Sodium alginate-guar gum and carbopol based methotrexate loaded mucoadhesive microparticles for colon delivery: An in vitro evaluation

Methotrexate (MTX) is famous for its therapeutic potential against different cancers including colorectal cancer. Goal of the present investigation was to formulate MTX loaded mucoadhesive microparticles for colon targeting. The optimized formulation (MTX-MS2) was composed of mucoadhesive polymers (sodium alginate, guar gum and carbopol 940) in an appropriate ratio. MTXMS2 was developed by ionic-gelation method. The suitable particle size and zeta potential were found to be 21.10 ± 0.18 µm and 3.01 ± 0.16 mV for MTX-MS2 respectively. The % yield (98.60 ± 2.12), % entrapment efficiency (97.98 ± 1.22) and % drug loading (1.04 ± 0.03) were estimated for MTXMS2. The swelling index (0.99 ± 0.04 θ) and mucoadhesion (97.29 ± 4.61%) were significantly (***P ˂ 0.01) achieved with MTX-MS2 as compared to other formulations. The optimum drug release (96.07 ± 4.52%) was significantly achieved with MTX-MS2 at simulated gastric fluid (pH 7.4) for 36 h in a sustained manner. This profile may be attributed towards excellent mucoadhesivness of the polymers used in the formulation. Therefore, the current investigation suggests that mucoadhesive carrier system could be promising approach for colon delivery. Thus, the proposed work would be helpful for the treatment of colorectal canc

Screening and Characterization of Antimalarial Heme Polymerase Inhibitors from Garlic Cloves.

Aim: Garlic (Allium sativum L) aqueous extract was investigated to identify antimalarial compounds inhibiting heme polymerization. Methods: Solvent fraction of aqueous garlic extract was tested in heme polymerization assay and antimalarial assay to identify active factor. Mass spectroscopy, TLC and optical spectroscopy was used to characterize the active factor and mechanism of inhibiton. Results: Solvent fractionation and silica chromatography of aqueous garlic extract yields partially purified active constituent. The crude garlic extract has a high level of heme polymerization inhibition activity. Mass spectroscopy analysis of the high activity fraction indicates quercetin as a promising hit with an acceptable limit of error. Pure quercetin was found to inhibit heme polymerization and inhibit parasite growth in a dose dependent manner with an activity comparable to the activity present in the purified garlic aqueous fractions. Quercetin forms two distinct complexes with hemin as evident by TLC Chromatogram of hemin and quercetin mixture. ESI-MS analysis of quercetin-hemin reaction mixture gives two prominent peaks; 1st peak with m/z 929 (Hemin+Q+Li+3H) and 2nd peak with m/z 1244.7 (H+2Q+Na) with a clear indication of the formation of quercetin: hemin (1:1) and 2:1 complexes. The dissociation constant (Kd) of quercetin-hemin is 9.35 μM. Conclusions: In summary, aqueous garlic extract has heme polymerization inhibitor with high antimalarial activity. Quercetin is the main active constitution responsible for the activity and it inhibits heme polymerization by chelating free available hemin for polymerization.