Synergistic effect of doxorubicin lauroyl hydrazone derivative delivered by α-tocopherol succinate micelles for the treatment of glioblastoma

Wang, Mingchao; Malfanti, Alessio; Bastiancich, Chiara; Préat, Véronique

doi:10.1016/j.ijpx.2022.100147

Cited by 4 publications

(8 citation statements)

References 53 publications

(74 reference statements)

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“…The synthesis of DOXC 12 was carried out with the method previously reported [32]. Brie y, 100 mg of doxorubicin hydrochloride (Chemieliva, China) and 53.5 mg of dodecanoic hydrazide (ChemCruz, Netherlands) were dissolved in methanol as suspension.…”

Section: Synthesis Of Doxorubicin Lauryl Hydrazone Derivative (Doxc 12 )mentioning

confidence: 99%

“…The product was precipitated by adding diethyl ether (Avantor, USA) and was collected by centrifugation at + 4°C. The nal precipitate was freeze-dried (Labconco, USA) and analyzed by 1 H NMR and HPLC analysis before use as previously reported (data not shown) [32].…”

Section: Synthesis Of Doxorubicin Lauryl Hydrazone Derivative (Doxc 12 )mentioning

confidence: 99%

“…using a Shimadzu Prominence system (Shimadzu, Japan) equipped with a Nucleosil C18 column (Macherey-Nagel, Germany) (150×4.6 mm; particle size 5 µm). As previously reported [32], the mobile phase was composed of 0.1% of formic acid in acetonitrile and 0.1% of formic acid in water (10%, 0 min; 90%, 13-15 min; 10%, 15-20 min, gradient mode). The ow rate was xed at 0.6 ml/min, the detection wavelength was 480 nm and the retention time was 14 min.…”

Section: Quantitative Determinations Of Doxc 12 Content In the Hydrogelmentioning

confidence: 99%

“…DOX is commercialized as water-soluble doxorubicin hydrochloride but for successful incorporation into an LNC-based hydrogel, a DOX prodrug with increased amphiphilicity is required. In previous work, we successfully modi ed DOX by creating a lauroyl hydrazone derivative (DOXC 12 ) [32]. DOXC 12 represents a promising DOX prodrug candidate preserving similar IC 50 as DOX in murine GL261 cells and human U87-MG cells, along with faster cellular uptake due to the lipophilic C 12 lauroyl chain [32].…”

Section: Introductionmentioning

confidence: 99%

“…In previous work, we successfully modi ed DOX by creating a lauroyl hydrazone derivative (DOXC 12 ) [32]. DOXC 12 represents a promising DOX prodrug candidate preserving similar IC 50 as DOX in murine GL261 cells and human U87-MG cells, along with faster cellular uptake due to the lipophilic C 12 lauroyl chain [32]. Additionally, the pHcleavable hydrazone linkers in DOXC 12 can lead to controlled DOX release in an acidic environment.…”

Section: Introductionmentioning

confidence: 99%

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Local delivery of Doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma

Wang

Bergès

Malfanti

et al. 2023

Preprint

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Glioblastoma (GBM) recurrences appear in most cases around the resection cavity borders and arise from residual GBM cells that cannot be removed by surgery. Here, we propose a novel treatment that combines the advantages of nanomedicine and local drug delivery to target these infiltrating GBM cells. We developed an injectable lipid nanocapsules (LNC)-based formulation loaded with lauroyl-doxorubicin prodrug (DOXC12). Firstly, we demonstrated the efficacy of intratumoral administration of DOXC12 in GL261-GBM-bearing mice, which extended mice survival. Then, we formulated an injectable hydrogel by mixing the appropriate amount of prodrug with the lipophilic components of LNC. We optimized the hydrogel by incorporating cytidine-C16 (Cyt-C16) to achieve a mechanical stiffness adapted for an application in the brain post-surgery (DOXC12-LNCCL). DOXC12-LNCCL exhibited high DOXC12 encapsulation efficiency (95%) and a size of approximately 60 nm with sustained drug release in vitro for over 1 month. DOXC12-LNCCL exhibited enhanced cytotoxicity compared to free DOXC12 (IC50 of 49 and 89 nM, respectively) on GL261 GBM cells and prevented growth of GL261 spheroids cultured on organotypic brain slices. In vivo, post-surgical treatment with DOXC12-LNCCL significantly improved the survival of GL261-bearing mice. The combination of this local treatment with the systemic administration of anti-inflammatory drug ibuprofen further delayed the onset of recurrences. In conclusion, our study presents a promising therapeutic approach for the treatment of GBM. By targeting residual GBM cells and reducing the inflammation post-surgery, we present a new strategy to delay the onset of recurrences in the gap period between surgery and standard of care therapy.

