# Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies
## 5 Nanocarriers for CF Treatment
Moreover, the treatment of chronic _P. aeruginosa_ infection in CF patients with inhaled amikacin loaded into neutral liposomes composed of DPPC and cholesterol, has improved the antibiotic penetration of the biofilm, suggesting its potential to reach the infected sites in the lungs [201]. Similarly, the encapsulation of tobramycin into negatively charged liposomes composed of DPPC, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol sodium salt (DPPG), has demonstrated higher antibiofilm efficiency on _Burkholderia cepacia_ complex (Bcc) infection in CF patients compared to the free drug [202]. In spite of the advantages of using liposomes as local delivery systems for CF treatment, the nebulization process, which affects the stability of the liposomes, remains a major concern. However, preparing liposomal formulations as DPI, using lyophilization or spray drying technology, has been reported to have a significant improvement on the stability of the liposome [203]. SLN, a lipophilic crystalline matrix, is another non-viral delivery system that could be used in CF therapy. The high physiochemical stability, ease of scaling up, and low cytotoxicity are the key advantages of SLNs [182]. However, the encapsulation capacity is lower than that of liposomes. A recent study has reported the successful delivery of chemically modified CFTR mRNA using SLNs that is (hydrodynamic size of \(104.2\pm 30.5\) nm) composed of dilinoleyball-4-dimethylaminobutyrate (DMA), disteaoylphosphatidylcholine (DSPC), cholesterol, and 1,2-dimyristoyl-rac-glycerol (DMG) [150]. The study findings indicated that the Cl' ion secretion was restored and the CFTR channel was opened [150]. Polymeric nanoparticles function as important drug carriers in CF treatment. Different biocompatible and biodegradable polymers have been widely investigated for use as non-viral delivery systems. Additionally, polymeric nanoparticles have several advantages like high stability and the ability to modify their surfaces by adding certain functional groups or target ligands [204]. Promising results were obtained when PLGA nanoparticles loaded with ciprofloxacin (hydrodynamic size \(190.4\pm 28.6\) nm) and used on different strains of _P. aeruginosa_ to improve the antibacterial activity, reduce the required dose, and enhance the penetration across the mucus layer, thus, enhancing the efficiency of CF antimicrobial therapy [205]. In gene therapy, the injection of polymeric nanoparticles (chitosan-coated PLGA) loaded with chemically modified human CFTR mRNA into the lungs of CFTR-deficient mice, resulted in a significant decrease in Cl' ion secretion and improvement in the critical lung function parameters [206]. Using poloxamine-based copolymer with tetrafunctional structure could be a potential non-viral vector for lung gene therapy. In a recent study, [PERSON] et al. (2019) developed nanoparticles composed of poloxamine 704 and synthetic peptides that self-assembled with nucleic acid molecules. The peptide-poloxamine nanoparticles mediated high transfection of mRNA and pDNA in vitro as well as in the lungs of CF mice without exhibiting cytotoxicity [207]. Additionally, the FDA-approved drug PS-341, a proteasomal pathway inhibitor, loaded in PEGylated PLGA nanoparticles (hydrodynamic size \(121.5\pm 15\) nm) showed controlled and sustained drug release [208]. Dendrimers are synthetic, nanosized, highly branched molecules structurally composed of three main regions--the core, dendritic branches, and functional head groups [209]. The most commonly used dendrimers are the polyamidoamine (PAMAM) dendrimers family [185]. Dendrimers have several advantages over the frequently used nanocarriers. They possess low polydispersity index and can easily perform chemical modifications, thereby allowing better internalization of the loaded drugs across the membrane of the target cells [210]. The beneficial properties of dendrimers have enhanced their use as nanoplatforms for antimicrobial therapy and gene delivery [210].