Lipid nanoparticles loaded with 7-ethyl-10-hydroxycamptothecin-phospholipid complex:<i>in vitro</i>and<i>in vivo</i>studies

Liu, Huan; Lü, Hua; Liao, Longfei; Zhang, Xuanmiao; Gong, Tao; Zhang, Zhirong

doi:10.3109/10717544.2014.895069

Cited by 19 publications

(9 citation statements)

References 35 publications

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“…Therefore, the direct administration of SN38 might be of benefit for cancer patients. However, the poor solubility in aqueous and other pharmaceutical solvents (including ethanol, cremophor and polysorbate 80) limits its application (25), which has been proven previously by our group and others (26,27). Generally, CPT derivatives are expected to have improved solubility and stability.…”

Section: Discussionmentioning

confidence: 91%

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06

Zhao

et al. 2017

Oncol Rep

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Camptothecin (CPT) is a cytotoxic quinoline alkaloid that is used clinically as an anticancer drug. However, the clinical application of CPT is limited due to its low solubility as well as serious and unfathomable side-effects. In the present study, we created a novel 10-hydroxy CPT prodrug, ZBH-ZM‑06. Its cellular cytotoxic activity was analyzed in terms of cellular viability, acetylcholinesterase (AchE) inhibition, DNA relaxation, cellular cycling and apoptosis properties. Our results showed that the AchE inhibition rate of 10 µmol/l ZBH-ZM-06 was 12.5%, compared to 96.5% for carbonyl-oxycamptothecin (CPT-11). In a chemical stability assay, only 4.9% of ZBH-ZM-06 remained after 4 h at pH 7.4. In addition, 10 µmol/l ZBH-ZM-06 significantly inhibited the tumor cell viability of nine tumor cell lines, compared to CPT-11 and the CPT active ingredient, 7-ethyl-10-hydroxy-camptothecin (SN38) (p<0.01-0.05). In the apoptosis assay, ZBH-ZM-06 increased the ratio of annexin V+/propidium iodide (PI)-/+ cells by flow cytometric analysis (p<0.05). Moreover, ZBH-ZM-06 activated caspase-3 and poly(ADP-ribose)polymerase (PARP) expression by immunoblotting. Furthermore, ZBH-ZM-06 induced a greater G2/M phase arrest ratio, compared to CPT-11 and SN38. These results indicated that ZBH-ZM-06 had higher antitumor activity than CPT-11 and SN38, which was shown by its: i) release of the effective ingredient; ii) growth inhibition of a broad spectrum of tumor cells; iii) inhibition of DNA topoisomerase (Topo-1); and iv) promotion of apoptosis through an intrinsic signaling pathway. Thus, ZBH-ZM-06 may be applied in the preclinic study for cancer treatment.

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Section: Discussionmentioning

confidence: 91%

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06

Zhao

et al. 2017

Oncol Rep

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“…In total, there were 376 data sets from 200 NP tumor delivery studies in tumor-bearing mice that were included for PBPK simulations and analyses (Table S1). − ,,,− ,− ,,,,,− …”

Section: Methodsmentioning

confidence: 99%

Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach

et al. 2020

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Numerous studies have engineered nanoparticles with different physicochemical properties to enhance the delivery efficiency to solid tumors, yet the mean and median delivery efficiencies are only 1.48% and 0.70% of the injected dose (%ID), respectively, according to a study using a nonphysiologically based modeling approach based on published data from 2005 to 2015. In this study, we used physiologically based pharmacokinetic (PBPK) models to analyze 376 data sets covering a wide range of nanomedicines published from 2005 to 2018 and found mean and median delivery efficiencies at the last sampling time point of 2.23% and 0.76%ID, respectively. Also, the mean and median delivery efficiencies were 2.24% and 0.76%ID at 24 h and were decreased to 1.23% and 0.35%ID at 168 h, respectively, after intravenous administration. While these delivery efficiencies appear to be higher than previous findings, they are still quite low and represent a critical barrier in the clinical translation of nanomedicines. We explored the potential causes of this poor delivery efficiency using the more mechanistic PBPK perspective applied to a subset of gold nanoparticles and found that low delivery efficiency was associated with low distribution and permeability coefficients at the tumor site (P < 0.01). We also demonstrate how PBPK modeling and simulation can be used as an effective tool to investigate tumor delivery efficiency of nanomedicines.

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“…These approaches showed superiority over conventionally delivered irinotecan, but most were designed primarily to address the poor solubility of SN38 and did not take full advantage of the EPR effect. Others have used lipid or chitosan nanocapsules for oral or parental administration (33–35). Finally, another study developed polymeric NPs encapsulating SN38 using poly lactic-co-glycolic acid (36).…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle delivery of an SN38 conjugate is more effective than irinotecan in a mouse model of neuroblastoma

et al. 2015

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Neuroblastoma (NB) is the most common and deadly solid tumor in children. The majority of NB patients have advanced stage disease with poor prognosis, so more effective, less toxic therapy is needed. We developed a novel nanocarrier-based strategy for tumor-targeted delivery of a prodrug of SN38, the active metabolite of irinotecan. We formulated ultrasmall-sized ( < 100 nm) biodegradable poly(lactide)-poly(ethylene glycol) based nanoparticles (NPs) containing SN38 conjugated to tocopherol succinate (SN38-TS). Alternative dosing schedules of SN38-TS NPs were compared to irinotecan. Comparison of SN38-TS NPs (2 doses) with irinotecan (20 doses) showed equivalent efficacy but no cures. Comparison of SN38-TS NPs (8, 8, and 16 doses, respectively) to irinotecan (40 doses) showed that all SN38-TS NP regimens were far superior to irinotecan, and “cures” were obtained in all NP arms. SN38-TS NP delivery resulted in 200x the amount of SN38 in NB tumors at 4 hr post-treatment, compared to SN38 detected for the irinotecan arm; no toxicity was seen with NPs. We conclude that this SN38-TS NP formulation improved delivery, retention, and efficacy, without causing systemic toxicity.

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Lipid nanoparticles loaded with 7-ethyl-10-hydroxycamptothecin-phospholipid complex:in vitroandin vivostudies

Cited by 19 publications

References 35 publications

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06

Antitumor potential of a novel camptothecin derivative, ZBH-ZM-06

Meta-Analysis of Nanoparticle Delivery to Tumors Using a Physiologically Based Pharmacokinetic Modeling and Simulation Approach

Nanoparticle delivery of an SN38 conjugate is more effective than irinotecan in a mouse model of neuroblastoma

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