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.