Chitosan Based MicroRNA Nanocarriers

Vectorization of microRNAs has shown to be a smart approach for their potential delivery to treat many diseases (i.e., cancer, osteopathy, vascular, and infectious diseases). However, there are barriers to genetic in vivo delivery regarding stability, targeting, specificity, and internalization. Polymeric nanoparticles can be very promising candidates to overcome these challenges. One of the most suitable polymers for this purpose is chitosan. Chitosan (CS), a biodegradable biocompatible natural polysaccharide, has always been of interest for drug and gene delivery. Being cationic, chitosan can easily form particles with anionic polymers to encapsulate microRNA or even complex readily forming polyplexes. However, fine tuning of chitosan characteristics is necessary for a successful formulation. In this review, we cover all chitosan miRNA formulations investigated in the last 10 years, to the best of our knowledge, so that we can distinguish their differences in terms of materials, formulation processes, and intended applications. The factors that make some optimized systems superior to their predecessors are also discussed to reach the highest potential of chitosan microRNA nanocarriers.

Conclusions and Prospects

Just recently in 2020, a huge surge of interest in nanomedicine has been noticed with the three phases of: waiting for a vaccine for COVID-19, the discovery of a vaccine based on nanomedicine and gene delivery, and the last phase of controversy gaining public trust with such a new system. This nanomedicine renaissance should be exploited to go further in therapeutic applications that have been overshadowed by the interest in cancer therapeutics. Fields like vaccinology, cardiovascular, hepatic, and renal diseases could use the benefits of nanomedicine. Among these nanomedicine candidates, CS NPs could provide a cheap, sustainable, stable, naturally available, and safer alternative to viral gene delivery. For it to reach the same efficiency of viral vectors, all it needs is a little push using the most recent, standardized, and consistent findings on making an efficient biologically active CS miRNA NP that is stable enough to protect miRNA from the extracellular environment, reach targeted cells, be uptaken and have weak enough binding to release miRNA in the cytoplasm for efficient gene silencing.

Achieving a systematic comparison between different factors (i.e., molar mass, degree of acetylation, N/P ratio, nanoparticle concentration, polyanions addition, and targeting moiety addition) in the same study is needed to reach a valid consensus. Recent Apliterature in the last 10 years showed more consistency and more promising results having more systemic literature-based modifications. Starting with using a molar mass of 10 kDa at least, a DA ≤ 30%, N/P ratio of 1.5–20, and PEGylation/ligand grafting when necessary is a good starting point for any future experiments. Depending on intended applications, the addition of other components to the formulations (as polyanions) can convey beneficial characteristics to the CS miRNA system. That offers a new perspective of CS and an opportunity for a theoretically old/practically new system to be exploited at its best for many therapeutic applications.

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Genedy, H.H.; Delair, T.; Montembault, A. Chitosan Based MicroRNA Nanocarriers. Pharmaceuticals 2022, 15, 1036. https://doi.org/10.3390/ph15091036