Fernandes, Gasper and Pandey, Abhijeet and Mutalik, Sadhana P and Nikam, Ajinkya Nitin and Seetharam, Raviraja N and Mutalik, Srinivas (2021) Supramolecular dendrimers based novel platforms for effective oral delivery of therapeutic moieties. Journal of Drug Delivery Science and Technology, 64. pp. 1-18. ISSN 1773-2247

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Abstract

Dendrimers are globular three-dimensional synthetic macromolecules that are highly branched with a definite molecular weight. The distinct physicochemical properties and advancements in the synthesis of a variety of biodegradable dendritic scaffolds were studied in several biomedical applications, primarily for the delivery of drug and protein to targeted sites. However, in the context of oral delivery, the knowledge of pharmacokinetics of the dendrimer and its interaction with cellular components is obscure, and therefore further studies will uplift/ elevate the effective clinical translation potential of dendrimers. In this review, we showcase the unique tuneable physicochemical properties of dendrimers alongside the advanced synthetic routes and diverse classes of dendritic scaffolds. In particular, the interaction of dendrimer with biological fluids, cellular uptake, toxicity, and degradation mechanisms are also discussed considering oral delivery/application. We focused exclusively on the influence of dendrimer surface groups and their charge, core chemistry, combination with oral permeation enhancers, effect of lipidation as well as dendrimer conjugation with other nanocarriers as an attempt to improve the therapeutic efficacy of drugs via the oral route. Majority of studies utilize Polyamidoamine (PAMAM) dendrimer to improve the oral bioavailability of drugs; however, toxicity limits its application. Therefore, exploring other classes of dendrimers along with the use of self-assembling dendrimers has been discussed in recent advancements and future perspectives for successful clinical translation of dendrimers in oral delivery

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