Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2)

Kotzé, A.F; Lueßen, H.L.; Leeuw, Bas J. de; Boer, Bert G de; Verhoef, J.; Junginger, Hans E.

doi:10.1016/s0168-3659(97)00154-5

Cited by 249 publications

(154 citation statements)

References 17 publications

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“…9,11,12 Given a low MW, the polycationic characteristic of CS can be used together with good solubility at a pH value close to physiological ranges. 13 Loading of protein drugs at physiological pH ranges may prevent their bioactivity from decreasing.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

et al. 2006

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Nanoparticles (NPs) composed of chitosan (CS) and poly(γ-glutamic acid) (γ-PGA) were prepared by a simple ionic-gelation method for oral insulin delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and γ-PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the crystal structure of CS was disrupted after it was combined with γ-PGA. The diameters of the prepared NPs were in the range of 110-150 nm with a negative or positive surface charge, depending on the relative concentrations of CS to γ-PGA used. The NPs with a positive surface charge (or shelled with CS) could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. After loading of insulin, the NPs remained spherical and the insulin release profiles were significantly affected by their stability in distinct pH environments. The in vivo results clearly indicated that the insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic rat model.

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Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

et al. 2006

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“…[15][16][17] Thus, the prepared Lac-NCTD-TMC-NPs, with a mean particle size of around 120 nm, can pass through the fenestrated sinusoids and accumulate in the tumor sites of the liver. The small particle size reduced the adverse reaction of Lac-NCTD-TMC-NPs on normal hepatic cells, by reducing the passive targeting in the liver.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism is that CS and TMC can open tight junctions. 17 TMC's high degree of quaternization (65%) enables high absorption-enhancing properties. Moreover, TMC-containing formulations reportedly exceed the potency of CS in mucoadhesion.…”

Section: Dovepressmentioning

confidence: 99%

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers

Guan

Zhu²,

Liu³

et al. 2012

IJN

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Abstract:In this paper, novel liver-targeting nanoparticles (NPs), lactosyl-norcantharidin (Lac-NCTD)-associated N-trimethyl chitosan (TMC) NPs (Lac-NCTD-TMC-NPs), were prepared using ionic cross-linkage. The physical properties, particle size, and encapsulation efficiency of the nanoparticles were then investigated. The continuous line of heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2) cell monolayer model was used to study the transport mechanism of Lac-NCTD, and the effects of factors such as time, temperature, pH level, drug concentration, enhancers, and inhibitors. This model was also used to indicate the differences among Lac-NCTD, Lac-NCTD-associated chitosan NPs (Lac-NCTD-CS-NPs), and Lac-NCTD-TMC-NPs in the absorption and transportation of membranes. Drug concentration levels were measured using high-performance liquid chromatography. Active transport and paracellular transport were suggested to be both the primary and secondary mechanisms for Lac-NCTD absorption, respectively. Lac-NCTD uptake and absorption were not controlled by pH levels, but were positively correlated to uptake time, and negatively correlated to temperature. The basolateral to apical apparent permeability coefficients (Papps) were higher than those of the apical to basolateral values. The inhibitor of P-glycoprotein and the multidrug resistance-associated protein 2 significantly enhanced the uptake amount of Lac-NCTD. Compared with Lac-NCTD, Lac-NCTD-CS-NPs and Lac-NCTD-TMC-NPs significantly enhanced drug absorption. Additionally, the latter exhibited stronger action. Lac-NCTD-NPs could penetrate the plasma membrane of Caco-2 cells and translocate into the cytoplasm and even into the nucleus. Nanoparticles were uptaken into Caco-2 cells through the endocytosis pathway.

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“…The complete quaternization is unnecessary to make the polymer soluble at neutral or alkaline pH, in fact, a quaternization degree (QD) of around 40% is sufficient for this purpose (Snyman et al, 2002;Di Colo et al, 2004a). TMC has proved a potent permeation enhancer of hydrophilic molecules and macromolecules across the intestinal epithelium in neutral environments (Kotzé et al, 1997;Kotzé et al, 1998;Thanou et al, 2000). A study of the enhancing effects of TMC polymers having varying QD on the permeation of the hydrophilic mannitol or PEG 4000 across epithelial cell monolayers (Caco-2) demonstrated the existence of an optimum QD, beyond which the permeability was no further increased .…”

Section: Eye Dropsmentioning

confidence: 99%

“…On the other hand, the tobramycin concentration in the aqueous was below the limit of detection, even with the TMC-containing insert. It is known that TMC is able to enhance the paracellular penetration of hydrophilic molecules or macromolecules across cell monolayers, such as the intestinal epithelium, by opening the tight junctions between cells (Kotzé et al, 1997;Kotzé et al, 1998;Thanou et al, 2000). The results obtained with tobramycin (Zambito et al, 2006a) demonstrate that the tight junctions of such a stratified epithelium as the cornea are not effectively opened by TMC, at least to such an extent as to allow therapeutically effective penetration of hydrophilic drugs of the tobramycin molecular size.…”

Section: In Situ-gelling Systemsmentioning

confidence: 99%

Polysaccharides as Excipients for Ocular Topical Formulations

Zambito¹,

Colo²

2011

Biomaterials Applications for Nanomedicine

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Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2)

Cited by 249 publications

References 17 publications

Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

Uptake and transport of a novel anticancer drug-delivery system: lactosyl-norcantharidin-associated N-trimethyl chitosan nanoparticles across intestinal Caco-2 cell monolayers

Polysaccharides as Excipients for Ocular Topical Formulations

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