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Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties.

Gradauer K, Vonach C, Leitinger G, Kolb D, Fröhlich E, Roblegg E, Bernkop-Schnürch A, Prassl R - Int J Nanomedicine (2012)

Bottom Line: 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.Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria.

ABSTRACT

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.

Show MeSH
Reaction scheme for the covalent coupling of chitosan-TGA to a maleimide-functionalized phospholipid to form a stable thioether bond.Abbreviations: DOPE-MCC, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane-carboxamide]; TGA, thioglycolic acid.
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f1-ijn-7-2523: Reaction scheme for the covalent coupling of chitosan-TGA to a maleimide-functionalized phospholipid to form a stable thioether bond.Abbreviations: DOPE-MCC, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane-carboxamide]; TGA, thioglycolic acid.

Mentions: Coupling was accomplished by the formation of thioether bonds between free SH-groups of chitosan-TGA and functionalized maleimide-groups of the liposome (see Figure 1). Chitosan-TGA was synthesized according to the method described previously.17 Different amounts of polymer, which were dissolved in deionized water to achieve a concentration of 3 mg/mL, were added to liposomal suspensions, which were diluted via PBS to a concentration of 10 mg/mL, to obtain molar ratios of 1:6, 1:4, 1:2, 1:1, 2:1, 4:1, and 6:1 (SH-groups:maleimide groups). The mixtures were incubated overnight under agitation at room temperature. Control liposomes were treated the same way.


Chemical coupling of thiolated chitosan to preformed liposomes improves mucoadhesive properties.

Gradauer K, Vonach C, Leitinger G, Kolb D, Fröhlich E, Roblegg E, Bernkop-Schnürch A, Prassl R - Int J Nanomedicine (2012)

Reaction scheme for the covalent coupling of chitosan-TGA to a maleimide-functionalized phospholipid to form a stable thioether bond.Abbreviations: DOPE-MCC, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane-carboxamide]; TGA, thioglycolic acid.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3367495&req=5

f1-ijn-7-2523: Reaction scheme for the covalent coupling of chitosan-TGA to a maleimide-functionalized phospholipid to form a stable thioether bond.Abbreviations: DOPE-MCC, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidomethyl)cyclohexane-carboxamide]; TGA, thioglycolic acid.
Mentions: Coupling was accomplished by the formation of thioether bonds between free SH-groups of chitosan-TGA and functionalized maleimide-groups of the liposome (see Figure 1). Chitosan-TGA was synthesized according to the method described previously.17 Different amounts of polymer, which were dissolved in deionized water to achieve a concentration of 3 mg/mL, were added to liposomal suspensions, which were diluted via PBS to a concentration of 10 mg/mL, to obtain molar ratios of 1:6, 1:4, 1:2, 1:1, 2:1, 4:1, and 6:1 (SH-groups:maleimide groups). The mixtures were incubated overnight under agitation at room temperature. Control liposomes were treated the same way.

Bottom Line: 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.Taken together, our current results indicate that thiomer-coated liposomes possess a high potential to be used as an oral drug-delivery system.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biophysics and Nanosystems Research, Austrian Academy of Sciences, Graz, Austria.

ABSTRACT

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.

Show MeSH