STATEMENT OF SIGNIFICANCE: It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers.
MATERIALS AND METHODS: A critical review of preclinical and clinical studies was conducted to summarize the therapeutic interventions that target specific mutations in PDAC, components of the tumor microenvironment, and drug delivery systems, especially nanotechnology, to enhance targeting and efficacy.
RESULTS: Inhibitors and nanotechnology-based targeted therapies have reported promise in preclinical models: drug delivery is enhanced with the loss of PDAC resistance mechanisms. Formulations and combinations targeting KRAS as well as other pathways point toward improved drug delivery over 'orthodox' treatment approaches.
CONCLUSION: This review concludes that although improvement in therapies for PDAC has incrementally been proven in recent literature, however, more research is expected to enhance these approaches so that they can be applied appropriately at the clinical stage. In future studies, it is expected to optimize treatment combinations, address mechanisms of resistance, and improve the delivery of drugs.