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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
Falling Liquid Film technique to measure the mucoadhesion of coated and uncoated liposomes.
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f2-ijn-7-2523: Falling Liquid Film technique to measure the mucoadhesion of coated and uncoated liposomes.

Mentions: For the mucoadhesion studies, we used a modified version of the falling liquid film technique previously described by Belgamwar et al.29 A freshly excised porcine small intestine was supplied by Karneta (Graz, Austria); 15 cm pieces were cut from the intestine and washed with physiological saline (37°C). The intestinal tube was cut longitudinally, and a 5 × 9 cm excised sheet was placed on a semicylindrical Plexiglas® support with the mucosal side up (see Figure 2). The intestinal tissue was rinsed with 1 mL of rhodamine-labeled POPC or thiomer-coated liposomes (4:1 molar ratio of SH-groups to maleimide groups) containing a total lipid amount of either 25 or 100 μg/mL. The excess was collected in a petri dish and reapplied. This procedure was repeated ten times and the fluorescence intensity of the final residual solution (It) was measured with a fluorimeter (FluoStar Galaxy; LABTECH, Offenburg, Germany) at an excitation wavelength of 544 nm and an emission wavelength of 590 nm. A 96-well plate (Cellstar®, Greiner Bio-One GmbH, Friedrichshafen, Germany) was used throughout the study. The mean value of at least three measurements was determined to calculate the amount of bound liposomes according to the following equation:


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)

Falling Liquid Film technique to measure the mucoadhesion of coated and uncoated liposomes.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-7-2523: Falling Liquid Film technique to measure the mucoadhesion of coated and uncoated liposomes.
Mentions: For the mucoadhesion studies, we used a modified version of the falling liquid film technique previously described by Belgamwar et al.29 A freshly excised porcine small intestine was supplied by Karneta (Graz, Austria); 15 cm pieces were cut from the intestine and washed with physiological saline (37°C). The intestinal tube was cut longitudinally, and a 5 × 9 cm excised sheet was placed on a semicylindrical Plexiglas® support with the mucosal side up (see Figure 2). The intestinal tissue was rinsed with 1 mL of rhodamine-labeled POPC or thiomer-coated liposomes (4:1 molar ratio of SH-groups to maleimide groups) containing a total lipid amount of either 25 or 100 μg/mL. The excess was collected in a petri dish and reapplied. This procedure was repeated ten times and the fluorescence intensity of the final residual solution (It) was measured with a fluorimeter (FluoStar Galaxy; LABTECH, Offenburg, Germany) at an excitation wavelength of 544 nm and an emission wavelength of 590 nm. A 96-well plate (Cellstar®, Greiner Bio-One GmbH, Friedrichshafen, Germany) was used throughout the study. The mean value of at least three measurements was determined to calculate the amount of bound liposomes according to the following equation:

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