Pharmaceutical polymers and P-glycoprotein: Current trends and possible outcomes in drug delivery

Attia, Mohamed S.; Elsebay, Mohamed T.; Yahya, Galal; Chopra, Hitesh; Marzouk, Mohamed; Yehya, Ahmed; Abdelkhalek, Ahmed S.

doi:10.1016/j.mtcomm.2023.105318

Cited by 11 publications

(5 citation statements)

References 169 publications

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“…The results suggest that non-Pgp substrates exhibit improved persistence in their cells. The role of P-gp in drug transport is essential for pharmacology and drug development, as it can influence the bioavailability and efficacy of various medications (Karthika et al 2022 ; Rachmale et al 2022 ; Attia et al 2023 ). In order to maintain consistent plasma concentrations and enhance the absorption of the tested compounds, it was expected that these substances would exhibit inhibitory actions on all five cytochrome P450 enzyme classes, namely CYP2C9, CYP2C19, CYP3A4, CYP1A2, and CYP2D6.…”

Section: Resultsmentioning

confidence: 99%

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Shahzadi,

Yousaf,

Anjum

et al. 2024

Bioresour. Bioprocess.

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Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein–protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, −7.1, −9.0 and −8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Shahzadi,

Yousaf,

Anjum

et al. 2024

Bioresour. Bioprocess.

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“…We speculate that this intensified permeation may be attributed to alginate, which has been shown to act as an efflux protein (P-gp) inhibitor. 41,42 Since the particle size of the preparation is at the micron level, it is unable to facilitate insulin permeation through the basolateral cells to the same extent as the prevalent insulin-loaded nanoparticles. However, Ins/Ur/MgO@SA microspheres can protect the structure of insulin from destruction before it is absorbed into the blood and increase the chance of insulin absorption through longterm retention in the GI tract.…”

Section: Biomaterials Science Papermentioning

confidence: 99%

Urease catalyzed high-density sodium alginate microspheres enable high oral bioavailability of macromolecular drugs

Jiang,

Mi,

et al. 2024

Biomater. Sci.

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“…Formulations, pharmaceutical excipients, and tailored compounds are all examples of P-gp inhibitors. As a result of their beneficial effect on P-gp, functionalized polymers such as chitosan, soluplus ® , poloxamers, polyethylene glycols, dendrimers, anionic gums, sodium alginate, and others could be used as drug delivery tools [ 76 ]. Due to the importance of P-glycoprotein (P-gp) in the active transport of different substrates with different structures outside of cells, intestinal permeability is reduced, and bioavailability is decreased after oral administration.…”

Section: Applicability Of Chitosan-oriented Multifarious Deliverymentioning

confidence: 99%

Chitosan in Oral Drug Delivery Formulations: A Review

Sangnim,

Dheer,

Jangra

et al. 2023

Pharmaceutics

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Nanoformulations have become increasingly useful as drug delivery technologies in recent decades. As therapeutics, oral administration is the most common delivery method, although it is not always the most effective route because of challenges with swallowing, gastrointestinal discomfort, low solubility, and poor absorption. One of the most significant barriers that medications must overcome to exert a therapeutic effect is the impact of the first hepatic transit. Studies have shown that controlled-release systems using nanoparticles composed of biodegradable natural polymers significantly improve oral administration, which is why these materials have attracted significant attention. Chitosan possesses a wide variety of properties and functions in the pharmaceutical as well as healthcare industries. Drug encapsulation and transport within the body are two of its most important features. Moreover, chitosan can enhance drug efficacy by facilitating drug interaction with target cells. Based on its physicochemical properties, chitosan can potentially be synthesized into nanoparticles, and this review summarizes recent advances and applications of orally delivered chitosan nanoparticle interventions.

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Pharmaceutical polymers and P-glycoprotein: Current trends and possible outcomes in drug delivery

Cited by 11 publications

References 169 publications

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Urease catalyzed high-density sodium alginate microspheres enable high oral bioavailability of macromolecular drugs

Chitosan in Oral Drug Delivery Formulations: A Review

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