PAMAM Dendrimers: A Review of Methodologies Employed in Biopharmaceutical Classification

The oral route is the preferred way of drug administration for most drugs, whose treatment success is directly related to the compound intestinal absorption. This absorption process, in its turn, is influenced by several factors impacting the drug bioavailability, which is extremely dependent on the maximum solubility and permeability. However, optimizing these last two factors, without chemical structural modification, is challenging. Although poly(amidoamine) dendrimers (PAMAM) are an innovative and promising strategy as drug delivery compounds, there are few studies that determine the permeability and solubility of PAMAM-drugs derivatives. Considering this scenario, this paper aimed to carry out a literature review of the last five years concerning biopharmaceutical characterizations of dendrimer delivery systems. In vitro methodologies, such as the Parallel artificial membrane permeability assay (PAMPA) (non-cellular based model) and Caco-2 cells (cellular based model), used for the permeability evaluation in the early stages of drug discovery proved to be the most promising methodologies. As a result, we discussed, for instance, that through the usage of PAMPA it was possible to evaluate the higher capacity for transdermal delivery of DNA of TAT-conjugated PAMAM, when in comparison with unmodified PAMAM dendrimer with a P<0.05. We also presented the importance of choosing the best methods of biopharmaceutical characterization, which will be essential to guarantee the efficacy and safety of the drug candidate.