Permeation enhancing polymers in oral delivery of hydrophilic macromolecules: thiomer/GSH systems

Bernkop‐Schnürch, Andreas; Kast, Constantia E.; Guggi, D.

doi:10.1016/j.jconrel.2003.05.001

Cited by 222 publications

(96 citation statements)

References 40 publications

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“…16 Furthermore, thiomers have been shown to act as permeation enhancers by temporarily opening tight junctions in a reversible manner, which could further enhance the uptake of drugs. 22 The objective of this study was to investigate the possibility of taking chitosan-thioglycolic acid (chitosan-TGA) as a coating material for lipid nanoparticles. Chitosan has been chosen because of its biocompatibility, biodegradability, and safe toxicity profile.…”

Section: Introductionmentioning

confidence: 99%

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Gradauer

Vonach²,

Leitinger³

et al. 2012

IJN

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Aim: To develop mucoadhesive liposomes by anchoring the polymer chitosan-thioglycolic acid (chitosan-TGA) to the liposomal surface to target intestinal mucosal membranes. Methods: Liposomes consisting of phosphatidylcholine (POPC) and a maleimide-functionalized lipid were incubated with chitosan-TGA, leading to the formation of a thioether bond between free SH-groups of the polymer and maleimide groups of the liposome. Uncoated and newly generated thiomer-coated liposomes were characterized according to their size, zeta potential, and morphology using photon correlation spectroscopy and transmission electron microscopy. The release behavior of calcitonin and the fluorophore/quencher-couple ANTS/DPX (8-aminonaphthalene-1,3,6-trisulfonic acid/p-xylene-bis-pyridinium bromide) from coated and uncoated liposomes, was investigated over 24 hours in simulated gastric and intestinal fluids. To test the mucoadhesive properties of thiomer-coated and uncoated liposomes in-vitro, we used freshly excised porcine small intestine. Results: Liposomes showed a concentration-dependent increase in size -from approximately 167 nm for uncoated liposomes to 439 nm for the highest thiomer concentration used in this study. Likewise, their zeta potentials gradually increased from about -38 mV to +20 mV, clearly indicating an effective coupling of chitosan-TGA to the surface of liposomes. As a result of mucoadhesion tests, we found an almost two-fold increase in the mucoadhesion of coupled liposomes relative to uncoupled ones. With fluorescence microscopy, we saw a tight adherence of coated particles to the intestinal mucus. Conclusion: Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system.

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Section: Introductionmentioning

confidence: 99%

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Gradauer

Vonach²,

Leitinger³

et al. 2012

IJN

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“…The use of polymers of high molecular weight with mucoadhesion properties such as chitosan derivatives or thiolated polymers alone or with glutathione demonstrated a powerful capacity to increase UFH and recently Fp oral absorption. [8][9][10] However, potentially, safety concerns have always been considered with these compounds. lipid nanoparticles) have been developed and employed for oral macromolecular drug delivery in general and specifically for UFH or LMWH delivery.…”

Section: Introductionmentioning

confidence: 99%

Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study

Ramadan¹,

Lagarce²,

Tessier-Marteau³

et al. 2011

IJN

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Abstract:Oral anticoagulant therapy could be advanced using lipid-based nanoparticulate systems. This study examined lipid nanocapsules for their oral absorption potential as the first step in developing oral fondaparinux (Fp) novel carriers. Using phase inversion method and cationic surfactants such as hexadecyltrimethyl ammonium bromide (CTAB) or stearylamine (SA), cationic lipid nanocapsules (cLNCs), loaded with Fp on their surface, were prepared and characterized (zeta potential, size and Fp association efficiency and content). In vivo studies were conducted after single oral increasing doses of Fp-loaded cLNCs (0.5 to 5 mg/kg of Fp) in rats and the concentration of Fp in the plasma was measured by anti-factor Xa activity assay. The monodisperse, (∼50 nm), positively charged Fp-cLNCs with high drug loadings demonstrated linear pharmacokinetic profiles of the drug with an increased oral absolute bioavailability (up to ∼21%) compatible with therapeutic anticoagulant effect (.0.2 µg/mL).

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“…patch, film CR), also shown to improve the uptake of hydrophilic macromolecules from the GI tract. [34,35] Thiolated polycarbophils/ glutathione [36] Protection against degrading enzymes and facilitation of transport across intestinal membranes…”

Section: Rhamnolipids[27] P-gp Inhibitionmentioning

confidence: 99%

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules

Dave

Gupta

et al. 2016

Drug Development and Industrial Pharmacy

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The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds. AbstractThe Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability.Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/ hybridization of one or more traditional approaches to improve drug permeability. While some of these approaches have been extremely successful, i.e. drug products utilizing the approach have progressed through the USFDA approval for marketing; others require further investigation to be applicable. This article discusses the commonly studied approaches for improving the permeability of BCS Class III compounds.

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Permeation enhancing polymers in oral delivery of hydrophilic macromolecules: thiomer/GSH systems

Cited by 222 publications

References 40 publications

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties

Oral fondaparinux: use of lipid nanocapsules as nanocarriers and in vivo pharmacokinetic study

Current and evolving approaches for improving the oral permeability of BCS Class III or analogous molecules

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