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Section: Synthesis Of Doxorubicin Lauryl Hydrazone Derivative (Doxc 12 )mentioning

confidence: 99%

Section: Synthesis Of Doxorubicin Lauryl Hydrazone Derivative (Doxc 12 )mentioning

confidence: 99%

Section: Quantitative Determinations Of Doxc 12 Content In the Hydrogelmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Local delivery of Doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma

Wang

Bergès

Malfanti

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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Nanoparticles Mediated the Diagnosis and Therapy of Glioblastoma: Bypass or Cross the Blood–Brain Barrier

Song

Qian

2023

Small

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Glioblastoma is one of the most aggressive central nervous system malignancies with high morbidity and mortality. Current clinical approaches, including surgical resection, radiotherapy, and chemotherapy, are limited by the difficulty of targeting brain lesions accurately, leading to disease recurrence and fatal outcomes. The lack of effective treatments has prompted researchers to continuously explore novel therapeutic strategies. In recent years, nanomedicine has made remarkable progress and expanded its application in brain drug delivery, providing a new treatment for brain tumors. Against this background, this article reviews the application and progress of nanomedicine delivery systems in brain tumors. In this paper, the mechanism of nanomaterials crossing the blood‐brain barrier is summarized. Furthermore, the specific application of nanotechnology in glioblastoma is discussed in depth.

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Local delivery of doxorubicin prodrug via lipid nanocapsule–based hydrogel for the treatment of glioblastoma

Wang,

Bergès,

Malfanti

et al. 2023

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

Glioblastoma (GBM) recurrences appear in most cases around the resection cavity borders and arise from residual GBM cells that cannot be removed by surgery. Here, we propose a novel treatment that combines the advantages of nanomedicine and local drug delivery to target these infiltrating GBM cells. We developed an injectable lipid nanocapsule (LNC)–based formulation loaded with lauroyl-doxorubicin prodrug (DOXC12). Firstly, we demonstrated the efficacy of intratumoral administration of DOXC12 in GL261 GBM-bearing mice, which extended mouse survival. Then, we formulated an injectable hydrogel by mixing the appropriate amount of prodrug with the lipophilic components of LNC. We optimized the hydrogel by incorporating cytidine-C16 (CytC16) to achieve a mechanical stiffness adapted for an application in the brain post-surgery (DOXC12-LNCCL). DOXC12-LNCCL exhibited high DOXC12 encapsulation efficiency (95%) and a size of approximately 60 nm with sustained drug release for over 1 month in vitro. DOXC12-LNCCL exhibited enhanced cytotoxicity compared to free DOXC12 (IC50 of 349 and 86 nM, respectively) on GL261 GBM cells and prevented the growth of GL261 spheroids cultured on organotypic brain slices. In vivo, post-surgical treatment with DOXC12-LNCCL significantly improved the survival of GL261-bearing mice. The combination of this local treatment with the systemic administration of anti-inflammatory drug ibuprofen further delayed the onset of recurrences. In conclusion, our study presents a promising therapeutic approach for the treatment of GBM. By targeting residual GBM cells and reducing the inflammation post-surgery, we present a new strategy to delay the onset of recurrences in the gap period between surgery and standard of care therapy. Graphical Abstract

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Synergistic effect of doxorubicin lauroyl hydrazone derivative delivered by α-tocopherol succinate micelles for the treatment of glioblastoma

Cited by 4 publications

References 53 publications

Local delivery of Doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma

Local delivery of Doxorubicin prodrug via lipid nanocapsule-based hydrogel for the treatment of glioblastoma

Nanoparticles Mediated the Diagnosis and Therapy of Glioblastoma: Bypass or Cross the Blood–Brain Barrier

Local delivery of doxorubicin prodrug via lipid nanocapsule–based hydrogel for the treatment of glioblastoma

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