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Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats
- Source :
- Journal of Controlled Release
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
Abstract
- The aim of the present study was the in vivo evaluation of thiomer-coated liposomes for an oral application of peptides. For this purpose, salmon calcitonin was chosen as a model drug and encapsulated within liposomes. Subsequently, the drug loaded liposomes were coated with either chitosan–thioglycolic acid (CS–TGA) or an S-protected version of the same polymer (CS–TGA–MNA), leading to an increase in the particle size of about 500 nm and an increase in the zeta potential from approximately − 40 mV to a maximum value of about + 44 mV, depending on the polymer. Coated liposomes were demonstrated to effectively penetrate the intestinal mucus layer where they came in close contact with the underlying epithelium. To investigate the permeation enhancing properties of the coated liposomes ex vivo, we monitored the transport of fluoresceinisothiocyanate-labeled salmon calcitonin (FITC-sCT) through rat small intestine. Liposomes coated with CS–TGA–MNA showed the highest effect, leading to a 3.8-fold increase in the uptake of FITC-sCT versus the buffer control. In vivo evaluation of the different formulations was carried out by the oral application of 40 μg of sCT per rat, either encapsulated within uncoated liposomes, CS–TGA-coated liposomes or CS–TGA–MNA-coated liposomes, or given as a solution serving as negative control. The blood calcium level was monitored over a time period of 24 h. The highest reduction in the blood calcium level, to a minimum of 65% of the initial value after 6 h, was achieved for CS–TGA–MNA-coated liposomes. Comparing the areas above curves (AAC) of the blood calcium levels, CS–TGA–MNA-coated liposomes led to an 8.2-fold increase compared to the free sCT solution if applied orally in the same concentration. According to these results, liposomes coated with S-protected thiomers have demonstrated to be highly valuable carriers for enhancing the oral bioavailability of salmon calcitonin.<br />Graphical abstract
- Subjects :
- Calcitonin
Male
Administration, Oral
Pharmaceutical Science
02 engineering and technology
Pharmacology
030226 pharmacology & pharmacy
Article
Salmon calcitonin
Chitosan
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Intestine, Small
Zeta potential
Animals
Sulfhydryl Compounds
Liposome
Chromatography
Thiomer
021001 nanoscience & nanotechnology
Bioavailability
Rats
chemistry
Liposomes
Permeation enhancement
0210 nano-technology
Ex vivo
Subjects
Details
- ISSN :
- 01683659
- Volume :
- 172
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Controlled Release
- Accession number :
- edsair.doi.dedup.....0e3c23b26e885e12574e1ec2b6c9f4bd
- Full Text :
- https://doi.org/10.1016/j.jconrel.2013.10.011