Lauroyl-gemcitabine-loaded lipid nanocapsule hydrogel for the treatment of glioblastoma

Bastiancich, Chiara; Vanvarenberg, Kévin; Ucakar, Bernard; Pitorre, Marion; Bastiat, Guillaume; Lagarce, Frédéric; Préat, Véronique; Danhier, Fabienne

doi:10.1016/j.jconrel.2016.01.054

Cited by 111 publications

(63 citation statements)

References 68 publications

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“…These lipoprotein carriers can be used to facilitate the delivery and cellular uptake of the LDC in tumor cells with overexpressed lipoprotein receptors. Other reported delivery carriers and formulations for LDCs include mesoporous silica nanoparticles, 133 sesame seed oil injections, 88 lipid nanocapsule hydrogels, 134 and extended release injectable formulations. 89 …”

Section: Delivery Systems For Lipid–drug Conjugatementioning

confidence: 99%

Lipid–Drug Conjugate for Enhancing Drug Delivery

2017

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Lipid–drug conjugates (LDCs) are drug molecules that have been covalently modified with lipids. The conjugation of lipids to drug molecules increases lipophilicity and also changes other properties of drugs. The conjugates demonstrate several advantages including improved oral bioavailability, improved targeting to the lymphatic system, enhanced tumor targeting, and reduced toxicity. Based on the chemical nature of drugs and lipids, various conjugation strategies and chemical linkers can be utilized to synthesize LDCs. Linkers and/or conjugation methods determine how drugs are released from LDCs and are critical for the optimal performance of LDCs. In this review, different lipids used for preparing LDCs and various conjugation strategies are summarized. Although LDCs can be administered without a delivery carrier, most of them are loaded into appropriate delivery systems. The lipid moiety in the conjugates can significantly enhance drug loading into hydrophobic components of delivery carriers and thus generate formulations with high drug loading and superior stability. Different delivery carriers such as emulsions, liposomes, micelles, lipid nanoparticles, and polymer nanoparticles are also discussed in this review.

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Section: Delivery Systems For Lipid–drug Conjugatementioning

confidence: 99%

Lipid–Drug Conjugate for Enhancing Drug Delivery

2017

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“…19 However, addition of NFL solution/suspension above 3 mM in LNC dispersions resulted a viscous and hydrogel like formulation (data not shown), which could be interesting for local application in the cavity after surgical removal of the tumor. 46…”

Section: In Vitro Efficacy On U87mg Cellsmentioning

confidence: 99%

Enhanced and preferential internalization of lipid nanocapsules into human glioblastoma cells: effect of a surface-functionalizing NFL peptide

et al. 2018

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Increasing intracellular drug concentration using nanocarriers can be a potential strategy to improve efficacy against glioblastoma (GBM). Here, the fluorescent-labelled NFL-TBS·40-63 peptide (fluoNFL) concentration on a lipid nanocapsule (LNC) was studied to enhance nanovector internalization into human GBM cells. LNC surface-functionalization with various fluoNFL concentrations was performed by adsorption. LNC size and surface charge altered gradually with increasing peptide concentration, but their complement protein consumption remained low. Desorption of fluoNFL from the LNC surface was found to be slow. Furthermore, it was observed that the rate and extent of LNC internalization in the U87MG human glioblastoma cells were dependent on the surface-functionalizing fluoNFL concentration. In addition, we showed that the uptake of fluoNFL-functionalized LNCs was preferential towards U87MG cells compared to healthy human astrocytes. The fluoNFL-functionalized LNC internalization into the U87MG cells was energy-dependent and occurred possibly by macropinocytosis and clathrin-mediated and caveolin-mediated endocytosis. A new ferrocifen-type molecule (FcTriOH), as a potent anticancer candidate, was then encapsulated in the LNCs and the functionalization improved its in vitro efficacy compared to other tested formulations against U87MG cells. In the preliminary study, on subcutaneous human GBM tumor model in nude mice, a significant reduction of relative tumor volume was observed at one week after the second intravenous injection with FcTriOH-loaded LNCs. These results showed that enhancing NFL peptide concentration on the LNC surface is a promising approach for increased and preferential nanocarrier internalization into human GBM cells, and the FcTriOH-loaded LNCs are a promising therapy approach for GBM.

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“…Oftentimes, combining multiple approaches can improve results, as can be seen when lipidic prodrugs and formulation approaches were taken together . Moreover, the lipidic moiety of the lipid‐drug conjugate may facilitate loading into the delivery systems through hydrophobic interaction, which can improve formulation stability and drug loading, and prevent drug leakage .…”

Section: Discussionmentioning

confidence: 99%

Lipidic prodrug approach for improved oral drug delivery and therapy

Marković

Ben‐Shabat

Keinan

et al. 2018

Medicinal Research Reviews

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In the past, a prodrug design was used as a last option to improve bioavailability through controlling transport, distribution, metabolism, or other mechanisms. Prodrugs are currently used even in early stages of drug development, and a significant percentage of all drugs in the market are prodrugs. The focus of this article is lipidic prodrugs, a strategy whereby a lipid carrier is covalently bound to the drug moiety. The increased lipophilicity of the lipid-drug conjugate can improve the pharmacokinetic profile and provide meaningful advantages: increased absorption across biological barriers, prolonged circulation half-life, selective distribution profile (eg brain penetration), reduced hepatic first-pass metabolism, and overall enhanced bioavailability of the parent drug. Moreover, lipidic prodrugs may join the endogenous lipid trafficking pathways, thereby facilitate drug targeting, either by selective absorption pathway (eg lymphatic transport) or drug release at specific target site(s).The different lipid-drug conjugates (triglyceride-, fatty acids, phospholipid-, and steroid-based prodrugs), the physiological barriers that challenge the absorption of these conjugates, followed by their current utilization and potential clinical benefits are described and analyzed, and future opportunities this approach could provide are discussed.Altogether, lipidic prodrugs represent an exciting approach for improving different aspects of oral drug delivery/therapy and may provide solutions for various unmet needs; the use of this strategy is expected to grow.

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Lauroyl-gemcitabine-loaded lipid nanocapsule hydrogel for the treatment of glioblastoma

Cited by 111 publications

References 68 publications

Lipid–Drug Conjugate for Enhancing Drug Delivery

Lipid–Drug Conjugate for Enhancing Drug Delivery

Enhanced and preferential internalization of lipid nanocapsules into human glioblastoma cells: effect of a surface-functionalizing NFL peptide

Lipidic prodrug approach for improved oral drug delivery and therapy

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