Dendrimer for targeted drug delivery and Vaccine and Immunostimulatory: applications and methods

Abstract Dendrimers are a new class of branched polymeric materials. They all are originated from a single nucleus and described as macromolecules with a three-dimensional branching structure. Dendrimers exist in the blossoming phase of drug delivery in micro and Nanosystems for local or systemic brain administration. Dendrimers are three-dimensional molecules containing structural symmetry. They include continuously branched molecules comprising a central unit called core along with branching points. In dendrimers, branching points are essential for functioning and deciding branching generations. The more the number of branching points, the more is the generation number. Synthesized dendrimers are classified as polyamidoamine (PAMAM) dendrimers, polylysine dendrimers, carbosilane dendrimers, and phosphorus-containing dendrimers. Some researchers classify dendrimers as polyatomic and polyionic dendrimers. However, polyanionic dendrimers are preferred because of their less toxicity. Polyamidoamine class of dendrimers is popular and most widely used as a result of their reproducibility, safety, biocompatibility, stability, small size, and precision. They contain tertiary amine branches and alkyl diamine core and are polyatomic. Dendrimer enters the cells like neurons and astrocytes through receptor-mediated endocytosis and micropinocytosis. The main advantage of dendrimers is their drug-loading ability within the cavities of dendrimers, which acts as the main site of the encapsulation process. They have wide applications in neurodegenerative disorders such as cerebral palsy, AD, PD, prions disease, and also in central nervous system imaging and diagnosis. Cationic phosphorous-containing dendrimers were found to interact with the aggregation of plaques and tangles. It was reported that sialic acid–conjugated dendrimers can inhibit the hyperphosphorylation of tau tangles at a micromolar concentration, which is lower than soluble sialic acid. PPI and G5 polyamidoamine dendrimers show anti-prion activity in neuroblastoma ScN2 cells. It was recently revealed that conjugation of CY5-labeled free activable cell-penetrating peptides to PAMAM dendrimers can differentiate the tumor and adjacent tissues thus increasing tumor resects in a mouse xenograft model. Researchers suggested that the intravenous route of administration effectively penetrates the central nervous system with wide biodistribution for extended therapy. The toxicity of dendrimers markedly depends on factors such as the number of generations, core, and surface properties. Amino-terminated dendrimers were found to be toxic due to the shielding of internal cationic charge by surface modification. To overcome the toxicity of dendrimers, the generation and conjugation with biocompatible groups like Polyethylene glycol is increased. Biologically, dendrimers are highly biocompatible and have predictable biodistribution and cell membrane interacting characteristics determined by their size and surface charge. Dendrimers have optimal characteristics to fill the need for efficient immunostimulating compounds (adjuvants) to increase the efficiency of vaccines. The reason is that dendrimers can provide molecularly defined multivalent scaffolds to produce highly defined conjugates with small-molecule immunostimulators or antigens.