Dear experts,
As we dig into scientific papers investigating drug delivery systems using various nano carriers, one thing that attracts attention is the strategies the authors exploited to mask carrier toxicity. One of the well-known approach is to employ molecules with negative charges to mask positive surface charges in an attempt to reduce interaction of the delivery system with negatively charged components such as blood cells and proteins. However, when the surface charge reduced, the first victim will be cellular uptake of the nano carriers. So here comes the dilemma.
In fact, reducing surface charge of the delivery system in order to reduce toxicity is not even an approach! It makes a completely different delivery system with significantly reduced cellular uptake.
Has come the time to change our strategy yet?
At least lead researchers can guide naive ones to orient their studies better.
What do you think?
I think this is too great of a generalization. Cationic charge does not necessarily equate cellular uptake (other components can hinder serum interaction as well), and anionic charges may be advantageous depending on the application. It all depends on what your payload is, what the application/design criteria is, and what the administration route is.
With regard to balance between charge and uptake, there are many systems that employ environment-triggered release that do not suffer greatly on cellular uptake, and there are also ionizable lipids and de-PEGylation strategies that are popular right now for RNA delivery that cleverly uses charge switch in the presence of serum to moderate toxicity but maintain cellular uptake.
Charge reversible particles can be used depending on the application.
I agree with what Dr B.J. Byungji Kim has said. Cellular uptake is quite a diverse phenomenon. Researchers have reported that liposomes having surface charge of -45 mV improved the cellular uptake. So higher negative potential was not a hindrance. Similarly, cationic liposomes may or may not have higher cellular uptake.
In our research, we found that neutral to slightly negative zeta potential was optimal for cellular uptake.
Interesting debate!
I believe charge of a delivery carrier can be a rate limiting step when the uptake is purely driven by charge. However, most of the nanocarriers investigated employ multiple modes of cellular uptake with or without mediation of charge.
It is important to note that charge does play a major role in physical stability characteristics such as particle size and aggregation, process-ability etc. which are equally vital other than mere cellular uptake.
B.J. Byungji Kim Thank you sir for your time and response, useful information.
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