Negative preclinical results with stealth® nanospheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model

Brigger, Irène; Morizet, Jackie; Laudani, Lysiane; Aubert, Geneviève; Appel, M.; Velasco, Valérie; Terrier-Lacombe, Marie-Josée; Desmaële, Didier; d’Angelo, Jean; Couvreur, Patrick; Vassal, Gilles

doi:10.1016/j.jconrel.2004.07.019

Cited by 96 publications

(58 citation statements)

References 20 publications

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“…The large amount of DOX accumulated in brain demonstrated the superior advantage of CS-SA micelles for brain targeting in contrast with the other kinds of nanoparticles whose average drug level in brain was merely 0.1%/g-0.2%/g. [27][28][29][30][31] Transport across BBB for micelles might be related to the high lipophicity increased by SA with a substitute degree of 26%. Moreover, another important contribution to the successful transport of DOX into brain could be bypassing the P-gp effect.…”

Section: Discussionmentioning

confidence: 99%

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Xie¹,

Du²,

Yuan³

et al. 2012

IJN

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Purpose: Therapy for central nervous system disease is mainly restricted by the blood-brain barrier. A drug-delivery system is an effective approach to overcome this barrier. In this research, the potential of polymeric micelles for brain-targeting drug delivery was studied. Methods: Stearic acid-grafted chitosan (CS-SA) was synthesized by hydrophobic modification of chitosan with stearic acid. The physicochemical characteristics of CS-SA micelles were investigated. bEnd.3 cells were chosen as model cells to evaluate the internalization ability and cytotoxicity of CS-SA micelles in vitro. Doxorubicin (DOX), as a model drug, was physically encapsulated in CS-SA micelles. The in vivo brain-targeting ability of CS-SA micelles was qualitatively and quantitatively studied by in vivo imaging and high-performance liquid chromatography analysis, respectively. The therapeutic effect of DOX-loaded micelles in vitro was performed on glioma C6 cells. Results:The critical micelle concentration of CS-SA micelles with 26.9% ± 1.08% amino substitute degree was 65 µg/mL. The diameter and surface potential of synthesized CS-SA micelles in aqueous solution was 22 ± 0.98 nm and 36.4 ± 0.71 mV, respectively. CS-SA micelles presented excellent cellular uptake ability on bEnd.3 cells, the IC 50 of which was 237.6 ± 6.61 µg/mL. DOX-loaded micelles exhibited slow drug-release behavior, with a cumulative release up to 72% within 48 hours in vitro. The cytotoxicity of DOX-loaded CS-SA micelles against C6 was 2.664 ± 0.036 µg/mL, compared with 0.181 ± 0.066 µg/mL of DOX ⋅ HCl. In vivo imaging results indicated that CS-SA was able to transport rapidly across the blood-brain barrier and into the brain. A maximum DOX distribution in brain of 1.01%/g was observed 15 minutes after administration and maintained above 0.45%/g within 1 hour. Meanwhile, free DOX ⋅ HCl was not detected in brain. In other major tissues, DOX-loaded micelles were mainly distributed into lung, liver, and spleen, with a reduction of DOX accumulation in heart. Conclusion: The CS-SA micelles were able to be used as a promising carrier for a braintargeting drug delivery system.

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Section: Discussionmentioning

confidence: 99%

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Xie¹,

Du²,

Yuan³

et al. 2012

IJN

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“…A later study by the same group, which used the same polyacrylate nanoparticulate preparations, interrogated the preclinical efficacy of the free and nanosphere-encapsulated doxorubicin in 9 L gliosarcoma tumor models. 29 The study showed that the doxorubicinloaded nanospheres accumulated more in lungs and spleen and has been attributed to binding of plasma proteins to the charged nanosphere surfaces. Despite this nonspecific accumulation of doxorubicin-loaded nanospheres, the 9 L tumor-bearing animals showed a higher maximum tolerated dose to the nanospheres as compared to the free drug.…”

Section: Synthetic Copolymers For Drug and Sirna Nanoformulationsmentioning

confidence: 99%

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

Ranganathan¹,

Madanmohan²,

Kesavan³

et al. 2012

IJN

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The focus on nanotechnology in cancer treatment and diagnosis has intensified due to the serious side effects caused by anticancer agents as a result of their cytotoxic actions on normal cells. This nonspecific action of chemotherapy has awakened a need for formulations capable of definitive targeting with enhanced tumor-killing. Nanooncology, the application of nanobiotechnology to the management of cancer, is currently the most important area of nanomedicine. Currently several nanomaterial-based drug-delivery systems are in vogue and several others are in various stages of development. Tumor-targeted drug-delivery systems are envisioned as magic bullets for cancer therapy and several groups are working globally for development of robust systems.

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“…Doxorubicin can be delivered across BBB using nanocarrier containing folic acid. Such carrier systems are able to bind with folic acid receptor expressed on the BBB and gain entry into the CNS (Brigger et al, 2004). This type of delivery is suitable even for a highly lipophilic molecule whose size is greater than 400 kDa where the passive diffusion across BBB fails.…”

Section: Focused Ultrasoundmentioning

confidence: 99%

Strategies for drug delivery to the central nervous system by systemic route

et al. 2014

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Context: Delivery of a drug into the central nervous system (CNS) is considered difficult. Most of the drugs discovered over the past decade are biological, which are high in molecular weight and polar in nature. The delivery of such drugs across the blood-brain barrier presents problems.Objective: This review discusses some of the options available to reach the CNS by systemic route. The focus is mainly on the recent developments in systemic delivery of a drug to the CNS. Materials and methods: Databases such as Scopus, Google scholar, Science Direct, SciFinder and online journals were referred for preparing this article including 89 references. Results: There are at least nine strategies that could be adopted to achieve the required drug concentration in the CNS. Conclusion: The recent developments in drug delivery are very promising to deliver biologicals into the CNS.

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Negative preclinical results with stealth® nanospheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model

Cited by 96 publications

References 20 publications

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

Strategies for drug delivery to the central nervous system by systemic route

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Negative preclinical results with stealth® nanospheres-encapsulated Doxorubicin in an orthotopic murine brain tumor model

Cited by 96 publications

References 20 publications

Brain-targeting study of stearic acid&ndash;grafted chitosan micelle drug-delivery system

Brain-targeting study of stearic acid&ndash;grafted chitosan micelle drug-delivery system

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

Strategies for drug delivery to the central nervous system by systemic route

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Product

Resources

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Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system

Brain-targeting study of stearic acid–grafted chitosan micelle drug-delivery system