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

Area of Science:

• Nanomedicine and Drug Delivery
• Biotechnology and Bioengineering

Background:

• Designing safe and effective nucleic acid delivery nanosystems faces challenges due to biological barriers often overlooked in in vitro studies.
• Nanosizing non-viral vectors requires thorough physicochemical characterization to establish structure-activity relationships and enhance preclinical data relevance.

Purpose of the Study:

• To review major barriers (blood, immune cells) for lipoplexes and polyplexes in systemic delivery.
• To provide a prescreening tool for rapid and safe in vivo development of non-viral vectors.
• To outline preclinical assays under physiologically representative conditions for predicting human interactions.

Main Methods:

• Review of systemic delivery barriers for lipoplexes and polyplexes.
• Focus on in vitro assays that better mimic the in vivo biological environment.
• Outline of preclinical assays under physiologically representative conditions.

Main Results:

• In vitro studies show promising intracellular uptake for rationally designed non-viral vectors.
• Translating in vitro success to clinical applications remains challenging.
• More biologically relevant in vitro assays are needed for improved correlation with in vivo experiments.

Conclusions:

• Thorough physicochemical characterization is crucial for non-viral vector development.
• In vitro assays must better mimic in vivo conditions to improve preclinical data relevance.
• Safer non-viral vectors, minimizing immune responses and toxicity, are essential for clinical practice.