Development and In Vitro Characterization of Liposomes Coated with Thiolated Poly(Acrylic Acid) for Oral Drug Delivery

Werle, Martin; Hironaka, Kohei; Takeuchi, Hirofumi; Hoyer, Herbert

doi:10.1080/03639040802244326

Cited by 20 publications

(9 citation statements)

References 17 publications

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“…In the present work, we aimed to gain insight into the internalization and cellular traffic of multillamelar PLCs in epithelial like cells. We selected the use of multilamellar liposomes based on their high efficiency of encapsulation and a relative slow release of the entrapped compounds [23,24]. On the contrary, small unilamellar liposomes usually have a very weak capacity to trap drugs and usually exhibited a burst release of its content [23,24].…”

Section: Discussionmentioning

confidence: 99%

Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes in human epithelial-like cells

Szymanowski

Hugo

Alves

et al. 2017

Colloids and Surfaces B: Biointerfaces

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Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs. The aim of the present work is to study the mechanisms of cellular uptaking and the intracellular trafficking of PLCs formed with cholesterol-poly(2-(dimethylamino)ethyl methacrylate) CHO-PDMAEMA and lecithin (LC CHO-PD). Calcein-loaded liposomes were used to determine cellular uptake and intracellular localization by flow cytometry and confocal microscopy. Incorporation of CHO-PDMAEMA to lecithin liposomes enhanced the internalization capacity of PLCs. Internalization of PLCs by human epithelial-like cells (HEK-293) diminished at 4°C, suggesting uptake by endocytosis. PLCs showed no co-localization with acidic compartments after internalization. Experiments with endocytosis inhibitors and co-localization of liposomes and albumin, suggested the caveolae endocytic pathway as the most probable route for intracellular trafficking of PLCs. In this work, we demonstrated an efficient uptake of LC CHO-PDs by human epithelial-like cells (HEK-293) through the non-degradative caveolae endocytic pathway. The mode of internalization and the intracellular fate of liposomes under study, suggest a promising use of LC CHO-PDs as drug delivery systems.

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Section: Discussionmentioning

confidence: 99%

Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes in human epithelial-like cells

Szymanowski

Hugo

Alves

et al. 2017

Colloids and Surfaces B: Biointerfaces

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“…9) Cationic multilamellar liposomes (MLV) consisting of For in vivo absorption studies, calcitonin was added to the hydration medium. Finally, the liposome suspension was incubated for 30 min at 10°C.…”

Section: Methodsmentioning

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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“…Excess TK and curcumin were then removed by ultracentrifugation (Remi, India) at 2000 rpm for 30 min followed by a single washing with distilled water. The resulting TK-coated liposomes (TKF8) were resuspended in phosphate buffer solution 13.…”

Section: Preparation Of Thiolated Karaya Gum Coated Liposomes Loaded mentioning

confidence: 99%

Formulation and Evaluation of Curcumin Loaded Thiolated Polymer Coated Liposomes for Aphthous Ulcers

Munot¹,

Gujar²

2019

Int. Res. J. Pharm.

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Aphthous ulcers or Recurrent Aphthous Stomatitis (RAS) are inflammatory lesions of mucous lining of mouth associated with redness, swelling and occasional bleeding from affected area(s). Curcumin, a herbal drug was selected due to its antioxidant, anti-inflammatory, antimicrobial and wound healing ability. Present study deals with formulation, optimization and evaluation of curcumin loaded liposomes for local drug delivery as liposomes have property to get concentrated in inflamed areas. Efficacy of liposomes was enhanced in terms of mucoadhesion, retention in the buccal mucosa and sustained release of drug by coating them with Thiolated Karaya gum. Curcumin loaded liposomes, prepared using thin film hydration method were optimized by 3 2 factorial design using Design Expert Software. Batch F8 having entrapment 75.1±0.94 % and controlled the release of curcumin up to 12 h was considered optimized and was coated with thiolated karaya gum to get TKF8. Successful coating was evident from TEM images, increase in particle size from 129.86 ± 9.1 nm to 152.39 ± 1.3 nm, zeta potential from negative to positive -10.5 mV to 9.55mV. TKF8 showed better mucoadhesion by absorbing 6.98 % more amount of mucin and also had ability to concentrate in the buccal mucosa for 24 h as observed using exvivo studies. It can be attributed to positively charged thiolated polymer interacting with negatively charged sialic acid residues in the mucus. Drug release from F8 and TKF8 was sustained for 12 h and 24 h respectively and they followed diffusion controlled release (Peppas model). This formulation can be efficient therapeutic strategy for apthous ulcers which would provide relief to the patients.

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Development and In Vitro Characterization of Liposomes Coated with Thiolated Poly(Acrylic Acid) for Oral Drug Delivery

Cited by 20 publications

References 17 publications

Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes in human epithelial-like cells

Endocytosis and intracellular traffic of cholesterol-PDMAEMA liposome complexes in human epithelial-like cells

Carbopol-Lectin Conjugate Coated Liposomes for Oral Peptide Delivery

Formulation and Evaluation of Curcumin Loaded Thiolated Polymer Coated Liposomes for Aphthous Ulcers

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