Drug delivery to macrophages: a review of nano-therapeutics targeted approach for inflammatory disorders and cancer

ABSTRACT

Introduction

Macrophages are involved in the normal defense of the body; however, the varying phenotypes of macrophages and imbalance in their ratio lead to the impairment of immune response initiating the production of inflammation. As the role of macrophages in immunological disorders and their surface receptors modulation has already been manifested; hence, macrophages can be exploited to make them a viable candidate for targeted delivery, which was not possible with previously designed conventional therapies for the immune disorders.

Areas covered

Nanotechnology is a promising, clear cut, efficient, and adequate approach for targeting macrophages. Literature addresses the receptors available for targeting and the novel small dimensional therapeutic delivery vehicles to target them along with a brief overview of the role of macrophages in these diseases. Furthermore, the patents based on this idea are also listed.

Expert opinion

Targeted drug delivery to macrophages should take into consideration the plasticity of macrophages and their modulation over time in the diseases. A cost-effective scale-up method of development will further facilitate the clinical trials. Besides, the implementation of safety guidelines to target macrophages and the studies of long-term effects of targeted approaches in humans would highly encourage the clinical outcomes.

KEYWORDS:

• Cytokines
• innate immunity
• leishmaniasis
• macrophages
• nanotechnology
• receptor targeting
• TAMs

Article highlights

• Macrophages play a vital role in defending the body against tissue injury and foreign pathogens by regulating the immune response. Macrophages have multiple sub-population with alteration in functions. However, when the coordination between different types is disrupted, macrophages then become the key element for the inflamed conditions and auto-immune disorders.

• The concept of targeted drug delivery to macrophages has emerged after exhaustive research on the surface chemistry of macrophages as well as the recent advancement in nanotechnology. Different polymeric-based nanoparticles, dendrimers, functionalized nano cargoes, and lipid-based nano-drug delivery carriers are becoming popular in the targeted drug delivery because of the small dimension as compared to previously popular conventional drug delivery systems.

• Overall, the targeted drug delivery increases the on-site drug release and enhanced the reduction of parasitic, bacterial, and viral load in the macrophages. Recently, the nano-based targeted drug delivery formulations have been enrolled in pre-clinical and clinical trials, which holds a promising future.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Notes

1. poly(n-butyl cyanoacrylate).

2. hydroxymethylnitrofurazone.

3. Gallium-68 labeled anti-mannose receptor nanobody.

4. PEG-hydrazone-C18.

5. 1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid.

6. methoxypoly(ethylene glycol)-b-poly(histamine methacrylamide).

Additional information

Funding

This work was supported by the GINOP-2.3.2-15-2016-00036 (‘Development and application of multimodal optical nanoscopy methods in life and materials sciences’), Ministry of Human Capacities, Hungary grant 20391-3/2018/FEKUSTRAT.