Cremophor-free intravenous self-microemulsions for teniposide: Safety, antitumor activity in vitro and in vivo

He, Suna; Cui, Zheng; Wang, Xueqing; Zhang, Hua; Dai, Wenbing; Zhang, Qiang

doi:10.1016/j.ijpharm.2015.08.005

Cited by 7 publications

(2 citation statements)

References 25 publications

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“…Emulsion-based formulations were tested, but obtaining stable and micrometric sized emulsions required high energy processes and high levels of surfactants with potential toxicity. [ 32 ] Thus, we considered a nanoencapsulation strategy and the formulation of EAPB0503-loaded LNC as injectable delivery systems. Different hydrophobic anticancer drugs have been encapsulated by this process.…”

Section: Discussionmentioning

confidence: 99%

Lipid nanocapsules formulation and cellular activities evaluation of a promising anticancer agent: EAPB0503

Chouchou

Aubert-Pouëssel

Dorandeu

et al. 2017

Int J Pharma Investig

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Objective:EAPB0503, lead compound of imiqualines, presented high antitumor activities but also a very low water solubility which was critical for further preclinical studies. To apply to EAPB0503, a robust and safe lipid formulation already used for poor soluble anticancer agents for injectable administration at a concentration higher than 1 mg/mL.Materials and Methods:Physicochemical properties of EAPB0503 were determined to consider an adapted formulation. In a second time, lipid nanocapsules (LNC) formulations based on the phase-inversion process were developed for EAPB0503 encapsulation. Then, EAPB0503 loaded-LNC were tested in vitro on different cell lines and compared to standard EAPB0503 solutions.Results:Optimized EAPB0503 LNC displayed an average size of 111.7 ± 0.9 nm and a low polydispersity index of 0.059 ± 0.002. The obtained loading efficiency was higher than 96% with a drug loading of 1.7 mg/mL. A stability study showed stability during 4 weeks stored at 25°C. In vitro results highlighted similar efficiencies between LNC and standard EAPB0503 solutions prepared in dimethyl sulfoxide.Conclusion:In view of results obtained for loading efficiency and drug loading, the use of a LNC formulation is very interesting to permit the solubilization of a lipophilic drug and to improve its bioavailability. Preliminary tested pharmaceutical formulation applied to EAPB0503 significantly improved its water solubility and will be soon considered for future preclinical in vivo studies.

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Section: Discussionmentioning

confidence: 99%

Lipid nanocapsules formulation and cellular activities evaluation of a promising anticancer agent: EAPB0503

Chouchou

Aubert-Pouëssel

Dorandeu

et al. 2017

Int J Pharma Investig

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“…When tumor volume reached about 300 mm 3 , MCF-7 tumor bearing mice were randomly assigned to groups for live imaging studies. All procedures were approved by the Institutional Animal Care and Use Committee at Peking University Health Science Center and were in accordance with international guidelines on the ethical use of animals [31][32] .…”

Section: % Ldh Release=mentioning

confidence: 99%

Visualizing in vitro-in vivo correlation of miktoarm copolymer nanomicelles in cancer cellular uptake and trafficking

Cui

Zhang

et al. 2019

Preprint

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In this study, a clear correlation between the in vitro and in vivo cellular uptake and trafficking was discovered by delivering miktoarm copolymer nanomicelles (MCNs) to cancer cells and tumor tissues. To monitor this process, two different FRET pairs, DiO and DiI, DiD and DiR, were loaded into MCNs to monitor the Förster resonance energy transfer (FRET) efficiency. The change in FRET efficiency in vitro and in vivo demonstrated a similar sequence of events for the transport of MCNs: hyperbranched block PCL inserted into cytomembrane, while the loaded hydrophobic fluorescence probes were released and followed by time-dependent intracellular clustering within endocytic vesicles. Additionally, uptake of loaded fluorescence probes with successively increasing ratios of copolymers suggested that with the increase of mass ratio of copolymer to fluorescence probes, cellular uptake of probes significantly decreased. This result was also consistent with the uptake behavior in cancer tissues. Collectively, the interaction between MCNs and cellular membrane dictated the uptake and trafficking of core-loaded hydrophobic probes. This concept paves a new way to analyze in vitro-in vivo correlation of other nanocarriers for endocytosis mechanism studies as well as further novel copolymers design in biomedical applications. Keywords: miktoarm copolymers• nanomicelles• cellular uptake• intracellular trafficking• FRET• in vitro-in vivo correlationAdvances in nanotechnology have fostered to construct a diversity of nanomaterials with the ability to encapsulate and transport therapeutic or diagnostic agents 1-3 . Among these nanoscale delivery vehicles, polymeric micelles attracted the most attention in diverse biomedical fields as drug delivery vehicles 4-5 , contrast agents carriers 6-7 and diagnostic devices [8][9] . The advantages of polymeric micelles used as drug delivery vectors include improving the solubility of poorly water soluble drugs with the amphiphilic structures 10 , stabilizing and protecting drugs that are sensitive to the surrounding environment 11 , reducing nonspecific uptake by the reticuloendothelial system (RES) 12 and achieving the passive targeting delivery in solid tumors [13][14] . The conventional micelle drug delivery systems are mainly based on linear amphiphilic copolymers. However, linear amphiphilic copolymer micelles will dissemble in vivo when the concentration of the copolymer is diluted by the bloodstream to fall below the critical In this case, the similar chemical structures of DiO, DiI, DiD and DiR could aid us to construct dye-loaded MCNs with similar release behavior in order to discover the in vitro -in vivo correlation. (3) The FRET pair DiO and DiI, with DiO as donor and DiI as acceptor, was used to monitor FRET efficiency in vitro; while the second FRET pair DiD and DiR, with DiD as donor and DiR as acceptor was used to detect the change of FRET efficiency in vivo.

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Self-microemulsifying delivery system for improving bioavailability of water insoluble drugs

Yan

Guo

et al. 2020

J Nanopart Res

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Cremophor-free intravenous self-microemulsions for teniposide: Safety, antitumor activity in vitro and in vivo

Cited by 7 publications

References 25 publications

Lipid nanocapsules formulation and cellular activities evaluation of a promising anticancer agent: EAPB0503

Lipid nanocapsules formulation and cellular activities evaluation of a promising anticancer agent: EAPB0503

Visualizing in vitro-in vivo correlation of miktoarm copolymer nanomicelles in cancer cellular uptake and trafficking

Self-microemulsifying delivery system for improving bioavailability of water insoluble drugs

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