Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs

Merwe, Susanna M. van der; Verhoef, J.; Verheijden, J.H.M.; Kotzé, A.F; Junginger, Hans E.

doi:10.1016/j.ejpb.2004.03.023

Cited by 238 publications

(60 citation statements)

References 34 publications

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“…8 TMC particles prepared via chemical cross-linking can be potentially toxic and the nanoparticles could also chemically modify the entrapped proteins. 15 Therefore, physical techniques, similar to spray drying and ionic cross-linking, are considered relatively more suitable and conservative for protein. TMC nanoand micro-particles have been fabricated by ionic cross-linking with different polyanions, such as polyglutamic acid, TPP, sodium sulfate, dextran sulfate, and anionic cyclodextrins.…”

Section: Discussionmentioning

confidence: 99%

“…Then, the polymer was precipitated, washed twice with acetone, and dried at room temperature. 15,16 Characterizing TMC by 1 H-NMR spectroscopy The TMC synthesized in this study was characterized by 1 Hnuclear magnetic resonance ( 1 H-NMR) spectroscopy. The NMR spectra of the solution of 5 mg of TMC in 700 mL of D 2 O (dissolved by heating at 80 C) were acquired.…”

Section: Methodsmentioning

confidence: 99%

“…Then, the tubes were incubated at 37 C under constant shaking. One tube was removed at specific intervals (15,30,60,90,120,240,360,1440, and 1800 min) and centrifuged at 65,000g and 4 C for 30 min. The amount of HBsAg released into the supernatant was then measured.…”

Section: Hbsag Loading Efficiency and Loading Capacity Of Nanoparticlesmentioning

confidence: 99%

“…Therefore, chitosan derivatives with enhanced solubility at basic and neutral pH are essential. [12][13][14][15] It has been shown that TMC, a quaternary derivative of chitosan, enhances penetration and opens epithelial tight junctions in the environments with basic and neutral pH. 14 The gastric enzymes and acidic conditions pose challenges to the oral administration of vaccines.…”

Section: Introductionmentioning

confidence: 99%

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Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery

Farhadian

Dounighi

Avadi³

2015

Human Vaccines & Immunotherapeutics

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Oral vaccination is the preferred route of immunization. However, the degradative condition of the gastrointestinal tract and the higher molecular size of peptides pose major challenges in developing an effective oral vaccination system. One of the most excellent methods used in the development of oral vaccine delivery system relies on the entrapment of the antigen in polymeric nanoparticles. In this work, trimethyl chitosan (TMC) nanoparticles were fabricated using ionic gelation teqnique by interaction hydroxypropyl methylcellulose phthalate (HPMCP), a pHsensitive polymer, with TMC and the utility of the particles in the oral delivery of hepatitis B surface antigen (HBsAg) was evaluated employing solutions that simulated gastric and intestinal conditions. The particle size, morphology, zeta potential, loading capacity, loading efficiency, in vitro release behavior, structure, and morphology of nanoparticles were evaluated, and the activity of the loaded antigen was assessed. Size of the optimized TMC/HPMCP nanoparticles and that of the antigen-loaded nanoparticles were 85 nm and 158 nm, respectively. Optimum loading capacity (76.75%) and loading efficiency (86.29%) were achieved at 300 mg/mL concentration of the antigen. SEM images revealed a spherical shape as well as a smooth and near-homogenous surface of nanoparticles. Results of the in vitro release studies showed that formulation with HPMCP improved the acid stability of the TMC nanoparticles as well as their capability to preserve the loaded HBsAg from gastric destruction. The antigen showed good activity both before and after loading. The results suggest that TMC/HPMCP nanoparticles could be used in the oral delivery of HBsAg vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Hbsag Loading Efficiency and Loading Capacity Of Nanoparticlesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery

Farhadian

Dounighi

Avadi³

2015

Human Vaccines & Immunotherapeutics

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“…It was reported that TMC acted on epithelial cell monolayers by opening the tight junctions between adjacent cells through an interaction of the polycationic polymers with the negatively charged sites on the cell membrane and/or in the tight junctions. Such an action would favor time dependent decrease in the TEER and paracellular drug transport (van der Merwe et al, 2004a, Di Colo et al, 2004. Moreover, TMC-Arg8-Lips showed sustained decrease effect on the TEER and only 70% of original TEER was found after 2 h incubation, which was 1.14-and 1.21-fold lower than that of FD4 þ TMC solution and TMCLips, respectively.…”

Section: Teer Of Caco-2 Cell Monolayer and The Permeation Of Fd4mentioning

confidence: 96%

Oral absorption enhancement of salmon calcitonin by using bothN-trimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers

Huang

et al. 2013

Drug Delivery

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In this study both N-trimethyl chitosan chloride (TMC) and oligoarginine (Arg8) were utilized to modify liposomes as the multifunctional carriers (TMC-Arg8-Lips) for enhancing the oral absorption of salmon calcitonin. Two permeation enhancers with positive charges were sequentially adsorbed on the liposomal surface with negative charges by electrostatic interaction. Instead of salmon calcitonin, fluorescein isothiocyanate dextran (FD4) was loaded in TMC-Arg8-Lips for Caco-2 cell permeation test in vitro and penetration examination in rat intestinal tract in vivo. The results showed that the apparent permeability coefficient (P app ) of TMC-Arg8-Lips containing FD4 were 7.0-, 4.4-, 1.8-and 1.4-folds higher than FD4 solution, FD4-TMC solution, non-modified liposomes (Non-Lips) and TMC modified liposomes (TMC-Lips), respectively. A strong fluorescence was observed by confocal laser scanning microscope (CLSM) at rat intestinal wall isolated in different times after the FD4 loaded carriers were intragastrically administrated. Furthermore, the images revealed that TMC-Arg8-Lips could penetrate deeply inside the mucosal membrane. The pharmacodynamic study indicated that TMC-Arg8-Lips containing calcitonin were more efficient in enhancing the absorption and prolonging the reduction of blood calcemia in rats. The area above the plasma calcium concentration-time curve (AAC) of TMC-Arg8-Lips containing calcitonin was increased by more than 16.6-and 1.6-fold when compared to Non-Lips and TMC-Lips, respectively.

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Polymer‐Based Delivery Systems for Oral Delivery of Peptides and Proteins

Sarmento

Ferreira

Vasconcelos

2009

Delivery Technologies for Biopharmaceuticals

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Trimethylated chitosan as polymeric absorption enhancer for improved peroral delivery of peptide drugs

Cited by 238 publications

References 34 publications

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery

Enteric trimethyl chitosan nanoparticles containing hepatitis B surface antigen for oral delivery

Oral absorption enhancement of salmon calcitonin by using bothN-trimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers

Polymer‐Based Delivery Systems for Oral Delivery of Peptides and Proteins

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