Effect of nanovesicular surface-functionalization via chitosan and/or PEGylation on cytotoxicity of tamoxifen in induced-breast cancer model

Megahed, Mohamed A.; El-Sawy, Hossam S.; Reda, Ahmed; Abd-Allah, Fathy I.; Elyazid, Sherif K. Abu; Lila, Ahmed E.; Ismael, Hatem R.; El-Say, Khalid M.

doi:10.1016/j.lfs.2022.120908

Cited by 13 publications

(23 citation statements)

References 90 publications

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“…The Korsmeyer-Peppas model turned out to be the best model with the highest value of R 2 (Table 4). The degree of release (n) in the Korsmeyer-Peppas equation predicts the release mechanism of the substance, i.e., n < 0.45 corresponds to the Fickian diffusion mechanism [74,78]. The calculated values of n (0.33-0.38) indicate that the release of 2-PAM from chitosomes occurs by diffusion.…”

Section: Discussionmentioning

confidence: 99%

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

et al. 2022

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Chitosan-decorated liposomes were proposed for the first time for the intranasal delivery of acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) to the brain as a therapy for organophosphorus compounds (OPs) poisoning. Firstly, the chitosome composition based on phospholipids, cholesterol, chitosans (Cs) of different molecular weights, and its arginine derivative was developed and optimized. The use of the polymer modification led to an increase in the encapsulation efficiency toward rhodamine B (RhB; ~85%) and 2-PAM (~60%) by 20% compared to conventional liposomes. The formation of monodispersed and stable nanosized particles with a hydrodynamic diameter of up to 130 nm was shown using dynamic light scattering. The addition of the polymers recharged the liposome surface (from −15 mV to +20 mV), which demonstrates the successful deposition of Cs on the vesicles. In vitro spectrophotometric analysis showed a slow release of substrates (RhB and 2-PAM) from the nanocontainers, while the concentration and Cs type did not significantly affect the chitosome permeability. Flow cytometry and fluorescence microscopy qualitatively and quantitatively demonstrated the penetration of the developed chitosomes into normal Chang liver and M-HeLa cervical cancer cells. At the final stage, the ability of the formulated 2-PAM to reactivate brain AChE was assessed in a model of paraoxon-induced poisoning in an in vivo test. Intranasal administration of 2-PAM-containing chitosomes allows it to reach the degree of enzyme reactivation up to 35 ± 4%.

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Section: Discussionmentioning

confidence: 99%

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

et al. 2022

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“…The 3-(4,5-dimethyl thiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay was utilized to evaluate the cytotoxicity of compounds 4k and 4o on normal human liver cells (LO2) and embryonic kidney cells (HEK293). 31 Furthermore, the LO2 and HEK293 were incubated in 96-well plates at a density of 1.5 × 10 4 cells/well at 37 °C and treated with compounds 4k and 4o at concentrations of 10 μg/mL for 24 h, respectively. The absorbance of each well was measured by using a microplate reader at 492 nm, and the assay was repeated three times.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

Antifungal Activity and Mechanism of Camphor Derivatives against Rhizoctonia solani: A Promising Alternative Antifungal Agent for Rice Sheath Blight

Zhang,

Huang,

Duan

et al. 2024

J. Agric. Food Chem.

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Rice sheath blight, caused by the fungus Rhizoctonia solani, poses a significant threat to rice cultivation globally. This study aimed to investigate the potential mechanisms of action of camphor derivatives against R. solani. Compound 4o exhibited superior fungicidal activities in vitro (EC 50 = 6.16 mg/L), and in vivo curative effects (77.5%) at 500 mg/L were significantly (P < 0.01) higher than the positive control validamycin•bacillus (66.1%). Additionally, compound 4o exhibited low cytotoxicity and acute oral toxicity for adult worker honeybees of Apis mellifera L. Mechanistically, compound 4o disrupted mycelial morphology and microstructure, increased cell membrane permeability, and inhibited both PDH and SDH enzyme activities. Molecular docking and molecular dynamics analyses indicated a tight interaction of compound 4o with PDH and SDH active sites. In summary, compound 4o exhibited substantial antifungal efficacy against R. solani, serving as a promising lead compound for further optimization of antifungal agents.

