Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38

Bala, Vaskor; Rao, Shasha; Boyd, Ben J.; Prestidge, Clive A.

doi:10.1016/j.jconrel.2013.07.022

Cited by 172 publications

(134 citation statements)

References 94 publications

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“…They exert their activity by binding to the complex formed by DNA topoisomerase I and DNA. This results in a stable ternary complex, thus preventing DNA re-ligation and causing DNA damage and cell death 35 . Despite being potent chemotherapeutics, the poor solubility of CPT and SN38 in most pharmaceutically accepted solvents limits their clinical application.…”

Section: Discussionmentioning

confidence: 99%

Targeted drug delivery using genetically engineered diatom biosilica

et al. 2015

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The ability to selectively kill cancerous cell populations while leaving healthy cells unaffected is a key goal in anticancer therapeutics. The use of nanoporous silica-based materials as drug-delivery vehicles has recently proven successful, yet production of these materials requires costly and toxic chemicals. Here we use diatom microalgae-derived nanoporous biosilica to deliver chemotherapeutic drugs to cancer cells. The diatom Thalassiosira pseudonana is genetically engineered to display an IgG-binding domain of protein G on the biosilica surface, enabling attachment of cell-targeting antibodies. Neuroblastoma and B-lymphoma cells are selectively targeted and killed by biosilica displaying specific antibodies sorbed with drug-loaded nanoparticles. Treatment with the same biosilica leads to tumour growth regression in a subcutaneous mouse xenograft model of neuroblastoma. These data indicate that genetically engineered biosilica frustules may be used as versatile 'backpacks' for the targeted delivery of poorly water-soluble anticancer drugs to tumour sites.

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Section: Discussionmentioning

confidence: 99%

Targeted drug delivery using genetically engineered diatom biosilica

et al. 2015

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“…First, the lactone ring of SN-38 was prone to hydrolysis at pH 7.4, 41 and the stability of the lactone ring in SN-38/ NCs might be enhanced significantly compared to the solution. 28,42 Second, SN-38 is a P-gp substrate.…”

Section: In Vitro Cytotoxicity Studiesmentioning

confidence: 99%

“…41 However, the drug molecules in SN-38 nanocrystals were slowly released after injection and the solid particles might restrict the hydrolysis of the active lactone ring, which meant that there was more active drug to kill the tumor cells. Moreover, the circulation of SN-38 in the blood was prolonged by the formulation of nanocrystals, which improved the bioavailability of SN-38 and was conducive to inhibit the tumor growth.…”

Section: Pharmacokinetic Evaluationmentioning

confidence: 99%

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Chen¹,

Li²,

Zhang³

et al. 2017

IJN

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7-Ethyl-10-hydroxycamptothecin (SN-38) is a potent broad-spectrum antitumor drug derived from irinotecan hydrochloride (CPT-11). Due to its poor solubility and instability of the active lactone ring, its clinical use is significantly limited. As one of the most promising formulations for poorly water-soluble drugs, nanocrystals have attracted increasing attention. In order to solve these problems and evaluate the antitumor effect of SN-38 in vitro and in vivo, two nanocrystals with markedly different particle sizes were prepared. Dynamic light scattering and transmission electron microscopy were used to investigate the two nanocrystals. The particle sizes of SN-38 nanocrystals A (SN-38/NCs-A) and SN-38 nanocrystals B (SN-38/NCs-B) were 229.5±1.99 and 799.2±14.44 nm, respectively. X-ray powder diffraction analysis showed that the crystalline state of SN-38 did not change in the size reduction process. An accelerated dissolution velocity of SN-38 was achieved by nanocrystals, and release rate of SN-38/NCs-A was significantly faster than that of SN-38/NCs-B. Cellular uptake, cellular cytotoxicity, pharmacokinetics, animal antitumor efficacy, and tissue distribution were subsequently examined. As a result, enhanced intracellular accumulation in HT1080 cells and cytotoxicity on different tumor cells were observed for SN-38/NCs-A compared to that for SN-38/NCs-B and solution. Besides, compared to the SN-38 solution, SN-38/NCs-A had a higher bioavailability after intravenous injection; while the bioavailability of SN-38/NCs-B was even lower than that of the SN-38 solution. SN-38/NCs-A exhibited a significant inhibition of tumor growth compared to SN-38 solution and SN-38/NCs-B in vivo. The antitumor effect of SN-38/NCs-B was stronger than SN-38 solution. The tissue distribution study in tumor-bearing mice showed that nanocrystals could markedly improve the drug accumulation in tumor tissue by the enhanced permeability and retention effect compared to SN-38 solution, and the amount of SN-38 in tumors of SN-38/NCs-A group was much more than that of SN-38/NCs-B group. In conclusion, nanocrystals dramatically enhanced the anticancer efficacy of SN-38 in vitro and in vivo, and the particle size had a significant influence on the dissolution behavior, pharmacokinetic properties, and tumor inhibition of nanocrystals.

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“…For example, liposomes, carbon nanotubes, dendrimers, and micelles have been used as carriers for SN38, doxorubicin, paclitaxel, and cisplatin to improve drug concentrations in tumors and reduce adverse effects. [2][3][4][5] Another advantage of using nanomaterials as drug carriers is the enhanced solubility of chemotherapeutic drugs. Many of these agents have poor aqueous solubility, leading to low bioavailability.…”

Section: Introductionmentioning

confidence: 99%

Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery

Liu¹,

Liu²,

Xu³

et al. 2013

IJN

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The poor aqueous solubility and low bioavailability of curcumin restrict its clinical application for cancer treatment. In this study, a novel tumor-targeting nanofiber carrier was developed to improve the solubility and tumor-targeting ability of curcumin using a self-assembled Nap-GFFYG-RGD peptide. The morphologies of the peptide nanofiber and the curcumin-encapsulated nanofiber were visualized by transmission electron microscopy. The tumor-targeting activity of the curcumin-encapsulated Nap-GFFYG-RGD peptide nanofiber (f-RGD-Cur) was studied in vitro and in vivo, using Nap-GFFYG-RGE peptide nanofiber (f-RGE-Cur) as the control. Curcumin was encapsulated into the peptide nanofiber, which had a diameter of approximately 10–20 nm. Curcumin showed sustained-release behavior from the nanofibers in vitro. f-RGD-Cur showed much higher cellular uptake in αvβ3 integrin-positive HepG2 liver carcinoma cells than did non-targeted f-RGE-Cur, thereby leading to significantly higher cytotoxicity. Ex vivo studies further demonstrated that curcumin could accumulate markedly in mouse tumors after administration of f-RGD-Cur via the tail vein. These results indicate that Nap-GFFYG-RGD peptide self-assembled nanofibers are a promising hydrophobic drug delivery system for targeted treatment of cancer.

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Prodrug and nanomedicine approaches for the delivery of the camptothecin analogue SN38

Cited by 172 publications

References 94 publications

Targeted drug delivery using genetically engineered diatom biosilica

Targeted drug delivery using genetically engineered diatom biosilica

In vitro and in vivo evaluation of SN-38 nanocrystals with different particle sizes

Novel tumor-targeting, self-assembling peptide nanofiber as a carrier for effective curcumin delivery

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