Thirdly, bioadhesion could also localize the PMs at a given target site and increase the drug concentration gradient for the intense contact of the particles with the mucosal surface [27]. The ability to develop mucoadhesive interactions within the gut would be one of the key factors influencing their ability to promote oral absorption of the loaded drug. It was demonstrated that there Carfilzomib molecular weight exists a direct relationship between mucoadhesion and drug absorption [114, 115]. In fact, the development of adhesive interactions (between PMs and mucosa) would probably induce the immobilization of these carriers

in intimate Inhibitors,research,lifescience,medical contact with the absorptive membrane. This fact would facilitate the establishment of a concentration gradient of the loaded drug from the PMs to the circulation, which finally results in an enhancement of absorption and bioavailability. 4.3.2. Mechanisms of Mucoadhesive PMs for Enhancement of Bioavailability Mucoadhesion is a complex phenomenon, Inhibitors,research,lifescience,medical and several steps have Inhibitors,research,lifescience,medical been suggested in mucoadhesive bond formation [116]. The first step is the spreading, wetting, and dissolution of mucoadhesive polymer at the interface. The second step is the mechanical or physical entanglement between the polymer and the tissue surface mucus layer, resulting in an interpenetration

layer. The next step is the result of chemical interactions [116]. Mucoadhesion can be obtained by the building of either nonspecific interactions with the mucosal surface, such as covalent

bonds, ionic bonds, hydrogen bonding, Inhibitors,research,lifescience,medical and van der Waals’ interactions [117], or specific interactions by functionalizing polymers with targeting ligands (e.g., lectins [118, 119]) or reactive groups such as thiols [120]. The fates of the mucoadhesive PMs in the GI tract include at least three different pathways: mucoadhesion, Inhibitors,research,lifescience,medical translocation through the mucosa or transit, and direct faecal elimination. Among the various factors, the surface charges of PMs seem to play an important role in particle uptake. On one hand, the negatively charged intestinal mucosa, due to the existence of glycocalyx, attracts more positively charged PMs. Therefore, a considerable selleck chemicals llc number of studies have been conducted using positively charged polymers such as chitosan to increase residence time in the GI tract [121, 122]. Entinostat On the other hand, the particle mobility also seems to be strongly dependent on surface charges, and it was indicated that transport rates were inversely related to particle surface potentials. Negatively charged particles display significantly higher transport rates than near neutral or positively charged particles whose transport was probably limited by particle aggregation and electrostatic adhesive interactions with mucosa [123].