Nanoparticles for Therapeutic Cargos — Nucleic Acids

Nucleic acids therapy is a revolutionary form of therapy that promises to correct/treat hereditary or acquired diseases by means of foreign genetic material (DNA/RNA as therapeutic entity/drug) introduced into affected cells, tissues or organs. CD Bioparticles can offer a wide range of custom services including nucleic acids delivery nanoparticles formulation, particle analysis and characterization and targeting strategy.

Nucleic Acids Introduction

Nucleic acids have revolutionized biomedical research and have become indispensable research tools. In pharmaceutical development, nucleic acids are at present mostly used as diagnostic tools and for target validation. They have been showing promising results, especially in the treatment of severe diseases (e.g. cancer and AIDS). The physicochemical properties of nucleic acids, with molecular weights ranging from 7 kDa for antisense oligonucleotides to over 1 MDa for plasmid DNA. Nucleic acids comprise DNA and RNA, which are both biological hydrophilic macromolecules, that have negative surface charge and are composed of nucleotides. According to their molecular characteristics, namely hydrophilicity, negative charge, and large size, naked nucleic acids do not enter easily in the cell nucleus. Besides, DNA and RNA molecules have low blood circulation time, must cross the physiological barriers before reaching the cell and are susceptible to extra and intracellular enzymatic degradations.

Basically, treatment of this kind of nucleic acids therapy involves three steps: (i) administration (i.e. introduction of a vector containing nucleic acids into the cell by internalization and avoiding endosomal or lysosomal degradation); (ii) delivery (i.e. transfection of nucleic acids from the local of administration to the nucleus of the target cell); (iii) expression (i.e. production of a therapeutic protein or other nucleic acid product by the cell). Furthermore, for a successful nucleic acids therapy process, an appropriate amount of the therapeutic nucleic acids must be delivered into the target tissue or cell, without exerting significant toxicity.

So far, the most studied nucleic acids delivery systems are liposomes, polymeric and lipid nanoparticles, micelles, and dendrimers. These systems are much safer, can be administered repeatedly without significant immune response, can incorporate plasmids of practically unlimited size and, importantly, can be manufactured under GMP-compliant norms using platforms already existent in the pharmaceutical industry. Their delivery efficiency can be improved through great control towards packing/releasing of the nucleic acid cargo and by adapting the structure of the amphiphile/nucleic acid supramolecular assemblies to the delivery barriers encountered by the plasmid on its way to the target cell.

Lipid nanoparticles show low or non-appearance of toxicity. Advantages of the possibility of achieving controlled drug release and targeting effects, drug protection against degradation, good long-term stability and easy scale up of the manufacturing processes make them potential candidates for nucleic acid delivery. Liposomes can have different surface charges (anionic, cationic or neutral). In addition, phospholipids are natural components of living membrane cells, allowing for a low toxicity potential. Different types of polymers (PEI, PLGA, PLL and so on) have been utilized in delivery systems in a variety of capacities. The main advantage of polymers as delivery systems is their structural flexibility, which affords convenient manipulation of the physicochemical characteristics of the delivery system. Besides, micelles and dendrimers are also considered as good carriers for nucleic acid because of their high manipulability in size, components, structure and surface properties.

Figure 1. Schematic representation of nucleic acids delivery carriers processes towards the inside of cell nucleus. Example for DNA delivery. (C Silva, A., et al. Current drug metabolism, 2015, 16(1), 3-16.)

Our Featured Services

CD Bioparticles is specialized in the development of drug delivery systems and customizing nanoparticles for nucleic acids delivery utilizing our core technologies. With our high-quality products and services, the efficacy of your nucleic acid delivery can be tremendously improved.

We offer well-designed nucleic acids (cDNA/pDNA, iRNA, aptamer and so on) production and its loaded products in lipid nanoparticles, polymeric and, micelles and dendrimers. Carrier properties such as molecular weight, surface charges and charge density, solubility, and hydrophobicity could be designed and engineered at your will; as well as the addition of desired chemical groups or targeting moieties for further functionalization.

1. Jiang, L., Vader, P., Schiffelers, R. M. Extracellular vesicles for nucleic acid delivery: progress and prospects for safe RNA-based gene therapy. Gene therapy, 2017, 24(3), 157.
2. MacLachlan, I. Liposomal formulations for nucleic acid delivery. Antisense drug technology: principles, strategies, and applications, 2007, 2, 237-270.
3. Yang, J., Liu, H., Zhang, X. Design, preparation and application of nucleic acid delivery carriers. Biotechnology advances, 2014, 32(4), 804-817.
4. Juliano, R. L. The delivery of therapeutic oligonucleotides. Nucleic acids research, 2016, 44(14), 6518-6548.

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