliver bioactive macromolecules to specific areas with high efficiency and minimal side effects.
  • We can easily functionalize nanocarriers by core modification and surface modification of PAMAM to achieve the goal of targeting disease sites.
  • Taking advantage of the fact that the internal tertiary amine in the molecular structure can be protonated under acidic conditions, we optimized the PAMAM nanocarrier to enhance the endosomal escape of genes.
  • The PAMAM nanocarriers we developed have a controllable structure, nanometer size, and defined surface charge.

CD Formulation is a leader in the intelligent design of non-viral gene delivery systems. Leveraging our expertise in macromolecular engineering, we create PAMAM dendrimer-based nanocarriers with tunable properties optimized for diverse nucleic acid therapeutics. If you seek a knowledgeable partner to harness the multifaceted promise of PAMAM for your mRNA, gene editing or antisense medicines, please contact us!

References

  1. Tarach P.; Janaszewska A. Recent advances in preclinical research using PAMAM dendrimers for cancer gene therapy. Int J Mol Sci. 2021, 22(6):2912.
  2. Kheiriabad S.; et al. Dendrimers as a delivery system for small interfering RNA. Methods Mol Biol. 2020, 2115:91-106.
  3. Wong K.H.; et al. Functionalized PAMAM constructed nanosystems for biomacromolecule delivery. Biomater Sci. 2023, 11(5):1589-1606.
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