Lectin-conjugated PLGA nanoparticles loaded with thymopentin: Ex vivo bioadhesion and in vivo biodistribution

Yin, Ya-Shu; Chen, Dawei; Qiao, Mingxi; Wei, Xiuyan; Hu, Haiyang

doi:10.1016/j.jconrel.2007.06.024

Cited by 99 publications

(49 citation statements)

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“…5) Recently, it was demonstrated that lectin-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles display increased intestinal bioadhesion and furthermore increase the oral bioavailability of peptide drugs. 6,7) It was the aim of the study to (1) synthesize a novel polymer-lectin conjugate by covalently attaching WGA to carbopol, (2) investigate if the covalent attachment of WGA does decrease or abolish the binding activity of WGA to N-acetyl-D-glucosamine, (3) prepare CP-lectin coated liposomes, and (4) evaluate these coated liposomes concerning intestinal bioadhesion and effect on the oral absorption of incorporated calcitonin.…”

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confidence: 99%

Carbopol-Lectin Conjugate Coated Liposomes for Oral Peptide Delivery

2010

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Although the oral administration route can be regarded as the most convenient one, most therapeutic peptides and proteins are available only as injections. This is due to the low bioavailability of orally administered peptide drugs, which is caused by a number of barriers, including the enzymatic barrier 1) and the permeation barrier.2) As oral peptide delivery is highly demanded by patients, various approaches have been developed in recent years to overcome these barriers and to achieve sufficient bioavailability after oral administration. One promising approach is the coating of liposomes with bioadhesive polymers such as chitosan or carbopol (CP). It has been demonstrated that such delivery systems exhibit increased bioadhesive properties and are capable of improving and prolonging the pharmacological effect of incorporated peptides, such as calcitonin or insulin.3) Another approach is based on the specific bioadhesive properties of lectins. Wheat germ agglutinin (WGA) from Triticum vulgaris is a non-toxic glycoprotein which can specifically bind to Nacetyl-D-glucosamine. 4) This sugar is present on intestinal cells as well as in the intestinal mucus. 5) Recently, it was demonstrated that lectin-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles display increased intestinal bioadhesion and furthermore increase the oral bioavailability of peptide drugs. 6,7) It was the aim of the study to (1) synthesize a novel polymer-lectin conjugate by covalently attaching WGA to carbopol, (2) investigate if the covalent attachment of WGA does decrease or abolish the binding activity of WGA to N-acetyl-D-glucosamine, (3) prepare CP-lectin coated liposomes, and (4) evaluate these coated liposomes concerning intestinal bioadhesion and effect on the oral absorption of incorporated calcitonin. Results and DiscussionThe novel CP-lectin conjugate was synthesized by covalently attaching the amino groups of WGA to the carbodiimide-activated carboxylic groups of carbopol (Fig. 1). Using a spectrophotometric method, the amount of WGA in the purified polymer-lectin conjugate was determined to be 11.79Ϯ 0.8% (mg lectin/100 mg of CP-lectin). To investigate, whether the covalently bound WGA was still capable of binding to N-acetyl-D-glucosamine, a haemagglutination test was performed. N-acetyl-D-glucosamine is, among others, present on the surface of erythrocytes. Therefore, erythrocytes agglutinate in the presence of WGA. Results of this study are shown in Fig. 2. Agglutination was clearly observed in the presence of unbound WGA as well as in the presence of CP-lectin. Contrary, no agglutination was observed in presence of unmodified CP. These results reveal that the novel CP-lectin conjugate is capable of binding to its substrate. Moreover, the comparison of the agglutination behaviour of various concentrations of unbound WGA and CPlectin supports the calculations concerning the amount of WGA in the CP-lectin conjugate gained in the spectrophotometric studies. Next, we investigated if positively charged liposomes can be coated...

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confidence: 99%

Carbopol-Lectin Conjugate Coated Liposomes for Oral Peptide Delivery

2010

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“…Stomach and intestine showed continuous reduction in fluorescence with time while liver and blood showed their maximum fluorescence at 4h followed reduction similarly spleen and kidney showed their maximum fluorescence at 8th hour. Reduction of NPs level in stomach and intestine with time can be attributed to clearance of NPs from the intestine via endocytic uptake through enterocytes and M cell of Peyer's patches and subsequently reached to blood and other body organs (Araujo et al, 1999;Yin et al, 2007;Lalatsa et al, 2012). After stomach and intestine, highest distribution of nanoparticles in liver can be explained by phagocytic uptake of particles due its hydrophobic surface while presence of particles in the renal tissue indicates their renal clearance (Semete et al, 2010(Semete et al, , 2012.…”

Section: Resultsmentioning

confidence: 99%

Improved oral efficacy of epirubicin through polymeric nanoparticles: pharmacodynamic and toxicological investigations

et al. 2016

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Epirubicin (EPI) elicits poor-oral bioavailability hence commercially available as injection for intravenous administration which follows a rapid increase and fast decay in plasma drug concentration often needs a frequent dosing that may lead to serious side effects. Aim of the present study is to develop a nanoparticulate system which could deliver epirubicin effectively via oral administration and could eventually promote new concept ''chemotherapy at home.'' In this perspective, epirubicin loaded Poly-lactide-co-glycolic acid nanoparticles (EPI-NPs) were developed by double emulsion evaporation techniques and evaluated for its safety and efficacy against Ehrlich's Ascites (EAT) induced tumor in balb/c mice. In vivo fate of nanoparticles after oral administration in Albino wistar rats was also studied. EPI-NPs showed marked reduction in tumor size $40% while tumor size was increased 3.55 and 3.28 folds in control as well as in group treated orally with free epirubicin solution (EPI-S), respectively. Furthermore, toxicological evaluation demonstrated insignificant difference in levels of biomarkers including MDA, CAT, SOD, LDH, CK-MB, AST and ALT when EPI-NPs-oral treatment was compared with control group while levels of these biomarkers were found extremely significant in group treated with EPI-S (i.v). and demonstrated increment in LDH (p50.001), CK-MB (p50.001), AST (p50.001), ALT (p50.001) and MDA levels (p50.001) and reduction in SOD (p50.001) and CAT levels (p50.001) thus confirmed better safety profile of EPI-NPs oral than EPI-S i.v. Biodistribution study demonstrated the presence of NPs in different body organs and blood which suggests probability of NPs translocation across intestine thus at the tumor site.

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“…The well-documented biocompatibility and safety of these materials, together with their biodegradability and controlled release capacity (i.e., can sustain slow drug release rates up to several days, weeks or months [100]), has already led to their FDA approval for several clinical applications in humans, and also to a number of marketed products [3]. To improve the active targeting properties of a nanocarrier to specific cells, several surface functionalization approaches have been developed [101][102][103]. The most commonly used method for the preparation of PLA/PLGA NPs is the double emulsion-solvent evaporation method using dichloromethane or ethyl acetate as the polymer solvent.…”

Section: Polymeric Carriersmentioning

confidence: 99%