Dendrimer
Note 1: For the purpose of determining the nature of constitutional repeating units the free valence is treated as a connection to a CRU.
[18][19][20] Also, it is possible to make dendrimers water-soluble, unlike most polymers, by functionalizing their outer shell with charged species or other hydrophilic groups.
Lower generations can be thought of as flexible molecules with no appreciable inner regions, while medium-sized (G-3 or G-4) do have internal space that is essentially separated from the outer shell of the dendrimer.
Very large (G-7 and greater) dendrimers can be thought of more like solid particles with very dense surfaces due to the structure of their outer shell.
The functional group on the surface of PAMAM dendrimers is ideal for click chemistry, which gives rise to many potential applications.
Ideally, a dendrimer can be synthesized to have different functionality in each of these portions to control properties such as solubility, thermal stability, and attachment of compounds for particular applications.
However, because the actual reactions consist of many steps needed to protect the active site, it is difficult to synthesize dendrimers using either method.
Each step of the reaction must be driven to full completion to prevent mistakes in the dendrimer, which can cause trailing generations (some branches are shorter than the others).
[21] Dendrimers are built from small molecules that end up at the surface of the sphere, and reactions proceed inward building inward and are eventually attached to a core.
This method makes it much easier to remove impurities and shorter branches along the way, so that the final dendrimer is more monodisperse.
Researchers aimed to utilize the hydrophobic environments of the dendritic media to conduct photochemical reactions that generate the products that are synthetically challenged.
Carboxylic acid and phenol-terminated water-soluble dendrimers were synthesized to establish their utility in drug delivery as well as conducting chemical reactions in their interiors.
[34] Dendrimers with hydrophobic core and hydrophilic periphery have shown to exhibit micelle-like behavior and have container properties in solution.
[49][50] This dendrimer scaffold has been designed and shown to have high HPLC purity, stability, aqueous solubility and low inherent toxicity.
The physical characteristics of dendrimers, including their monodispersity, water solubility, encapsulation ability, and large number of functionalizable peripheral groups make these macromolecules appropriate candidates for drug delivery vehicles.
The wide range of terminal functional groups available for dendrimers allows for many different types of linker chemistries, providing yet another tunable component on the system.
[53][54] Polyethylene glycol (PEG) is a common modification for dendrimers to modify their surface charge and circulation time.
For example, folate receptors are overexpressed in tumor cells and are therefore promising targets for localized drug delivery of chemotherapeutics.
Folic acid conjugation to PAMAM dendrimers has been shown to increase targeting and decrease off-target toxicity while maintaining on-target cytotoxicity of chemotherapeutics such as methotrexate, in mouse models of cancer.
[59] Modifying nanoparticle dendrimers with peptides has also been successful for targeted destruction of colorectal (HCT-116) cancer cells in a co-culture scenario.
Conversely, mannose modification of hydroxyl PAMAM-G4 dendrimers was able to change the mechanism of internalization to mannose-receptor (CD206) mediated endocytosis.
Recently, PAMAM dendrimers have been used as delivery vehicles for NSAIDS to increase hydrophilicity, allowing greater drug penetration.
SPL7013, also known as astodrimer sodium, is a hyperbranched polymer used in Starpharma’s VivaGel line of pharmaceuticals that is currently approved to treat bacterial vaginosis and prevent the spread of HIV, HPV, and HSV in Europe, Southeast Asia, Japan, Canada, and Australia.
The company states preliminary in-vitro studies show high efficacy in preventing SARS-CoV-2 infection in cells.
Current research is being performed to find ways to use dendrimers to traffic genes into cells without damaging or deactivating the DNA.
Based on this method, PAMAM dendrimer/DNA complexes were used to encapsulate functional biodegradable polymer films for substrate mediated gene delivery.
Research in this field is vast and ongoing due to the potential for multiple detection and binding sites in dendritic structures.
Dendritic functional polymer polyamidoamine (PAMAM) is used to prepare core shell structure i.e. microcapsules and utilized in formulation of self-healing coatings of conventional[85] and renewable origins.
[90] When a drug is encapsulated within a dendrimer, its physical and physiological properties remains unaltered, including non-specificity and toxicity.
Results from these research has shown that dendrimers have increased aqueous solubility, slowed release rate, and possibly control cytotoxicity of the drugs.
