polyamidoamine

Polyamidoamine (PAMAM) dendrimers are a class of synthetic macromolecules with a highly regular, branched architecture. They comprise a central core, interior amide linkages, and a peripheral shell of primary amine groups, giving a densely packed, monodisperse system. The interior structure contains tertiary amines and amide bonds, while the surface carries multiple primary amines that confer water solubility and a positive charge at physiological pH.

Development and synthesis: PAMAM dendrimers were first described in the 1980s by Tomalia, Newkome, and Baker. They are built generation by generation through iterative divergent or convergent routes, typically starting from an ethylenediamine core and using methyl acrylate and ethylenediamine as building blocks. Generations (G0, G1, G2, …) denote the number of branching layers; higher generations have more surface amines and larger overall size, while remaining highly uniform in size.

Properties: PAMAM dendrimers are highly monodisperse and water-soluble. Generational growth increases molecular weight, radius, and surface amine density. The surface amino groups enable conjugation of drugs, dyes, or targeting ligands and enable electrostatic interactions with nucleic acids or anionic drugs. They can be further modified to tune charge, solubility, and biocompatibility.

Applications: They are explored as carriers for small-molecule drugs, siRNA or DNA, and biologics; as imaging or diagnostic agents; and as catalysts or nanoreactors. Functionalization of the surface supports targeted delivery and reduced nonspecific interactions, while the interior can host guest molecules.

Safety and limitations: The cationic surface of PAMAM dendrimers can cause cytotoxicity and hemolysis, particularly at higher generations. Surface modification (acetylation, PEGylation, or targeting ligands) can reduce toxicity and improve biocompatibility and circulation time. Biodegradability is limited, and clearance and long-term fate depend on generation and surface chemistry; thorough safety assessment is essential for biomedical use.