Liquid chromatography–tandem mass spectrometry evaluation of the pharmacokinetics of a diacid metabolite of norcantharidin loaded in folic acid-targeted liposomes in mice

Liu, Min-Chen; Ma, Xin; Xu, Yong; Peng, Li‐Hua; Han, Min

doi:10.1016/j.jpba.2015.11.017

Cited by 11 publications

(8 citation statements)

References 25 publications

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“…38 The main procedure was as follows: DSPC, cholesterol, DSPE-PEG 2000 , and DSPE-PEG 2000 -FA (2:1:0.11:0.017 molar ratio) were all dissolved in chloroform. To obtain an emulsion, the lipid solution was mixed with phosphate-buffered saline (PBS) containing DM-NCTD and then homogenized in a sonicator (JY92-II; Ningbo Science Biotechnology Co Ltd, Ningbo, PRC).…”

Section: Preparation Of Dm-nctd Liposomesmentioning

confidence: 99%

“…In the current study, we confirmed that the liposome groups exhibited an apparently longer circulation time following intravenous administration to mice (2 mg/kg), while the F r of DM-NCTD increased. 38 We also investigated the tumor-targeting efficiency, antineoplastic activity, and preliminary toxicity evaluation at the moderate The average sizes of the DM-NCTD/PEG liposomes and DM-NCTD/FA-PEG liposomes were approximately 203 and 205 nm, respectively; these sizes are preferable for tumor accumulation via the EPR effect. [24][25][26] Moreover, the zeta potential (5.9 and 6.9 mV, respectively) analyses demonstrated that both types of drug-loaded liposome exhibited approximately neutral surface charge, which would minimize undesirable nonspecific protein adsorption (Table 1).…”

Section: Dose Of Dm-nctdmentioning

confidence: 99%

“…In a previous study, we confirmed the prolonged circulation characteristics of related parameters and increased the relative bioavailability (F r ) of DM-NCTD liposomes (compared with DM-NCTD as the reference formulation) in Kunming mice at a moderate dose (2 mg/kg) converted from the clinical dosage used in the People's Republic of China (PRC). 9,38 Although the results indicated that a liposomal drug-delivery system could have the potential to overcome the shortcomings of DM-NCTD by improving F r and increasing therapeutic efficacy, further in vitro and in vivo studies on tumor-targeted FR-mediated DM-NCTD liposome therapy are still needed to confirm these results. Therefore, the aim of this study was to develop tumor-targeted delivery for DM-NCTD and confirm its targeting characteristics at a moderate dose.…”

Section: Introductionmentioning

confidence: 99%

“…7,38 However, investigations into the stability of DM-NCTD liposomes are essential, because liposomal stability is a prerequisite for achieving long circulation time and tumor-targeted delivery, which is strongly influenced by the hydrophilic stealth layer, zeta potential, lipid composition, particle size, and distribution. 46 In the current study, DSPE-PEG 2000 was used as the definitive functional phospholipid in the liposomal formulation to maintain a long circulation time and specific stability.…”

mentioning

confidence: 99%

“…In vivo biodistribution in h22 tumor-bearing mice FA-modified liposomes were used as biocompatible carriers to reduce the potential toxicity of DM-NCTD, prolong its retention time, 38 and increase its tumor-targeting ability. [31][32][33][34] In the current study, the tissue-and tumor-targeting characteristics of DM-NCTD and DM-NCTD liposomes were evaluated through biodistribution.…”

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confidence: 99%

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Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo

Liu¹,

Liu²,

Wang³

et al. 2016

IJN

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The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification ( P <0.01). We used liquid chromatography–mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments ( P <0.01). Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes ( P <0.01), and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues of model mice or the liver tissue of normal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy.

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Section: Preparation Of Dm-nctd Liposomesmentioning

confidence: 99%