Translation of combination nanodrugs into nanomedicines: lessons learned and future outlook

Abstract

The concept of nanomedicine is not new. For instance, some nanocrystals and colloidal drug molecules are marketed that improve pharmacokinetic characteristics of single-agent therapeutics. For the past two decades, the number of research publications on single-agent nanoformulations has grown exponentially. However, formulations advancing to pre-clinical and clinical evaluations that lead to therapeutic products has been limited. Chronic diseases such as cancer and HIV/AIDS require drug combinations, not single agents, for durable therapeutic responses. Therefore, development and clinical translation of drug combination nanoformulations could play a significant role in improving human health. Successful translation of promising concepts into pre-clinical and clinical studies requires early considerations of the physical compatibility, pharmacological synergy, as well as pharmaceutical characteristics (e.g. stability, scalability and pharmacokinetics). With this approach and robust manufacturing processes in place, some drug-combination nanoparticles have progressed to non-human primate and human studies. In this article, we discuss the rationale and role of drug-combination nanoparticles, the pre-clinical and clinical research progress made to date and the key challenges for successful clinical translation. Finally, we offer insight to accelerate clinical translation through leveraging robust nanoplatform technologies to enable implementation of personalised and precision medicine.

Nanoemulsions: The rising star of antiviral therapeutics and nanodelivery system—current status and prospects

“…As mentioned above, the NEs systems could be prominently delivering poorly soluble antiviral agents [ 69 , 70 ] as a result of extensive lymphatic absorption. The in vivo murine study revealed 11.5 fold increase in the bioavailability of baicalin (a flavonoid used to treat viral hepatitis) in lymph nodes when delivered with a nanoemulsion carrier [ 71 ].…”

“…Additionally, a single NEs system could accommodate the water-soluble drugs such as the nucleoside and nucleotide analogues of the anti-HIV drug (e.g. tenofovir) and highly water-insoluble drugs (e.g., raltegravir or paclitaxel) and exhibit targeted and long-acting characteristics in vivo [ 70 ].…”

Nanomaterials: Applications in Biomedicine and Biotechnology

“…The issue of removal processes of inorganic nanoparticles from the circulation consequents to discharging their beneficial effects and the lack of biological breakdown/metabolic mechanism, contrasting to most liposomes and polymeric nanoparticles. Hence, there is need for investigation into the effects of chronic use of inorganic nanoparticles on biological activities of the body especially at the cellular and molecular level [60,61]. Inorganic nanoparticles like gold nanoparticles have been used in management of cancer, diabetes, arthritis, and heart and Alzheimer's diseases.…”

Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy

“…More detailed discussions of a working hypothesis can be found in these recent papers [61,137,138]. Reviews by our group describe some important results obtained with lipid nanoparticles for drug delivery to lymph nodes and have further discussion on relevant targeting mechanisms [139][140][141].…”