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Traditional drug delivery systems are inefficient for peptide, protein, and nucleic acid (plasmid DNA, oligonucleotides, or short interfering RNA) delivery; lipid nanocarriers have been exploited as potential delivery and targeting systems for these molecules in recent years. Lipid nanoparticles are developed to address important drawbacks of other lipid-based systems, such as instability and the necessity for surfactants and other toxic substances, to increase loading capacity and resolve manufacturing and scale-up processes problems.
Lipid nanocarriers are the most promising nonviral tools for gene therapy. Their structures are highly attractive for clinical applications due to inexpensive and straightforward manufacturing processes, high stability, and the ability to be administered through different routes, such as the parenteral, pulmonary, oral, and topical routes. A variety of procedures have been reported for preparing lipid nanocarriers. To accommodate the negatively charged nucleic acids, cationic lipid nanocarriers are prepared by including a positively charged cosurfactant in their formulation like benzalkonium chloride, cetylpyridinium chloride, or cetrimide.
Fig.1 The formulation of an oligonucleotide into a self-emulsifying drug delivery system. (Kubackova, 2021)
Regarding the lipid nanocarriers-mediated delivery of nucleic acids, choosing an appropriate combination of cationic and matrix lipids seems vital, as it may significantly affect the transfection efficiency. In the previous study, a nanoparticle formulation consisting of PLGA nanoparticles coated and stabilized with various cationic materials, including CTAB, and protamine is evaluated for delivery of plasmids with significantly high transfection efficiency. A prolonged and high level of gene expression is observed for positively charged coated PLGA nanoparticles. In addition, CTAB has been a widely used reagent during the synthesis of gold nanoparticles for the stability of these nanoparticles and control of their morphologies. Again, these surfactant micelles can be used in drug delivery.
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