Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach

Silva, Juliana de Oliveira; Miranda, Sued Eustáquio Mendes; Leite, Elaine Amaral; Sabino, Adriano de Paula; Borges, Karina Braga Gomes; Cardoso, Valbert Nascimento; Cassali, Geovanni Dantas; Grabe‐Guimarães, Andrea; Oliveira, Mônica Cristina; Barros, André Luís Branco de

doi:10.1016/j.taap.2018.05.037

Cited by 31 publications

(28 citation statements)

References 47 publications

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“…Hence, the TfR-targeted liposomes coloaded with doxorubicin and verapamil were able to reverse drug resistance and selectively target cancer cells [106]. pH-sensitive liposome doxorubicin (SpHL-DOX) has been reported to reduce the serious cardiotoxic effects of DOX in preclinical trial [107].…”

Section: Nps Conjugated With Topoisomerase Inhibitor Drugsmentioning

confidence: 99%

Cancer Nanomedicine: A New Era of Successful Targeted Therapy

El-Readi

Althubiti

2019

Journal of Nanomaterials

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Cancer is considered as one of the most challenging health care problems. Though there are many approved drugs that can be used for cancer therapy, drug resistance and delivery are among of the barriers of the treatment. In addition, pathological characteristics of tumors and their abnormal blood vessel architecture and function also reduce the efficiency of the conventional cancer treatment. Therefore, looking for techniques that can increase the efficacy of the therapy such as nanoparticles (NPs) is vital. NPs have many properties such as their small size, ability to load various drugs and large surface area, and ability to increase the absorption of conjugated. Therefore, the NPs have been considered as excellent tumor-targeting vehicles. The recent nanoscale vehicles include liposomes, polymeric nanoparticles, magnetic nanoparticles, dendrimers, and nanoshells; lipid-based NPs have been used as conjugates. There are few examples of approved conjugated anticancer NPs including AmBisome® (amphotericin B liposomal) and Doxil® (liposomal doxorubicin). There are many other conjugated anticancer drugs at different stages of clinical trials for treatment of various cancers. This review will discuss the properties of different NPs in cancer treatment and their benefits of overcoming multidrug resistance. In addition, recent advances of using nanomedicine in different approaches of cancer treatment such as chemotherapy, radiotherapy, and immunotherapy will be highlighted in this review.

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Section: Nps Conjugated With Topoisomerase Inhibitor Drugsmentioning

confidence: 99%

Cancer Nanomedicine: A New Era of Successful Targeted Therapy

El-Readi

Althubiti

2019

Journal of Nanomaterials

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“…One example is the drug doxorubicin (DOX), an anthracycline antibiotic, which intercalates with DNA, interrupts topoisomerase II activity and induces free radicals. These effects induce oxidative damages and DNA double-strand breaks [1][2][3][4][5] in target cells, which in turn, inhibit cell proliferation, induce cell cycle arrest and/or lead to cellular apoptosis [6,7].…”

Section: Introductionmentioning

confidence: 99%

Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives

et al. 2020

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There is still a need for improving the treatment of breast cancer with doxorubicin (DOX). In this paper, we functionalized magnetic nanoparticles (MNPs) with DOX and studied the DOX-induced antitumor effects in breast cancer cells (BT474) in the presence of magnetic hyperthermia (43 °C, 1 h). We show that i) intratumoral application of DOX-functionalized MNPs (at least at a concentration of 9.6 nmol DOX/100 mm3 tumor volume) combined with magnetic hyperthermia favors tumor regression in vivo, and there is evidence for an increased effect compared to magnetic hyperthermia alone or to the intratumoral application of free DOX and ii) the presence of the pseudopeptide NucAnt (N6L) on the MNP surface might well be beneficial in its function as carrier for MNP internalization into breast cancer cells in vitro, which could further augment the possibility of the induction of intracellular heating spots and cell death in the future.

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“…These stabilizers are in ionized form (negatively charged) at physiological pH and thus intercalate in between the phosphatidylethanolamine (PE) molecules and favor the lamellar organization, resulting in the formation of liposomes. As these liposomes are exposed to acidic environment, the carboxyl group of the stabilizer is protonated resulting in the reversion of the PE molecules into inverted hexagonal phase, destabilization of the liposomes and thus the release of the contents of the liposomes [12,[22][23][24].…”

Section: Introductionmentioning

confidence: 99%

“…Doxorubicin has high anti-tumor activity but specificity is very low, which results in the serious side effects. Interestingly, DOX entrapped in liposomal formulation has shown reduced cardiotoxicity and improved specificity for the tumor area [24,[29][30][31][32][33]. However, being a weak base, its solubility in aqueous buffers changes with pH, which makes its encapsulation, in pH-sensitive liposomes, difficult.…”

Section: Introductionmentioning

confidence: 99%

Development of doxorubicin hydrochloride loaded pH-sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH-sensitivity

Rehman

Omran

Anton

et al. 2018

European Journal of Pharmaceutics and Biopharmaceutics

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This study investigates the impact of the chemical nature of lipids and additive on the formulation and properties of pH sensitive liposomes. The objective is to understand the respective role of the formulation parameters on the liposome properties in order to optimize the conditions for efficient encapsulation of doxorubicin (DOX). These liposomes should be stable at physiological pH, and disrupt in slightly acidic media such as the tumor microenvironment to release their DOX load. The major challenge for encapsulating DOX in pH sensitive liposomes lies in the fact that this drug is soluble at low pH (when the pH-sensitive liposomes are not stable), but the DOX aqueous solubility decreases in the pH conditions corresponding to the stability of the pH-sensitive liposomes. The study of pH-sensitivity of liposomes was conducted using carboxyfluorescein (CF) encapsulated in high concentration, i.e. quenched, and following the dye dequenching as sensor of the liposome integrity. We studied the impact of (i) the chemical nature of lipids (dioleoyl phosphatidyl ethanolamine (DOPE), palmitoyl-oleoyl phosphatidyl ethanolamine (POPE) and dimyristoyl phosphatidyl ethanolamine (DMPE)) and (ii) the lipid / stabilizing agent ratio (alpha-tocopheryl succinate), on the pH sensitivity of the liposomes. Optimized liposome formulations were then selected for the encapsulation of DOX by an active loading procedure, i.e. driven by a difference in pH inside and outside the liposomes. Numerous experimental conditions were explored, in function of the pH gradient and liposome composition, which allowed identifying critical parameters for the efficient DOX encapsulation in pH-sensitive liposomes.

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Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach

Cited by 31 publications

References 47 publications

Cancer Nanomedicine: A New Era of Successful Targeted Therapy

Cancer Nanomedicine: A New Era of Successful Targeted Therapy

Iron Oxide Nanoparticles as Carriers for DOX and Magnetic Hyperthermia after Intratumoral Application into Breast Cancer in Mice: Impact and Future Perspectives

Development of doxorubicin hydrochloride loaded pH-sensitive liposomes: Investigation on the impact of chemical nature of lipids and liposome composition on pH-sensitivity

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