Pharmacokinetics, biodistribution, and bioavailability of gossypol-loaded Pluronic ® F127 nanoparticles

Wang, Ying; Wang, Ya; Ji, Wang; Wan, Lei; Li, Ké; Wu, Daocheng; Wang, Xiaojuan

doi:10.1016/j.jddst.2018.04.002

Cited by 17 publications

(8 citation statements)

References 31 publications

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“…The pharmacokinetic parameters for free DOX and gossypol obtained in this study were markedly consistent with the literature. [14,40a] Remarkably, compared with the free drugs, DOX–PDA–gossypol NPs significantly improved the blood circulation time of DOX and gossypol in vivo, and, to the best of our knowledge, no nanoparticles can simultaneously make the t 1/2 β of two drugs a few hundred times longer than those of the free drugs (458‐fold for DOX; 228‐fold for gossypol). For example, Han et al designed an inclusion complex (termed as HCPs) loading DOX to form DOX/HCPV5, with t 1/2 β that was 5.1‐fold longer than that of free DOX 41.…”

Section: Resultsmentioning

confidence: 89%

“…We evaluated the in vivo pharmacokinetic behavior of NPs using a mouse model to further investigate whether DOX–PDA–gossypol NPs can improve the long blood circulation. The detection of gossypol in plasma has been developed in our previous work, and that for DOX was also reported . Based on those methods, a new approach was developed to detect the concentrations of DOX and gossypol in plasma at the same time by ultra‐high‐performance liquid chromatography‐electrospray ionization–tandem mass (UHPLC‐ESI–MS/MS) spectrometry.…”

Section: Resultsmentioning

confidence: 99%

“…[14,40a] Remarkably, compared with the free drugs, DOX–PDA–gossypol NPs significantly improved the blood circulation time of DOX and gossypol in vivo, and, to the best of our knowledge, no nanoparticles can simultaneously make the t 1/2 β of two drugs a few hundred times longer than those of the free drugs (458‐fold for DOX; 228‐fold for gossypol). For example, Han et al designed an inclusion complex (termed as HCPs) loading DOX to form DOX/HCPV5, with t 1/2 β that was 5.1‐fold longer than that of free DOX 41. Zou et al developed self‐crosslinkable micellar NPs with DOX (DOX–SCID‐Ms), and the pharmacokinetic studies showed that the t 1/2 β of DOX–SCID‐Ms was 20‐fold longer than that of free DOX .…”

Section: Resultsmentioning

confidence: 99%

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Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

et al. 2018

Adv Funct Materials

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100

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Long blood circulation in vivo remains a challenge to dual-drug-loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop-like dual-drug-loaded nanoparticles (DOX-PDAgossypol NPs) is developed based on the self-assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π-π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long-circulating nanoparticles. The DOX-PDA-gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum-tolerated dose (MTD) of over 60 mg kg -1 , and negligible toxicity. These NPs also exhibit pH-dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458-fold and 258-fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX-PDA-gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.201805582. Recent studies have developed various methods to prolong the blood circulation of NCS. These methods mainly include the surface modification of hydrophilic polymers or nonionic Tumor Therapy

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

et al. 2018

Adv Funct Materials

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100

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“…In some previous studies, the pharmacokinetic behaviors of Gos have been investigated on various species ( Othman and Abou-Donia, 1988 , Jia et al, 2008 , Wang et al, 2018 ). In these studies, at the same dose levels the pharmacokinetic results varied notably among different formulations for Gos and routes of drug administration.…”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that, for the treatment of Gos in the previous studies, the experimental animals were mostly administered with pure Gos powder, and the human patients were treated with plain Gos tablets ( Kumar et al, 1997 , Gu et al, 2000 , Van Poznak et al, 2001 , Yang et al, 2004 , Chang et al, 2011 ). Probably due to the lack of diversity in the dosage form, so far there were very few studies that have focused on the influences of dosage form on the changes (or the extent of fluctuation) in the plasma Gos concentration ( Wang et al, 2018 , Wen et al, 2018 ). Since neither the Gos powders nor the plain Gos tablets had controlled drug release, in our pilot studies considerable fluctuations of plasma drug concentration could be observed after drug administration.…”

Section: Introductionmentioning

confidence: 99%

Gastric floating tablet improves the bioavailability and reduces the hypokalemia effect of gossypol in vivo

Liu

Wang

Shi

et al. 2021

Saudi Pharmaceutical Journal

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Gossypol (Gos) is a natural polyphenolic compound that has shown a number of valuable biological properties such as antifertility, antioxidation, and antitumor activities. However, the clinical application of Gos has been hindered by its notable adverse effects such as hypokalemia, hemolytic anemia, and so on. Using sustained-release dosage form provides a hopeful solution to this problem. In this study, a gastric floating tablet for sustained-release of Gos (Gos-GFT) was developed using polyvinylpyrrolidone, hydroxypropyl methyl cellulose, ethyl cellulose, lactose, sodium bicarbonate, and magnesium stearate. Gos-GFT had an average weight of around 200 mg with a drug content percentage of around 13.66%. The physicochemical properties of Gos-GFT satisfied the pharmacopoeial requirements for tablets. Gos-GFT was able to float in an acidic medium and had a sustained drug release for over 12 h. In vivo studies showed that the relative bioavailability of Gos-GFT, as compared with Gos powders, was larger than that of a non-gastric floating tablet which was a dosage form used for comparison with Gos-GFT. Furthermore, compared with the Gos powders and the non-gastric floating Gos tablets, Gos-GFT could prolong the in vivo action time of Gos, and significantly relieve hypokalemia which is a major adverse effect of Gos. These properties made Gos-GFT a promising Gos preparation that warrants further investigation for more extensive clinical applications of this natural compound.

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Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity

Singh

Kaur

Singh

et al. 2023

Archiv der Pharmazie

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The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp‐EXE‐MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X‐ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT‐PCR and Western blot analysis) in MCF‐7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp‐EXE‐MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp‐EXE‐MMs showed sustained release behavior as compared to EXE‐suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase‐3, p53, and CYP19A1 in MCF‐7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp‐EXE‐MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.

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Pharmacokinetics, biodistribution, and bioavailability of gossypol-loaded Pluronic ® F127 nanoparticles

Cited by 17 publications

References 31 publications

Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol, Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

Gastric floating tablet improves the bioavailability and reduces the hypokalemia effect of gossypol in vivo

Lyophilized mixed micelles of exemestane: A novel paradigm to improve its absorption and anticancer activity

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