Human placental cell and tissue uptake of doxorubicin and its liposomal formulations

Soininen, Suvi K.; Repo, Jenni; Karttunen, Vesa; Auriola, Seppo; Vähäkangas, Kirsi; Ruponen, Marika

doi:10.1016/j.toxlet.2015.09.011

Cited by 34 publications

(29 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that although DOX showed nanomolar IC 50 values under these conditions, DOX/Lip showed micromolar IC 50 values. This likely reflects the fact that DOX is amphipathic, facilitating its internalization across the cell membrane, 54 whereas the PEG side chains on the surface of DOX/Lip inhibit internalization. 55 In fact, PEGylation is often desirable because it prevents the liposomes from interacting with components that could clear it from the circulation, including the RES.…”

Section: Antitumor Efficacy Of Liposomal Dox When Combined With Liposmentioning

confidence: 99%

Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin

et al. 2016

View full text Add to dashboard Cite

He (2016) Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin, Autophagy, 12:6, 949-962, DOI: 10.1080/15548627.2016 HCQ/Lip-TR was efficiently internalized as a result of its ability to bind ITGAV-ITGB3/integrin a v b 3 receptors highly expressed on the tumor cell surface and to undergo charge reversal from anionic at pH 7.4 to cationic at pH 6.5. Studies in vitro at pH 6.5 showed that the intracellular HCQ concentration was 35.68-fold higher, and lysosomal HCQ concentration 32.22-fold higher, after treating cultures with HCQ/Lip-TR than after treating them with free HCQ. The corresponding enhancements observed in mice bearing B16F10 tumors were 15.16-fold within tumor cells and 14.10-fold within lysosomes. HCQ/Lip-TR was associated with milder anemia and milder myosuppressive reductions in white blood cell and platelet counts than free HCQ, as well as less accumulation in the small intestine, which may reduce risk of intestinal side effects. In addition, co-delivering HCQ/Lip-TR with either free doxorubicin (DOX) or liposomal DOX improved the ability of DOX to inhibit tumor growth. Biochemical, electron microscopy and immunofluorescence experiments confirmed that HCQ/Lip-TR blocked autophagic flux in tumor cells. Our results suggest that loading HCQ into Lip-TR liposomes may increase the effective concentration of the inhibitor in tumor cells, allowing less toxic doses to be used.

show abstract

Section: Antitumor Efficacy Of Liposomal Dox When Combined With Liposmentioning

confidence: 99%

Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Moreover, these studies also suggest that distribution volume and elimination (half-life) of doxorubicin are not statistically different in pregnant than in non-pregnant women [22,[27][28][29]. Placental capacity to transfer doxorubicin or pegylated liposomal doxorubicin from maternal blood to the fetal circulation was studied ex vivo with the human placental perfusion model [34]. This study showed a rapid decrease in doxorubicin concentration, with 30% doxorubicin remaining in the maternal circulation after 4 h, and 12% doxorubicin in the fetal circulation.…”

Section: Discussionmentioning

confidence: 97%

Maternal ABVD chemotherapy for Hodgkin lymphoma in a dichorionic diamniotic pregnancy: a case report

Cotteret

Pham

Marçais

et al. 2020

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

Background: Hodgkin lymphoma (HL) is the most common hematological malignancy during pregnancy. The firstline treatment for HL in pregnancy is the standard ABVD regimen without any drug and/or dose adjustment. However, data on chemotherapy during twin pregnancies are sparse, and a better understanding of the mechanisms involved in exposure to and the toxic effects of anticancer drugs in the fetuses is needed. Case presentation: A 41-year-old dichorionic diamniotic pregnant patient was given ABVD treatment for HL at a gestational age of 28 weeks and 3 days. The patient received 2 cycles of chemotherapy with a 15-day therapeutic window including an actual 25 mg/m 2 dose of doxorubicin per cycle. Unlike the female twin, the male twin presented four days after birth a left cardiac dysfunction. Doxorubicin cardiotoxicity in the male newborn was also supported by high blood levels of troponin. At one month of age, echocardiography findings were normal. We investigated literature data on physiological aspects of pregnancy that may influence doxorubicin pharmacokinetics, and pharmacodynamic and pharmacokinetic data on the use of doxorubicin in pregnancy. We detailed the role of the transporters in doxorubicin placenta distribution, and tried to understand why only one fetus was affected. Conclusions: Fetal safety depends at least on maternal doxorubicin pharmacokinetics.Because of drug interactions (i.e. drug metabolism and drug transport), care should always be taken to avoid maternal pharmacokinetic variability. The toxic effects were discrepant between the dizygotic twins, suggesting additional fetus-specific pharmacokinetic/pharmacodynamic factors in doxorubicin toxicity.

show abstract

“…[90][91][92][93] A wide range of DNA nanostructures have been used to create chemotherapeutic drugloading platforms, as well as for aptamer-based delivery for the specic uptake of drugs in vivo. 94 Doxorubicin (DOX) as a typical chemotherapeutic anticancer drug is widely used in cancer treatment, as it interacts with DNA and restrains macromolecular biosynthesis. 95 A DNA icosahedra nanostructure has been used as the nanocarrier of DOX by assembling motifs, demonstrating it as an efficient and specic strategy for epithelial cancer cells.…”

Section: Dna Biosensorsmentioning

confidence: 99%

Growing prospects of DNA nanomaterials in novel biomedical applications

et al. 2019

View full text Add to dashboard Cite

show abstract

Human placental cell and tissue uptake of doxorubicin and its liposomal formulations

Cited by 34 publications

References 40 publications

Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin

Significantly enhanced tumor cellular and lysosomal hydroxychloroquine delivery by smart liposomes for optimal autophagy inhibition and improved antitumor efficiency with liposomal doxorubicin

Maternal ABVD chemotherapy for Hodgkin lymphoma in a dichorionic diamniotic pregnancy: a case report

Growing prospects of DNA nanomaterials in novel biomedical applications

Contact Info

Product

Resources

About