Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jun-Jul;26(5-6):435-447.
doi: 10.1080/1061186X.2017.1419363. Epub 2018 Jan 10.

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

Qingxin Mu  1 , Jesse Yu  1 , Lisa A McConnachie  1 , John C Kraft  1 , Yu Gao  1   2 , Gaurav K Gulati  1 , Rodney J Y Ho  1   3
Affiliations
Review

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

Qingxin Mu et al. J Drug Target. 2018 Jun-Jul.

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.

Keywords: AIDS; HIV; Nanoparticle; cancer; combination therapy; drug targeting; drug-combination nanoparticle; long-acting; targeted drug delivery.

PubMed Disclaimer

Conflict of interest statement

Disclosure statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1
Figure 1
Literature and clinical trial analysis of NP-based drug delivery studies. (A) Numbers of scientific publications from 1999 to 2016 (data obtained from Web of Science and Pubmed). (B) Numbers of clinical trials from 1999 to 2016 (data obtained from clinicaltrials.gov). (C–E) Types of materials (C), diseases (D) and single/combination NPs (E) in NP drug delivery studies (left: publications; right: clinical trials). Keywords for search in clinical trials: nanoparticles OR liposomes OR lipid nanoparticles OR polymeric nanoparticles OR polymer nanoparticles OR micelles OR nanocrystals OR nano OR nab. For search in Web of Science, the term ‘drug delivery’ was added in combination with above keywords (with ‘AND’ command).
Figure 2
Figure 2
Long acting characteristics of three anti-retroviral agents in a drug-combination (DcNP) nanosuspension. These data represent the time course data of each anti-retroviral agents delivered simultaneously in a drug lipid-nanosuspension. Four macaques each received a subcutaneous injection of the nanoformulated drug and the time course of Lopinavir, Ritonavir and Tenofovir were evaluated in PBMCs and plasma up to 2 weeks by LC-MS/MS. PMBC, peripheral blood mononuclear cell.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Banker GS. Drug products: their role in the treatment of disease, their quality, and their status and future as drug-delivery systems. In: Banker GS, Rhodes CT, editors. Modern pharmaceutics. 4. New York (NY): Marcel Dekker Inc.; 2002. pp. 1–21. revised and expanded.
    1. Kawakami K. Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs. Adv Drug Deliv Rev. 2012;64:480–495. - PubMed
    1. Lipinski CA, Lombardo F, Dominy BW, et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46:3–26. - PubMed
    1. Aungst BJ. Intestinal permeation enhancers. J Pharm Sci. 2000;89:429–442. - PubMed
    1. Singh R, Lillard JW., Jr Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–223. - PMC - PubMed

Publication types

Substances

LinkOut - more resources