Some other groups have also developed the pH-sensitive oral drug delivery systems. In an earlier report, Sant et al. prepared and characterized a pH-sensitive PMs incorporating poorly water-soluble model drugs [104]. The

self-assemblies were constructed from novel pH-sensitive polymers composed of poly(ethylene glycol)-block-poly(alkyl acrylate-co-methacrylic acid) (PEG-b-P(AlA-co-MAA)). Due to the presence of pendant carboxyl groups in the hydrophobic part, these copolymers exhibit pH-dependent aggregation Inhibitors,research,lifescience,medical behavior and form supramolecular micelles below pH 4.7. Hence, these copolymers dissociate partially or completely with increase in pH owing to the ionization of carboxylic groups. Two water-insoluble model drugs,

named indomethacin (IND) and fenofibrate (FNB), were incorporated in the supramolecular assemblies by dialysis or oil-in-water (O/W) emulsion methods. The pH-dependent drug release in vitro from the micelles Inhibitors,research,lifescience,medical was also confirmed in their study. To make sure whether pH-sensitive PMs could improve the bioavailability of a poorly water-soluble drug, further in vivo study was carried out [1]. For in vivo study, FNB was chosen as the poorly water-soluble model drug. The pharmacokinetics of FNB incorporated in PMs was evaluated in male Sprague-Dawley rats after oral dosing and compared with the commercial micronized formulation, Lipidil MicroR Inhibitors,research,lifescience,medical and an FNB www.selleckchem.com/products/mek162.html coarse suspension. The oral bioavailability of FNB from these self-assemblies revealed 156% and 15% increases versus FNB coarse suspension and Lipidil MicroR, respectively. The results suggest that these pH-sensitive PMs could efficiently improve the bioavailability Inhibitors,research,lifescience,medical of poorly water-soluble drugs. Other types of pH-controlled release carriers such as pH-sensitive polymer-drug conjugates [107, 108] are beyond the scope of PMs and not discussed in this review. 4.3. Mucoadhesive PMs for Enhancement of Bioavailability 4.3.1. Introduction Inhibitors,research,lifescience,medical of Mucoadhesive PMs Nanocarriers for oral administration

should adhere to mucus and cross the mucus layer. Drugs delivered to mucosal surfaces are usually efficiently removed by mucus clearance mechanisms [109]. The luminal surface of mucosal Vismodegib solubility tissues is protected by a highly viscoelastic layer [110], and the protective coatings rapidly remove foreign particles from the GI tract which probably lead to low bioavailability. Unlike the relatively high requirements of intravenous GSK-3 infusions, oral formulations could include high-molecular weight polymers as long as these components are metabolizable and cannot find their way into the systemic circulation. Hence, it may be an effective means of increasing uptake of drugs with mucoadhesive PMs [111, 112], and there have been considerable interests in the concept of mucoadhesive PMs. Firstly, mucosal retention can be used to increase the transit time in the GI tract, resulting in prolonged time window for the release of the payload.