The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. III: Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro

Borchard, Gerrit; Lueβen, Henrik L.; Boer, Albertus G. de; Verhoef, J.; Lehr, Claus‐Michael; Junginger, Hans E.

doi:10.1016/0168-3659(95)00146-8

Cited by 370 publications

(140 citation statements)

References 18 publications

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“…In recent years, the most frequently explored polysaccharide for the design of nanodelivery systems was chitosan, a cationic polymer composed of repeating β-(1,4)-linked N-acetylglucosamine and D-glucosamine units, which is obtained by chitin deacetylation and assumes different molecular weights and deacetylation degrees (Chiellini et al, 2008;Hassani et al, 2012;Mizrahy and Peer, 2012). Apart from the reported biocompatibility and biodegradability (Dornish et al, 1997;Grenha et al, 2010a;Hirano et al, 1988), the most outstanding properties of chitosan rely on its mucoadhesive character (Lehr et al, 1992) and demonstrated ability to potentiate transmucosal absorption both as molecule (Artursson et al, 1994;Borchard et al, 1996;Portero et al, 2002) and in the form of nanoparticle (Al-Qadi et al, 2012;De Campos et al, 2001;Fernández-Urrusuno et al, 1999a;Prego et al, 2005a;Yamamoto et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Dionísio

Cordeiro

Remuñán‐López

et al. 2013

European Journal of Pharmaceutical Sciences

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Polymeric nanoparticles have revealed very effective in transmucosal delivery of proteins. Polysaccharides are among the most used materials for the production of these carriers, owing to their structural flexibility and propensity to evidence biocompatibility and biodegradability. In parallel, there is a preference for the use of mild methods for their production, in order to prevent protein degradation, ensure lower costs and easier procedures that enable scaling up.In this work we propose the production of pullulan-based nanoparticles by a mild method of polyelectrolyte complexation. As pullulan is a neutral polysaccharide, sulfated and aminated derivatives of the polymer were synthesized to provide pullulan with a charge. These derivatives were then complexed with chitosan and carrageenan, respectively, to produce the nanocarriers. Positively charged nanoparticles of 180-270 nm were obtained, evidencing ability to associate bovine serum albumin, which was selected as model protein. In PBS pH 7.4, pullulan-based nanoparticles were found to have a burst release of 30% of the protein, which maintained up to 24h. Nanoparticle size and zeta potential were preserved upon freeze-drying in the presence of appropriate cryoprotectants. A factorial design was approached to assess the cytotoxicity of raw materials and nanoparticles by the metabolic test MTT. Nanoparticles demonstrated to not cause overt toxicity in a respiratory cell model (Calu-3). Pullulan has, thus, demonstrated to hold potential for the production of nanoparticles with an application in protein delivery.

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Section: Introductionmentioning

confidence: 99%

Pullulan-based nanoparticles as carriers for transmucosal protein delivery

Dionísio

Cordeiro

Remuñán‐López

et al. 2013

European Journal of Pharmaceutical Sciences

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“…1 However, oral administration of protein drugs also has certain obstacles, as drugs must overcome various significant barriers in the gastrointestinal (GI) tract prior to delivery to the bloodstream. 2,3 First of all, protein drugs are readily degraded by the low pH of gastric medium in the stomach. Second, different digestive enzymes in the stomach and small intestine may lead to degradation of protein drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Second, different digestive enzymes in the stomach and small intestine may lead to degradation of protein drugs. [3][4][5] Therefore, a carrier system is required to protect protein drugs from the GI environment.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Characterization of Nanoparticles Shelled with Chitosan for Oral Insulin Delivery

et al. 2006

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Nanoparticles (NPs) composed of chitosan (CS) and poly(γ-glutamic acid) (γ-PGA) were prepared by a simple ionic-gelation method for oral insulin delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and γ-PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the crystal structure of CS was disrupted after it was combined with γ-PGA. The diameters of the prepared NPs were in the range of 110-150 nm with a negative or positive surface charge, depending on the relative concentrations of CS to γ-PGA used. The NPs with a positive surface charge (or shelled with CS) could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. After loading of insulin, the NPs remained spherical and the insulin release profiles were significantly affected by their stability in distinct pH environments. The in vivo results clearly indicated that the insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic rat model.

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“…Various studies carried out on Caco-2 cell monolayers demonstrated a significant decrease in the transepithelial electrical resistance after the addition of chitosan [25][26][27] . The mechanism underlying this permeation enhancing effect seems to be based on the positive charges of the polymer which interact with the cell membrane resulting in a structural reorganization of tight junction-associated proteins 28 .…”

Section: Permeation Enhancing Effectmentioning

confidence: 99%