Mucoadhesion chitosans

Chitosan Mucoadhesive, permeation enhancing, high buffer capacity Takeuchi et al. (1994) and Luessen et al. (1996a)... 

Keywords Chitosan Mucoadhesion Particles Permeation enhancement Thiomers... 

Deacon, M. R, McGurk, S., Roberts, C. J., et al. Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. J. Biochem. 2000,348,557-563. 

A number of articles considered the association of chitosan with polylactic acid or similar compounds [47-49] another group of articles presented new data on highly cationic chitosans [ 50 - 55]. More data have also been made available on the delivery of growth factors [56] and ophthalmic drugs [57,58], on the activation of the complement, macrophages [59-61] and fibroblasts [62], on mucoadhesion [63] and functionalization of chitin [64]. The development of new carriers for the delivery of drugs, and the interactions of chitosans with living tissues seem therefore to be major topics in the current research on chitosan. Therefore, this chapter will place emphasis on these aspects. 

Fig. 10 Sedimentation analysis of the comparative mucoadhesiveness of a chitosan (sea cure 210+, Fa 0.11) to mucins from different parts of the stomach a Mucin source b Histogram. Adapted from [151]...

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). 

The mucoadhesive properties of several classes of hydrogels have been identified, and two types of polymers have attracted special attention. Polyacrylates and their cross-linked modifications represent the anionic type, chitosan and its derivatives the cationic group. In addition, both types of polymers show a number of interesting characteristics beneficial for the administration of a wide range of therapeutics. 

The periodontal pocket is another site for drug delivery in the oral cavity. Needleman et al. [46] investigated three mucoadhesive polymers (cationic chitosan, anionic xanthan gum, neutral polyethylene oxide) in vitro, using organ cultures, and in vivo in patients on their periodontal and oral mucosa. Of the polymers studied, chitosan displayed the longest adhesion in vitro and on the periodontal pockets, and the shortest adhesion on oral mucosa. 

Another trend observed during the past decade was the coating of liposomes with mucoadhesive polymers. Liposomes are coated with chitosan, long-ehain polyvinyl alcohol, and polyacrylates bearing a cholesteryl group [90]. Chitosan-eoated liposomes showed superior adhesion properties to rat intestine in vitro than the other polymer-eoated liposomes. In vivo, chitosan-coated liposomes containing insulin substantially reduced blood glueose levels after oral administration in rats, whieh were sustained up to 12 hr after administration [90]. 

Remunan-Lopez, C., Portero, A., VilaJato, J.L., and Alonso, M.J., Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery, J. Control. Rel., 55 143-152 (1998). 

LueBen, H.L., Rentel, C.O., Kotze, A.F., Lehr, C.-M., De Boer, A.G., Verhoef, J.C., and Junginger, HE., Mucoadhesive polymers in peroral peptide drug delivery. 4. Polycarbophil and chitosan are potent enhancers of peptide transport across intestinal mucosae in vitro, J. Control Rel, 45 15-23 (1997). 

Bernkop-Schnurch A., and Krajicek, M.E., Mucoadhesive polymers as platforms for peroral peptide delivery and absorption synthesis and evaluation of different chitosan-EDTA conjugates, J. Control. Rel., 50 215-223 (1998). 

Takeuchi, H., Yamamoto, H., Niwa, T., Hino, T., and Kawashima, Y., Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes, Pharm. Res., 13 896-901 (1996). 

In vitro and ex vivo intestinal tissue models to measure mucoadhesion of poly (methacrylate) and N-trimethylated chitosan polymers. Pharmaceutical Research, 22, 38-49. 

Filipovic-Grcic, J., Skalko-Basnet, N., and Jalsenjak, I. (2001). Mucoadhesive chitosan-coated liposomes Characteristics and stability. ]. Microencapsul. 18, 3-12. 

Lehr, C.M., et al. n vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers,Int. J. Pharm., 78, 43, 1992. 

Roldo, M., et al., Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery synthesis antfi vitro evaluation,Eur. J. Pharm. Biopharm., 57, 115, 2004. 

Drug release and retention at the site of absorption are very important for the enhancement of the bioavailability, particularly when the absorption sites are localized to a certain area of the GI route. This control of the transition of the drug can be achieved using bioadhesive excipients. Chlorothiazide (CT), a diuretic and antihypertensive drug, was better orally absorbed when administered with mucoadhesive polymers [25], The absorption of CT is considered to be saturable and site-specific, because a low dose is better absorbed, and a decreased stomach emptying rate and slow GI transition rate are better for increased absorption. As chitosan is a mucoadhesive polymer, the absorption of CT is expected to be enhanced... 

Chitosan not only displays mucoadhesive properties, but also acts as an absorption enhancer in the intestinal cell layer membrane [34,35]. The mucoadhesion raises the concentration of... 

Multilamellar liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dicetyl phosphate (DCP) were prepared by the formation of a thin lipid film and subsequent sonication, and coated with chitosan (Ch) [36], Liposomes with a size of approximately 5 pm were used in the experiment. The Ch-coated and plain liposomes were compared in terms of mucoadhesion to the rat stomach and intestinal parts. Although both the liposomes were less adhesive to the stomach, Ch-coated liposomes displayed much higher mucoadhesion to all the intestinal parts in vitro than the plain liposomes. The intestinal adhesion of the plain liposomes were minimal. Further, Ch-coated liposomes showed a great mucoadhesion to the intestine at acidic and neutral pH values. This was also confirmed by fluorescence microscopy when pyrene-loaded Ch-coated liposomes were used in the mucoadhesion test. 

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