Addressing the challenges to increase the efficiency of translating nanomedicine formulations to patients

ABSTRACT

Introduction

Nanotechnology is in a growth phase for drug delivery and medical imaging. Nanomaterials with unique properties present opportunities for encapsulation of therapeutics and imaging agents, along with conjugation to ligands for targeting. Favorable chemistry of nanomaterials can create formulations that address critical challenges for therapeutics, such as insolubility and a low capacity to cross the blood-brain-barrier (BBB) and intestinal wall.

Areas covered

The authors investigate challenges faced during translation of nanomedicines while suggesting reasons as to why some nanoformulations have under-performed in clinical trials. They assess physiological barriers such as the BBB and gut mucus that nanomedicines must overcome to deliver cargos. They also provide an overview with examples of how nanomedicines can be designed to improve localization and site-specific delivery (e.g., encapsulation, bioconjugation, and triggered-release).

Expert opinion

There are examples where nanomedicines have demonstrated improved efficacy of payload in humans; however, most of the advantages conferred were in improved pharmacokinetics and reduced toxicity. Problematic data show susceptibility of nanoformulations against natural protective mechanisms present in the body, including distribution impediment by physiological barriers and activation of the reticuloendothelial system. Further initiatives should address current challenges while expanding the scope of nanomedicine into advanced biomedical imaging and antibiotic delivery.

KEYWORDS:

• Nanomedicine
• drug delivery
• in vitro-in vivo correlation
• DDS
• EPR
• active targeting

Article highlights

• With unique material properties and high reactivity, nanoformulations offer exciting opportunities in drug delivery, especially for application in chemotherapeutics.

• Despite encouraging in vitro results, nanoformulations often fail to produce efficacy in humans due to low drug loading, difficulty in upscaling, low capacity to target diseased tissue with sufficient drug concentration, as well as rapid filtration from the blood by the reticuloendothelial system.

• Surface functionalization of nanoparticles with hydrophilic polymers and copolymers can lengthen plasma elimination half-life (t_1/2), reduce renal filtration of particles, and alleviate phagocytosis by macrophages.

• Active targeting strategies with nanomedicines for cancer chemotherapeutics have generally produced disappointing results to date, with many of the promising formulations failing in clinical trials despite demonstrating potential in preclinical models.

• Understanding surface chemistry, with control over bioconjugation techniques, improved loading, appropriate release profiles in the target tissue, and performance in relevant in vivo disease models hold the key to therapeutic translation of nanomedicines.

This box summarizes key points contained in the article.

Acknowledgments

The figures were created with Biorender.com.

Declaration of interest

D Brayden has, in the past seven years, consulted for Merck & Co, Takeda, MedImmune, Sanofi, AstraZeneca, Stealth Biotherapeutics, Cheers Health and BiOralix. Furthermore, research in D Brayden’s lab has been funded or co-funded by Nuritas Ltd, Jazz Pharma, Sanofi and Gattefosse. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

S Bhattacharjee would like to thank UCD Research for funding. D Brayden is funded by the Science Foundation Ireland (SFI) CÚRAM Centre for Medical Devices, grant number 13/RC/2073.