Browsing by Author "Dawoud, Marwa H. S"

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    An approach for an enhanced anticancer activity of ferulic acid-loaded polymeric micelles via MicroRNA-221 mediated activation of TP53INP1 in caco-2 cell line
    (Nature Publishing Group, 2024-01) Sweed, Nabila M; Dawoud, Marwa H. S; Aborehab, Nora M; Ezzat, Shahira M
    Ferulic acid (FA) has powerful antioxidant and antitumor activities, but it has low bioavailability owing to its poor water solubility. Our aim is to formulate polymeric mixed micelles loaded with FA to overcome its poor solubility and investigate its potential anticancer activity via miRNA-221/TP53INP1 axis-mediated autophagy in colon cancer. A D-optimal design with three factors was used for the optimization of polymeric mixed micelles by studying the efects of each of total Pluronics mixture (mg), Pluronic P123 percentage (%w/w), and drug amount (mg) on both entrapment efciency (EE%) and particle size. The anticancer activity of FA and Tocopheryl polyethylene glycol 1000 succinate (TPGS) mixed micelles formula (O2) was assessed by MTT and fow cytometry. O2 showed an EE% of 99.89%, a particle size of 13.86 nm, and a zeta potential of − 6.02 mv. In-vitro drug release studies showed a notable increase in the release rate of FA from O2, as compared to the free FA. The (IC50) values for FA from O2 and free FA were calculated against diferent cell lines showing a prominent IC50 against Caco-2 (17.1 µg/ml, 191 µg/ml respectively). Flow cytometry showed that FA caused cell cycle arrest at the G2/M phase in Caco-2. RT-PCR showed that O2 signifcantly increased the mRNA expression level of Bax and CASP-3 (4.72 ± 0.17, 3.67 ± 0.14), respectively when compared to free FA (2.59 ± 0.13, 2.14 ± 0.15), while miRNA 221 levels were decreased by the treatment with O2 (0.58 ± 0.02) when compared to free FA treatment (0.79 ± 0.03). The gene expression of TP53INP1 was increased by the treatment with O2 compared to FA at P< 0.0001. FA-loaded TPGS mixed micelles showed promising results for enhancing the anticancer efect of FA against colorectal cancer, probably due to its enhanced solubility.Thus, FA-loaded TPGS mixed micelles could be a potential therapeutic agent for colorectal cancer by targeting miRNA-221/TP53INP1 axis-mediated autophagy.
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    A quality by design approach for the optimization of olmesartan medoxomil-orodispersible lyophilisates: In vitro/in vivo evaluation
    (2022-06) Noshi, Shereen H; Dawoud, Marwa H. S; Ibrahim, Mervat S
    The current study aims to develop orodispersible lyophilisates (ODLs), containing olmesartan medoxomil (OLM), by applying a quality by design approach to ensure product robustness. A thorough risk assessment study was done, where the effects of each of the types of matrix former and superdisintegrant were assessed on the drug content, friability %, cumulative drug released within 15 minutes (Q15%), disintegration time, and wetting time. This was followed by a D-optimal design, for the optimization of the ODL. The optimization study focused on studying the effects of the solubilizer concentration (X1 ) and solubilizer type (X2 ) on the disintegration time (Y1 ) and Q15% (Y2 ). A design space was created with an optimized formula, OLM-ODL, which was prepared and tested to indicate the validity of the design. The optimized formula showed fast drug release with a short disintegration time. Further characterization tests were done on OLM-ODL, as morphological examination, which showed a highly porous nature. Infrared spectroscopy showed no incompatibility. The extent of OLM absorption from the optimized ODL compared to oral OLM suspension from a pharmacokinetic study. The ODL showed an enhancement of the relative bioavailability of the optimized formula of about 345%. Thus, ODLs were successfully developed using a quality by design approach with noticeably improved biopharmaceutical performance.