Chitosan absorption-enhancing effect

Ilium et al. [49] evaluated chitosan solutions as delivery platforms for nasal administration of insulin to rats and sheep. They reported a concentration-dependent absorption-enhancing effect with minimal histological changes of the nasal mucosa in all concentrations applied. 

Fetih, G., et al. 2005. Improvement of absorption enhancing effects of /j-dodecyl-beta-D-maltopyr-anoside by its colon-specific delivery using chitosan capsules. Int J Pharm 293 127. 

Therefore, the enhancement of transport is not accompanied by damage to the cells, which is superior to the absorption-enhancing effects of other small molecules, which lead to irreversible changes in the cell membrane and damage to the cell. Thus, much attention has been paid to chitosan as a polymeric substance that enhances GI absorption. 

Chitosan and its derivatives have been applied to enhance the absorption of proteins (e.g., insulin) and polypeptides (e.g., buserelin). /V-Trimethyl chitosan chloride exhibits opening of the tight junctions of the intranasal and intestinal epithelial cells so that the transport of hydrophilic compounds is increased through the para-cellular transport pathway. The absorption-enhancing effect was concentration dependent and reversible and dependent on the integrity of the intercellular cell contact zone. 

Chitosan-based nano- and microparticles are widely used for fabrication of controlled dmg release systems. Numerous studies have demonstrated that chitosan and its derivatives (A-trimethyl chitosan, mono-A-carboxymethyl chitosan, etc.) are effective and safe for absorption enhance to improve mucosal (nasal, peroral) delivery of hydrophylic macromolecules, such as peptide and protein dmgs as well as heparins [37,38]. This absorption enhancing effect of chitosan is caused by the opening of intercellular tight junctions, thereby favoring the paracellular transport of macro-molecular dmgs. Recently, a series of successful model chitosan-based polymer systems for mucosal dmg delivery have been reported. Thus, Lim et al. [39] have proposed novel polymer microparticles based on combination of hyaluronic acid and chitosan hydroglutamate... 

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

Borchard, G. LueBen, H.L. deBoer, A. G. Verhoef, J. C. Lehr, C.-M. Junginger, H.E., The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption. Ill Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro, j. Control. Rel. 39, 131-138 (1996). 

Aspden, T.J., L. Ilium, and O. Skaugrud. 1996. Chitosan as a nasal delivery system Evaluation of insulin absorption enhancement and effect on nasal membrane integrity using rat models. Eur J Pharm Sci 4 23. 

Sadeghi, A.M.M., Dorkoosh, F.A., Avadi, M.R., Bayat, A., Delie, F., Gurny, R., Rafieeh-Tehrani, M. and Junginger, H.E. (2008a) Permeation enhancer effect of chit-osan and chitosan derivatives comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells. Eur. J. Pharm. Bio-pharm. 70 270-278. 

Thanou, M., Verhoef, J.C. Romeijn, S.G., Nagelkerke, J.F., Merkus, F.W.H.M. and Junginger, H.E. (1999) Effects of A-trimethyl chitosan chloride, a novel absorption enhancer, on Caco-2 intestinal epithelia and the ciliary beat frequency of chicken embryo trachea. Int. J. Pharm. 185 73-82. 

Since the concentrations of insulin to be administered in the sheep model would have been large, the insulin-loaded chitosan nanoparticles were not investigated in that model. However, the pharmacodynamics and pharmacokinetics of various insulin-chitosan preparations were compared with postloaded insulin-chitosan nanoparticles. It was found that chitosan solution and chitosan powder formulations were far better, with the chitosan powder formulation showing a bioavailability of 17% as against 1.3 and 3.6% for the chitosan nanoparticles and chitosan solution [72], The effects of the concentration and osmolarity of chitosan and the presence of absorption enhancers in the chitosan solution on the permeation of insulin across the rabbit nasal mucosa in vitro and in vivo were investigated, and the same... 

Besides the polymer derivatization, combining the polymers in microsphere preparations can result in improved drug delivery and absorption characteristics. Hyaluronic acid-chitosan microspheres appeared to improve the absorption of incorporated gentamicin compared to the individual polymers, assembling the mucoadhesive potential of both polymers and the penetration-enhancing effect of chitosan [51,52],... 

To increase the residence time in the nasal mucosa, a bioadhesive formulation may be one of the most reasonable approaches. In fact, microspheres containing bioadhesive polymers such as starch, albumin, and Sephadex with a particle size of 40-60 pm have been found to be cleared from the nasal cavity much more slowly than solutions. Starch microspheres improved the nasal absorption of insulin, with synergistic effects of some absorption enhancers in sheep. In another paper, dry powder containing starch and Carbopol 974P showed significantly higher bioavailability after nasal administration than the formulation without Carbopol. ° Chitosan, already mentioned above, also has a bioadhesive property and is found to be useful as a potent absorption enhancer for nasal peptide delivery. Other bioadhesive polymer systems,... 

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