The potential of chitosan for pulmonary drug delivery

Grenha, Ana; Al‐Qadi, Sonia; Seijo, Begoña; Remuñán‐López, Carmen

doi:10.1016/s1773-2247(10)50004-2

Cited by 58 publications

(44 citation statements)

References 84 publications

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“…The relative proportion of positive charges provided by the protonation of the glucosamine units under slightly acidic conditions and the molecular weight of chitosan play an important role in the development of new applications (Grenha et al, 2010;Tan, 1998). Chitosan exhibits several properties that makes it in an interesting material for pharmaceutical formulations.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, results of transfection efficiency using chitosan-based systems are strongly dependent on chitosan properties (e.g., molecular weight and the relative amount of N-acetylglucosamine units, namely degree of acetylation (DA)) (Lavertu et al, 2006;Santos-Carballal et al, 2015;Strand et al, 2005). Chitosan has been reported as a suitable candidate for transmucosal administration of drugs (Grenha et al, 2010). In addition, it has been observed that after intratracheal administration, the complexes using CS were found in the mid-airways, and transgene expression was observed in epithelial cells (Koping-Hoggard et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Fernández

Santos-Carballal

Weber

et al. 2016

International Journal of Pharmaceutics

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Successful gene therapy requires the development of suitable vehicles for the selective and efficient delivery of genes to specific target cells at the expense of minimal toxicity. In this work, we investigated a non-viral gene delivery system based on chitosan (CS) to specifically address cystic fibrosis (CF). Thus, electrostatic self-assembled CS-pEGFP and CS-pEGFPsiRNA complexes were prepared from high-pure fully characterized CS (Mw ~20 kDa and degree of acetylation ~30%). The average diameter of positively-charged complexes (i.e.  ~ +25 mV) was ~200 nm. The complexes were found relatively stable over 14 h in OptiMEM. Cell viability study did not show any significant cytotoxic effect of the CS-based complexes in a human bronchial cystic fibrosis cell line (s). We evaluated the transfection efficiency of this cell line with both CS-pEGFP and co-transfected with CS-pEGFP-siRNA complexes at (N/P) charge ratio of 12. We reported an increase in the fluorescence intensity of CS-pEGFP and a reduction in the cells co-transfected with CS-pEGFP-siRNA. This study shows proof-of-principle that co-transfection with chitosan might be an effective delivery system in a human CF cell line. It also offers a potential alternative to further develop therapeutic strategies for inherited disease treatments, such as CF.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Fernández

Santos-Carballal

Weber

et al. 2016

International Journal of Pharmaceutics

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“…In recent years, the most frequently explored polysaccharide for the design of nanodelivery systems was chitosan, a cationic polymer composed of repeating β-(1,4)-linked N-acetylglucosamine and D-glucosamine units, which is obtained by chitin deacetylation and assumes different molecular weights and deacetylation degrees (Chiellini et al, 2008;Hassani et al, 2012;Mizrahy and Peer, 2012). Apart from the reported biocompatibility and biodegradability (Dornish et al, 1997;Grenha et al, 2010a;Hirano et al, 1988), the most outstanding properties of chitosan rely on its mucoadhesive character (Lehr et al, 1992) and demonstrated ability to potentiate transmucosal absorption both as molecule (Artursson et al, 1994;Borchard et al, 1996;Portero et al, 2002) and in the form of nanoparticle (Al-Qadi et al, 2012;De Campos et al, 2001;Fernández-Urrusuno et al, 1999a;Prego et al, 2005a;Yamamoto et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Dionísio

Cordeiro

Remuñán‐López

et al. 2013

European Journal of Pharmaceutical Sciences

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Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up.In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.

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“…While silica nanoparticles (14,(37)(38)(39) and dendrimers (32)(33)(34) are effective as antimicrobials, they do not easily break down and thus have limited potential as inhaled therapeutics. Chitosan-based oligosaccharides represent attractive scaffolds for NO delivery, as they are biodegradable and have low toxicity to mammalian cells (40,41). We have previously reported that NO-releasing chitosan oligosaccharides are capable of NO storage/release and of eradicating P. aeruginosa biofilms under aerobic environments at concentrations nontoxic to mammalian cells (15).…”

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confidence: 99%

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Reighard

2015

Antimicrob Agents Chemother

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Chitosan oligosaccharides were modified with N-diazeniumdiolates to yield biocompatible nitric oxide (NO) donor scaffolds. The minimum bactericidal concentrations and MICs of the NO donors against Pseudomonas aeruginosa were compared under aerobic and anaerobic conditions. Differential antibacterial activities were primarily the result of NO scavenging by oxygen under aerobic environments and not changes in bacterial physiology. Bacterial killing was also tested against nonmucoid and mucoid biofilms and compared to that of tobramycin. Smaller NO payloads were required to eradicate P. aeruginosa biofilms under anaerobic versus aerobic conditions. Under oxygen-free environments, the NO treatment was 10-fold more effective at killing biofilms than tobramycin. These results demonstrate the potential utility of NO-releasing chitosan oligosaccharides under both aerobic and anaerobic environments. Pseudomonas aeruginosa is an opportunistic human pathogen that frequently colonizes people with compromised immune systems, such as those with cystic fibrosis (CF) or severe burn wounds (1). The success of P. aeruginosa as a pathogen is related to its multitude of virulence factors, which increase adherence to the host cells, induce inflammation, and disrupt the host immune response (1). Furthermore, P. aeruginosa is intrinsically resistant to many antibiotics due to low membrane permeability and increased expression of ␤-lactamases and efflux pumps (2-4). In addition to this native resistance, P. aeruginosa readily adapts to antibiotic challenge by acquiring resistance genes (3, 5) and forming protective, cooperative communities known as biofilms (6, 7).While all antibiotic resistance mechanisms are not fully understood, at least three main factors reduce antibiotic efficacy against bacterial biofilms compared to planktonic cells. First, P. aeruginosa in biofilms secretes a protective layer of exopolysaccharides that prevent the diffusion of antibiotics (7). In the context of cystic fibrosis, biofilm-bound P. aeruginosa exists predominantly as the mucoid phenotype, characterized by a secreted alginate matrix that provides a physical barrier against the host immune response and antibiotics (8). This exopolysaccharide matrix also prevents the diffusion of oxygen into biofilms, causing P. aeruginosa to switch from aerobic to anaerobic respiration (9). The reduced metabolic activity of P. aeruginosa undergoing anaerobic respiration protects the bacterium against traditional antibiotics that are most effective against rapidly dividing cells, including aminoglycosides and ␤-lactams (10, 11). Finally, biofilms produce persister cells (i.e., dormant bacteria that are highly resistant to chemical disinfectants and exhibit multidrug tolerance) much more frequently than planktonic bacterial cultures (3, 7).The failure of conventional antibiotics to treat P. aeruginosa biofilms and infections necessitates the development of new antibacterial agents. Nitric oxide (NO), an endogenously produced free radical that can disperse (12, 13) and ...

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The potential of chitosan for pulmonary drug delivery

Cited by 58 publications

References 84 publications

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

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