Transmucosal macromolecular drug delivery

Prego, Cecilia; García, María L.; Torres, Dolores; Alonso, Marı́a José

doi:10.1016/j.jconrel.2004.07.030

Cited by 306 publications

(153 citation statements)

References 34 publications

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“…NE were prepared under an identical protocol but without the addition of chitosan and HCl in the aqueous phase. To prepare different concentrations of 3OC6HSL-loaded NC, 500 L of an 80 mg/mL ethanolic lecithin solution was mixed with 10 mL of different concentration (10,20,40,60,120,200 and 400 nM) ethanolic 3OC6HSL solutions and 125 µL Miglyol 812 N as the organic phase.…”

Section: Preparation Of the Nanoformulationsmentioning

confidence: 99%

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An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

Qin

Engwer

Desai

et al. 2017

Colloids and Surfaces B: Biointerfaces

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Highlights Chitosan-coated nanocapsules, but not nanoemulsions, influence the -potential of E.coli  A fixed number of nanocapsules binds and promotes aggregation of bacteria  In silico simulations agree closely with experimental results  Chitosan-coated nanocapsules attenuate the bacterial quorum sensing response § These authors contributed equally to this publication * Author for correspondence Colloids and Surfaces B: Biointerfaces 149 (2017) 358-368 AbstractWe examined the interaction between chitosan-based nanocapsules (NC), with average hydrodynamic diameter ~114-155 nm, polydispersity ~0.127, and -potential ~+50 mV, and an E. coli bacterial quorum sensing reporter strain. Dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) allowed full characterization and assessment of the absolute concentration of NC per unit volume in suspension. By centrifugation, DLS, and NTA, we determined experimentally a "stoichiometric" ratio of ~80 NC/bacterium. By SEM it was possible to image the aggregation between NC and bacteria. Moreover, we developed a custom in silico platform to simulate the behavior of particles with diameters of 150 nm and -potential of +50 mV on the bacterial surface. We computed the detailed force interactions between NC-NC and NC-bacteria and found that a maximum number of 145 particles might interact at the bacterial surface. Additionally, we found that the "stoichiometric" ratio of NC and bacteria has a strong influence on the bacterial behavior and influences the quorum sensing response, particularly due to the aggregation driven by NC.

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Section: Preparation Of the Nanoformulationsmentioning

confidence: 99%

“…These systems are formed by spontaneous emulsification [37], as first described by Calvo et al [38]. CS-based NC have become a versatile drug nanocarrier platform, both for lipophilic substances and hydrophilic macromolecules [39][40][41][42][43][44][45].…”

Section: Introductionmentioning

confidence: 99%

An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

Qin

Engwer

Desai

et al. 2017

Colloids and Surfaces B: Biointerfaces

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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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“…Nanoparticle systems possess desirable features for treatment, including: (i) sustained and controlled release of drugs locally (16), (ii) potential to cross the mucosal barrier due to the nanometric size (17)(18)(19), (iii) rapid intracellular trafficking to the perinuclear region of underlying cells (20), and (iv) protection of cargo therapeutics from degradation and removal in the mucus (21,22). However, therapeutic and/or diagnostic particles must overcome the mucosal barrier lining the CV tract to reach underlying cells and avoid clearance.…”

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confidence: 99%

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

Lai¹,

O’Hanlon

Harrold

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

892

1,012

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Nanoparticles larger than the reported mesh-pore size range (10 -200 nm) in mucus have been thought to be much too large to undergo rapid diffusional transport through mucus barriers. However, large nanoparticles are preferred for higher drug encapsulation efficiency and the ability to provide sustained delivery of a wider array of drugs. We used high-speed multiple-particle tracking to quantify transport rates of individual polymeric particles of various sizes and surface chemistries in samples of fresh human cervicovaginal mucus. Both the mucin concentration and viscoelastic properties of these cervicovaginal samples are similar to those in many other human mucus secretions. Unexpectedly, we found that large nanoparticles, 500 and 200 nm in diameter, if coated with polyethylene glycol, diffused through mucus with an effective diffusion coefficient (D eff) only 4-and 6-fold lower than that for the same particles in water (at time scale ‫؍‬ 1 s). In contrast, for smaller but otherwise identical 100-nm coated particles, D eff was 200-fold lower in mucus than in water. For uncoated particles 100 -500 nm in diameter, D eff was 2,400-to 40,000-fold lower in mucus than in water. Much larger fractions of the 100-nm particles were immobilized or otherwise hindered by mucus than the large 200-to 500-nm particles. Thus, in contrast to the prevailing belief, these results demonstrate that large nanoparticles, if properly coated, can rapidly penetrate physiological human mucus, and they offer the prospect that large nanoparticles can be used for mucosal drug delivery. drug delivery ͉ mucosal tissues ͉ particle tracking ͉ PEG

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Transmucosal macromolecular drug delivery

Cited by 306 publications

References 34 publications

An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

An investigation of the interactions between an E. coli bacterial quorum sensing biosensor and chitosan-based nanocapsules

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus

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