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In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting

Acta Pharmaceutica Sinica B 2015年第1期5卷 79-88页

作者： Mohamed Nasr Mohamed K.Ghorab Ahmed Abdelazem Department of Pharmaceutics and Industrial Pharmacy Faculty of Pharmacy Helwan University Department of Pharmaceutical Chemistry Faculty of Pharmacy Helwan University

The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil(5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer.cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly(Po 0.05) increased5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution.However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.

关键词： 5-Fluorouracil Hydrophilic drug cubosomes Liver targeting Hepatotoxicity

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Recent advances in drug delivery applications of cubosomes,hexosomes,and solid lipid nanoparticles

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Acta Pharmaceutica Sinica B 2021年第4期11卷 871-885页

作者： Anan Yaghmur Huiling Mu Department of Pharmacy Faculty of Health and Medical SciencesUniversity of CopenhagenUniversitetsparken 2CopenhagenФ2100Denmark

The use of lipid nanocarriers for drug delivery applications is an active research area,and a great interest has particularly been shown in the past two decades.Among different lipid nanocarriers,ISAsomes(Internally self-assembled somes or particles),including cubosomes and hexosomes,and solid lipid nanoparticles(SLNs)have unique structural features,making them attractive as nanocarriers for drug delivery.In this contribution,we focus exclusively on recent advances in formation and characterization of ISAsomes,mainly cubosomes and hexosomes,and their use as versatile nanocarriers for different drug delivery applications.Additionally,the advantages of SLNs and their application in oral and pulmonary drug delivery are discussed with focus on the biological fates of these lipid nanocarriers in vivo.Despite the demonstrated advantages in in vitro and in vivo evaluations including preclinical studies,further investigations on improved understanding of the interactions of these nanoparticles with biological fuids and tissues of the target sites is necessary for effcient designing of drug nanocarriers and exploring potential clinical applications.

关键词： Biological fate cubosomes Drug delivery Hexosomes Inverse non-lamellar liquid crystalline phases Nano-self-assemblies Solid crystalline phases Solid lipid nanoparticles

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Cubosome nanoparticles for enhanced delivery of mitochondria anticancer drug elesclomol and therapeutic monitoring via sub-cellular NAD(P) H multi-photon fluorescence lifetime imaging

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Nano Research 2019年第5期12卷 991-998页

作者： Ana R.Faria Oscar F.Silvestre Christian Maibohm Ricardo M.R.Adao Bruno F.B.Silva Jana B.Nieder Department of Nanophotonics Ultrafast Bio- and Nanophotonics GroupINL - International Iberian Nanotechnology LaboratoryAv.Mestre Jose Veiga s/n4715-330 BragaPortugal Department of Life Sciences INL-International Iberian Nanotechnology LaboratoryAv.Mestre Jose Veiga s/n4715-330 BragaPortugal

Elesclomol (ELC) is an anticancer drug inducing mitochondria cytotoxicity through reactive oxygen species.Here,for the first time,we encapsulate the poorly water soluble ELC in monoolein-based cubosomes stabilized with Pluronic F127.Cellular uptake and nanocarrier accumulation close to the mitochondria with sub-micrometer distance is identified via three-dimensional (3D) confocal microscopy and edge-to-edge compartment analysis.To monitor the therapeutic effect of the ELC nanocarrier,we apply for the first time,label-free time-lapse multi-photon fluorescence lifetime imaging microscopy (MP-FLIM) to track NAD(P)H cofactors with sub-cellular resolution on live cells exposed to an anticancer nanocarrier.Improved in vitro cytotoxicity is verified when loading the pre-complexed ELC with copper (ELC-Cu).Importantly,for equivalent copper concentration,cubosomes loaded with ELC-Cu show higher cytotoxicity compared to the free drug.The novel nanocarrier shows promising features for systemic ELC-Cu administration,and furthermore we establish the MP-FLIM technique for the assessment of anticancer drug delivery systems.

关键词： cubosomes mitoch on dria reactive oxyge n species elesclomol NAD(P)H fluoresce nee lifetime anticancer therapy

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Efficient Access to Inverse Bicontinuous Mesophases via Polymerization-Induced Cooperative Assembly

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CCS Chemistry 2021年第8期3卷 2214-2225页

作者： Fei Lv Zesheng An Peiyi Wu State Key Laboratory of Supramolecular Structure and Materials College of ChemistryKey Laboratory for Molecular Enzymology and Engineering of Ministry of EducationSchool of Life SciencesJilin UniversityChangchun 130012 State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceLaboratory of Advanced MaterialsFudan UniversityShanghai 200433 State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of ChemistryChemical Engineering and BiotechnologyCenter for Advanced Low-Dimension MaterialsDonghua UniversityShanghai 201620

Polymerization-induced cooperative assembly(PICA)is reported to efficiently access inverse bicontinuous mesophases within particles consisting of amphiphilic block copolymers(BCPs)and solvophobic copolymers.Reversible addition-fragmentation chain transfer(RAFT)dispersion alternating copolymerization of styrene and pentafluorostyrene is conducted in 2%v/v toluene/ethanol by simultaneously using poly(N,N-dimethylacrylamide)(PDMA29)as a macromolecular chain transfer agent(macro-CTA)and small molecule CTA.

关键词： block copolymers bicontinuous mesophases cubosomes hexasomes polymerizationinduced self-assembly polymerization-induced cooperative assembly reversible additionfragmentation chain transfer

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