Lipoplexes and polyplexes as nucleic acids delivery nanosystems: The current state and future considerations

ABSTRACT

Introduction

Designing safe and effective nucleic acid delivery nanosystems presents a challenge that requires a good understanding of various biological barriers, whose impact is frequently neglected during in vitro assessments. Hence, the development of nanosizing non-viral vectors would benefit from a more thorough physicochemical characterization to establish structure–activity relationships and increase the preclinical data relevance.

Areas covered

This review focused on major barriers of lipoplexes and polyplexes by systemic delivery such as blood and immune cells and is aimed to serve as a prescreening tool for the fast and safe development of both non-viral vectors in vivo. An outline of the preclinical assays to be performed under physiological representative conditions, to better account for or even predict the highly dynamic interactions in humans is also given.

Expert opinion

The rational design of non-viral vectors has shown promising intracellular uptake results in vitro. Translating in vitro success into clinics has gone with progress, but it is still a difficult task to achieve, and more closely mimicking biological environment in vitro assays of lipoplexes and polyplexes may provide more correlated results to in vivo experiments. Clinical practice would benefit from safer non-viral vectors, particularly when avoiding patients' immune responses and toxicity, which is of major concern.

KEYWORDS:

• Lipoplexes
• nanosystems
• nucleic acids delivery
• polyplexes
• toxicity

Article highlights

• Despite advances in lipoplexes and polyplexes, clinical trials are still limited due to obstacles with their toxicity and immune detection.

• Protein corona impact on non-viral vectors can change their blood and immune compatibility properties.

• The non-viral vectors LPNs portrayed the benefits of a rational approach and drive the development of other acid nucleic delivery systems.

• Recent studies revealed that in terms of delivery efficiency and toxicity, distinct polymers have drastic differences.

• Recent formulations of lipoplexes and polyplexes still demonstrate an unsystematic approach regarding blood and immune compatibility testing.

• Some formulations present cytokine induction while demonstrating high levels of cell viability.

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 of this manuscript have no relevant financial or other relationships to disclose.

List of abbreviations

ABC – Accelerated blood clearance

AMBP – Alpha-1-microglobulin/bikunin precursor

APC(s) – Antigen-presenting cell(s)

ApoE – Apolipoprotein E

BPEI – Branched polyethyleneimine

CD4+ – Cluster of differentiation 4

CD8+ – Cluster of differentiation 8

DLS – Dynamic light scattering

DODMA – 1,2-dioleyloxy-3-dimethylaminopropane

DOPC – 1,2-dioleoyl-sn-glycero-3-phosphocholine

DOPE – 1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine

DOTAP – 1,2-dioleoyloxy-3-trimethylammonium propane

DOTMA – 1,2-di-O-octadecenyl-3-trimethylammonium propane

DSPC – 1,2-Distearoyl-sn-glycero-3-phosphocholine

DSPE – 1,2-distearoyl-sn-glycero-3-phosphoethanolamine

EPR – Enhanced permeability and retention effect

FBS – Fetal bovine serum

FDA – Food and Drug Administration

FSC – Fluorescence correlation spectroscopy

GMP – Good manufacturing practices

HBPE-SO₃ – Hyperbranched polyester nanoparticles-sulfonic acid functional groups

IFN-γ – Interferon gamma

IgM – Immunoglobulin M

IL-1β – Interleukin 1beta

IL-6 – Interleukin 6

IL-12 – Interleukin 12

kDa – Kilo dalton

LNP(s) – Lipid nanoparticle(s)

mRNA – Messenger ribonucleic acid

NCL – Nanotechnology Characterization Laboratory

NK cells – Natural killer cells

NTA – Nano tracking analysis

PBAE – Poly-β-amino esters

PCB – Polycarboxybetaine

pDNA – Plasmid deoxyribonucleic acid

PEG – Polyethylene glycol

PEI – Polyethylenimine

pKa – Acid dissociation constant

PLGA – Poly lactic-co-glycolic acid

PLL - Poly-L-lysine

RISC – RNA-induced silencing complex

SEM – Scanning electron microscopy

siRNA – Short interference ribonucleic acid

SNALP – Stable nucleic acid lipid particles

SNL(s) – Solid lipid nanoparticle(s)

TEM – Transmission electron microscopy

TNF-α – Tumor necrosis factor alfa

Additional information

Funding

This paper was funded.