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. 2019 Dec 17;7:406. doi: 10.3389/fbioe.2019.00406

Table 2.

Examples of nanotechnological formulations for the CF treatment.

Nanocarrier Composition/material Drug Key finding References
Liposomes and Lipoplexes DPPC/Chol Polymyxin B Increased bioavailability and bactericidal activity against PA Omri et al., 2002
DSPC/DMPG Tobramycin Increase of drug persistence in situ and higher local concentration Omri et al., 1994
DSPC/DMPG Tobramycin Increased drug activity in vivo when encapsulated in fluid liposomal formulation compared with free drug and drug-loaded rigid liposomes Beaulac et al., 1996, 1997
DSPC/DPPC Sachetelli et al., 1999, 2000
DSPC/DPPC
DPPC/DMPG
DPPC/Chol Amikacin Improved penetration within PA biofilm Meers et al., 2008; Okusanya et al., 2009
PC/DOPE/SA Meropenem Higher drug efficacy when encapsulated within cationic liposomes Drulis-Kawa et al., 2006
PC/DOTAP/Chol
DPPC/Chol Amikacin
Gentamicin
Tobramycin
Improved drug efficacy when encapsulated within cationic liposomes Mugabe et al., 2006
DSPC/Chol Amikacin
Tobramycin
Enhanced antibiotic penetration into the bacteria cell membranes Halwani et al., 2007
PC/Chol/DOTAP
PC/DOPE/DOTAP
Gentamicin
Ciprofloxacin
Meropenem
Increased drug activity for lower concentration administered and better drug penetration within bacterial strains Gubernator et al., 2008
DMPC/Chol Gentamicin Better pseudomonal activity compared to free drug Rukholm et al., 2006
DPPC/Chol
POPC/Chol
Polymyxin B Better drug penetration and efficacy within bacterial cells Alipour et al., 2008
EPC/Chol Budesonide Increased drug persistence in the lungs Joshi and Misra, 2001
PC/Chol/DSPG Amikacin Prolonged drug persistence and activity Fielding et al., 1998
PC/Chol/DSPE Gentamicin Increased therapeutic efficacy, increased survival rate of rates Schiffelers et al., 2001
DPPC, DOPC, DPPG Tobramycin Better drug penetration when encapsulated in cationic liposomes, increased drug efficacy Messiaen et al., 2013
DOTMA/DOPE siRNA Efficient restoring of mucus hydration and airway clearance Manunta et al., 2017
DOTMA/DOPE siRNA Effective correction of mucociliary defects Tagalakis et al., 2018
GL76A pGM169 Increase in FEV1 and lung function stabilization Alton et al., 2015
DC-Chol/DOPE CFTR cDNA Partial restoration of Chloride secretion Alton et al., 1993; Middleton et al., 1994
DOTAP pCMV-CFTR Effective gene transfection with no side effects Porteous et al., 1997
DOPC/Chol Colistin Good stability of liposome/drug complex Wallace et al., 2012
Solid Lipid Nanoparticles SA/PC Myriocin Significant reduction of lung inflammation Caretti et al., 2014
Chol/lecithin Tobramycin Better drug deposition within the lungs Pilcer et al., 2006, 2008
DSPC Ciprofloxacin Reduced adverse effects compared to oral and intravenous ciprofloxacin Stass et al., 2013a,b
DMA/DSPC/Chol/DMG cmCFTR Positive CFTR restoration Robinson et al., 2018
GMS Budenoside Good drug dispersion within the Lipid matrix Zhang et al., 2011
Albumin
Gelatin
Chitosan
Ciprofloxacin Sustained and controlled drug release Jain and Banerjee, 2008
Amikacin Higher drug concentration in the lungs with lower side effects Varshosaz et al., 2010, 2013; Ghaffari et al., 2011
Dendrimers PAMAM G4 siRNA Excellent cellular uptake and gene silencing Conti et al., 2014
Bielski et al., 2017
Agnoletti et al., 2017
PAMAM-DENCYS Cysteamine PA infection and growth reduced and rescue of CFTR protein Brockman et al., 2017
Polymeric nanoparticles and microparticles PLGA Curcumin Improved drug bioavailability and efficacy compared to free drug Cartiera et al., 2010
PLGA/PEG PS-341 Sustained and more effective drug release and penetration Vij et al., 2010
PLGA Ciprofloxacin Drug antimicrobial activity and improved mucus penetration Günday Türeli et al., 2017
PEG/PLGA Tobramycin Improved mucus penetration, enhanced antimicrobial activity Ernst et al., 2018
PLGA/chitosan cmRNA Reduced chloride secretion and restoration of lung functions Haque et al., 2018
PVA-Alg/PLGA
Chitosan-Alg/PLGA
Tobramycin Deposition of NPs in the lungs depends on NPs size and composition Ungaro et al., 2012a
PGA/PLGA
Dextran/PLGA
DNase Enhanced mucolytic activity on CF sputum Osman et al., 2013
PLGA Plasmid DNA PLGA-mediated gene transfer can produce prolonged gene expression, despite gene transfer efficiency must be improved Stern et al., 2003
PLGA dec-ODN Inhibition of NF-κB transcriptional activity and reduction of chronic lung inflammation De Stefano et al., 2011, 2013
PEI
Chitosan
miRNA Better efficiency of PEI in facilitating miRNa uptake compared to chitosan McKiernan et al., 2013
PEI Plasmid DNA Improved penetration and transport in CF mucus, reduced activity due to aggregation Ibrahim et al., 2011a
PEG/PEI Plasmid DNA Efficient mucus penetration, improved distribution and retention of NPs, enhanced gene transfer and delivery without significant toxicity Suk et al., 2014
Polixamines mRNA
plasmid DNA
Enhanced mRNA and pDNA expression without exhibiting toxicity Guan et al., 2019

DPPC, dipalmitoyl-phosphatidylcholine; Chol, Cholesterol; DSPC, distearoylphosphatidylcholine; DMPG, dimyristoyl-phosphatidylglycerol; PC, phosphatidylcholine; DOPE, dioleoyl-phosphatidylethanolamine; SA, stearylamine; DOTAP, dioleoyltrimethylammonium propane; DMPC, dimyristoylphosphatidylcholine; EPC, egg phosphatidylcholine; POPC, palmitoyloleoylphosphatidylcholine; DOPC, dioleoylphosphatidylcholine; DPPG, dipalmitoylphosphatidylglycerol; DSPE, istearoyl-sn-glycero-phosphoethanolamine; DSPG, distearoyl-sn-glycerophosphoglycerol; DOTMA, dioleyloxypropyl-trimethylammonium chloride; GL67, Genzyme lipid; PEG, poly(ethlenglycol); PEI, poly(ethylenimine); PLGA, poly(lactic-co-glycolic acid.