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Published Online:https://doi.org/10.2217/nnm-2023-0114

Despite the promising features and aggressive research, the success of nanoparticles in clinical trials is minimal. This manuscript discusses the complex biological barriers that impede the journey of nanoparticles to the target site and the approaches used to overcome them. The ‘6R’ framework (right route, right target, right design, right patient, right combination and right technology) is proposed to improve the clinical translation of nanomedicines. Disease-driven approach contrary to the traditional formulation-driven approach is suggested. Data-driven methods can analyze the relationships between various diseases, patient pathophysiology and the physicochemical properties of different nanomedicines, aiding in the precise selection of the most appropriate treatment options. Further research is needed to evaluate and refine these approaches to develop nanomedicines for clinical success.

Plain language summary

Plenty of work is happening in the field of nanomedicine, but only a few nanomedicines have hit the market. This could be due to many reasons. One of the major reasons is their complex biology. It is imperative to understand how the body reacts to nanomedicines. Obstacles imposed by the body and ways to overcome them are highlighted in this work. The principles of successful nanomedicine design are discussed. This includes proper selection of route, target, design, patient, combination and technology. A framework for evaluating the success of nanomedicine is also proposed. Nanomedicines should be designed using a disease-driven approach. This will help make nanomedicine more viable. Further research is required to test the validity of the proposed model.

Papers of special note have been highlighted as: • of interest; •• of considerable interest

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