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“…Then, 10 mL of the filtered chitosan solution was added to the previously prepared lipid mixtures’ film (with using enough acetic acid to reach a pH of 3.5-4.5) and used as a hydration medium. In the film synthesis process, PEG 600 or Tween 80 was added to the 100 mg total lipid mix in order to create PEGylated or Tween 80–functionalized-lipidic nanovesicles, respectively (Megahed et al., 2022 ). For drug-loaded nanovesicles, 50 mg of MTC was dissolved in the 10 mL hydration medium and used accordingly.…”

Section: Methodsmentioning

confidence: 99%

“…To learn more about the release mechanism, one can theoretically model the MTC release characteristics from nano-vesicular hybrids. The collected release data were fitted to a variety of kinetic models, including the Higuchi and Korsmeyer-Peppas models, which are frequently used to describe how drugs are released from different types of nanovesicles (El-Say et al., 2015 ; Jana et al., 2014 ; Megahed et al., 2022 ).…”

Section: Methodsmentioning

confidence: 99%

“…The plasma from the collected blood samples was separated by centrifuging at 3000 rpm for 5 min, and the plasma was then permitted to be stored at −80 °C. For the homogenate samples, liver and brain tissue samples that were precisely weighed at 1 gm each were immediately rinsed with normal saline and subjected to tissue homogenization using a probe tissue homogenizer at a pace of 4000 rpm for 3 min in 5 mL of 50 mM Tris-HCl buffer (Megahed et al., 2022 ). The acquired tissue homogenate samples were then placed in freezers and kept at −80 °C until the determination of MTC concentration using the aforementioned HPLC method.…”

Section: Methodsmentioning

confidence: 99%

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PEGylated Tween 80-functionalized chitosan-lipidic nano-vesicular hybrids for heightening nose-to-brain delivery and bioavailability of metoclopramide

Al-Zuhairy¹,

Teaima

Shoman

et al. 2023

Drug Delivery

Self Cite

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A PEGylated Tween 80–functionalized chitosan–lipidic (PEG-T-Chito-Lip) nano-vesicular hybrid was developed for intranasal administration as an alternative delivery route to help improve the poor oral bioavailability of BCS class-III model/antiemetic (metoclopramide hydrochloride; MTC). The influence of varying levels of chitosan, cholesterol, PEG 600, and Tween 80 on the stability/release parameters of the formulated nanovesicles was optimized using Draper-Lin Design. Two optimized formulations (Opti-Max and Opti-Min) with both maximized and minimized MTC-release goals, were predicted, characterized, and proved their vesicular outline via light/electron microscopy, along with the mutual prompt/extended in-vitro release patterns. The dual-optimized MTC–loaded PEG-T-Chito-Lip nanovesicles were loaded in intranasal in-situ gel (ISG) and further underwent in-vivo pharmacokinetics/nose-to-brain delivery valuation on Sprague-Dawley rats. The absorption profiles in plasma (plasma-AUC 0-∞ ) of the intranasal dual-optimized MTC–loaded nano-vesicular ISG formulation in pretreated rats were 2.95-fold and 1.64-fold more than rats pretreated with orally administered MTC and intranasally administered raw MTC-loaded ISG formulation, respectively. Interestingly, the brain-AUC 0-∞ of the intranasal dual-optimized MTC–loaded ISG was 10 and 3 times more than brain-AUC 0-∞ of the MTC-oral tablet and the intranasal raw MTC-loaded ISG, respectively. It was also revealed that the intranasal dual-optimized ISG significantly had the lowest liver-AUC 0-∞ (862.19 ng.g −1 .h −1 ) versus the MTC-oral tablet (5732.17 ng.g −1 .h −1 ) and the intranasal raw MTC-loaded ISG (1799.69 ng.g −1 .h −1 ). The brain/blood ratio profile for the intranasal dual-optimized ISG was significantly enhanced over all other MTC formulations (P < 0.05). Moreover, the 198.55% drug targeting efficiency, 75.26% nose-to-brain direct transport percentage, and 4.06 drug targeting index of the dual-optimized formulation were significantly higher than those of the raw MTC-loaded ISG formulation. The performance of the dual-optimized PEG-T-Chito-Lip nano-vesicular hybrids for intranasal administration evidenced MTC-improved bioavailability, circumvented hepatic metabolism, and enhanced brain targetability, with increased potentiality in heightening the convenience and compliance for patients.

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Effect of nanovesicular surface-functionalization via chitosan and/or PEGylation on cytotoxicity of tamoxifen in induced-breast cancer model

Cited by 13 publications

References 90 publications

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

Therapy of Organophosphate Poisoning via Intranasal Administration of 2-PAM-Loaded Chitosomes

Antifungal Activity and Mechanism of Camphor Derivatives against Rhizoctonia solani: A Promising Alternative Antifungal Agent for Rice Sheath Blight

PEGylated Tween 80-functionalized chitosan-lipidic nano-vesicular hybrids for heightening nose-to-brain delivery and bioavailability of metoclopramide

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