Browsing by Author "Sweed, Nabila M"

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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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    Optimization of nanovesicular carriers of a poorly soluble drug using factorial design methodology and artificial neural network by applying quality by design approach
    (Taylor and Francis Ltd., 09/12/2021) Dawoud, Marwa H.S; Fayez, Ahmed M; Mohamed, Reem A; Sweed, Nabila M
    The aim of the current work is to utilize quality by design (QbD) approach to develop and optimize nanovesicular carriers of a hydrophobic drug. Rosuvastatin calcium was used as a model drug, which suffers poor bioavailability. Several tools were used in the risk assessment study as Ishikawa diagrams. The critical process parameters (CPP) were found to be the particle size, polydispersity index, zeta potential and entrapment efficiency. Factorial design was used in risk analysis, which was complemented with artificial neural network (ANN); to assure its accuracy. A design space was established, with an optimized nanostructured lipid carrier formula containing 3.2% total lipid content, 0.139% surfactant and 0.1197 mg % drug. The optimized formula showed a sustained drug release up to 72 hours. It successfully lowered each of the total cholesterol, low density lipoprotein and triglycerides and elevated the high-density lipoprotein levels, as compared to the standard drug. Thus, the concurrent use of the factorial design with ANN using QbD approach permitted the exploration of the experimental regions for a successful nanovesicular carrier formulation, and could be used as a reference for many nanostructured drug delivery studies during their pharmaceutical development and product manufacturing.
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    The pulmonary protective potential of vanillic acid-loaded TPGS-liposomes: modulation of miR-217/MAPK/NF-κb signalling pathway
    (Taylor and Francis Ltd, 2024-04) Sweed, Nabila M; Zaafan, Mai A; El-Bishbishy, Mahitab H; Dawoud, Marwa H.S
    The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA’s poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of −32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.