Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats

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.

Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

“…[22][23][24][25][26][27][28] Furthermore, the liposomes can improve the oral bioavailability of drugs poorly absorbed through the gastrointestinal tract and alter the in vivo distribution of the drugs encapsulated into liposomes, to increase the therapeutic index. 22,[29][30][31][32] Currently, liposomes have been considered one of the most promising drug delivery carriers. Several preparation technologies for liposome development have been studied in recent years, including the film hydration method, ethanol injection method, and high-pressure homogenization.…”

“…[22][23][24][25][26][27][28] Thus, a number of studies showed the liposome carrier could improve the oral bioavailability of poorly bioavailable drugs and change the in vivo distribution of entrapped drugs. [29][30][31][32] For example, Wang et al developed long-circulating nanoliposomes of quercetin, prepared by the emulsified evaporation-low temperature solidification method, using glyceryl behenate and Tween ® 80 as carriers. The researchers showed that the oral absorption of the longcirculating quercetin liposomes in the liposomal formulation, in mice, was better than that of quercetin suspension.…”

Direct Determination of Chitosan–Mucin Interactions Using a Single-Molecule Strategy: Comparison to Alginate–Mucin Interactions

“…General theories of the molecular basis of adhesion have been applied to the discussion of mucoadhesion [31]. Chitosan performs well as a mucoadhesive dosage form both in vivo [32][33][34][35][36][37][38] and in vitro [2,25,26,28,[39][40][41][42][43][44][45][46] and it is therefore of interest to determine the strength of the basic interactions related to this important property.…”

Release behaviour of amoxicillin from chitosan coated liposomes derived from eggs

“…In this study, it was possible to synthesise very small, coated liposomes around 37 nm in size. In some previous studies, thiolated chitosan coated liposomes synthesised for the use in oral peptide delivery were in the size range of 600 -700 nm (Gradauer et al, 2013). In another study where chitosan coated liposomes were used to encapsulate leuprolide, the sizes were…”