Mucoadhesive propertie enhancers

In recent studies both in vitro (Caco-2 cells) and in vivo in rats, TMC with a degree of trimethylation of 60% was proven to be an excellent intestinal absorption enhancer of the peptide drugs buserelin and octreotide. The observed absolute bioavailability values were 13 and 16% for buserelin and octreotide, respectively [83] (impublished data Fig. 5). Permeation enhancing effects were more responsible for these increased bioavailabilities, rather than the mucoadhesive properties of the TMC polymers. Nevertheless, mucoadhesion is a prerequisite for these polymers in order to further act as absorption enhancers. 

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... 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

In a recent study, some authors proposed the employment of thiolated polymers obtained by the immobilization of thiol groups on well-established multifunctional polymers such as poly(acrylates) and chitosans as functional agents having mucoadhesive, penetration enhancement, and enzyme-inhibiting properties [94,95]. 

Finally, it should be noted that during the last decade both weakly crosslinked poly(acrylic acid) derivatives and chitosan derivatives were described as safe penetration enhancers for hydrophilic compounds especially as they can trigger mechanisms of tight junction opening of mucosal tissues and did not show acute toxicity. Poly(acrylic acid) derivatives were shown to have excellent mucoadhesive properties and can inhibit the activity of gut enzymes, such as trypsin, chymo-trypsin, and carboxypepsidases. Chitosan salts and Ni-trimethylchitosan chloride revealed to be potential absorption enhancers for nasal absorption of calcitonin and insulin and for the intestinal absorption of buserilin.f ... 

The third class of permeation enhancers are the polymeric enhancers. In comparison to the LMM, these provide additional advantages as they can often also be used as a particle-forming carrier. Additional mucoadhesive properties keep the delivery systems in the area of drug adsorption [108]. The best known example for cationic polymers is chitosan. The enhancing effect for poorly absorbable drugs has been shown in cell models, as well as in rats. It is assumed that... 

Anionic polymeric permeation enhancers have a different effect. They do not interact directly with the membrane, but bind and deplete Ca ions from the extracellular cell medium, which leads to an opening of the tight junctions [111]. The properties of anionic polymers have also been improved. By immobilization of free sulf-hydryl groups onto various polymers, their permeation-enhancing effect on hydrophilic compounds is strongly increased [112]. In addition, thiolated polymers (thiomers) show improved mucoadhesive properties which allows them to concentrate in the area of drug absorption [113]. 

Reduction of the disulfide bond in the thiol-rich environment, resulting in the release of the entrapped protein, was also the working principle of another intracellular protein delivery system. The DDS was based on linear polyamidoamines (PAAs) that formed a PEC with negatively charged human serum albumin (HSA). The PEC showed mucoadhesive properties and released the immobilized HSA under intracellular conditions due to the cleavage of the disulfide bonds, while the complex was stable under extracellular conditions. This resulted in enhanced uptake by exposed human-derived intestinal Caco-2/TC7 cells and HT29-MTX mucus/ secreting cells. 

Due to the presence of variable compounds in the natural sources from which chitin and chitosan are extracted, the physical and chemical properties of both chitin and chitosan vary remarkably. Chitosan has been described as a nontoxic, biodegradable, and biocompatible polymer with very interesting biological properties, such as permeation-enhancing and mucoadhesive properties, anticoagulant and antimicrobial activity and so on. The properties of chitosan are greatly affected by the conditions under which it is processed, because it is the process conditions that... 

The mucoadhesive property of chitosan has been exploited in designing various mucoadhesive dosage forms as it prolongs the contact time of the active drug at its requisite site of absorption, thus often enhancing its bioavailabihty and exhibiting a sustained drug release effect [112-114]. 

E. Karavas, E. Georgarakis, D. Bikiaris, Application of PVP/HPMC miscible blends with enhanced mucoadhesive properties for adjusting drug release in predictable pulsatile chronotherapeutics, Eur J Pharm Biopharm, 64 (1), 115-126, 2006. 

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