Publications by authors named "Lilia R C Pedrosa"

Despite the advantages of liposomal drug delivery, the bioavailability of the chemotherapeutic drugs to tumor cells is limited by their slow release from nanocarriers and low drug permeability across cell membranes. Drug encapsulation into stealth thermosensitive liposomes can improve drug delivery to tumors by combining efficient accumulation at tumors and the active release of the payload following remote heat triggering. Short-chain sphingolipids are known to enhance cellular uptake of amphiphilic drugs.

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Purpose: To improve therapeutic activity of mitoxantrone (MTO)-based chemotherapy by reducing toxicity through encapsulation in nanoliposomes and enhancing intracellular drug delivery using short-chain sphingolipid (SCS) mediated tumor cell membrane permeabilization.

Methods: Standard (MTOL) and nanoliposomes enriched with the SCS, C8-Glucosylceramide or C8-Galactosylceramide (SCS-MTOL) were loaded by a transmembrane ammonium sulphate gradient and characterized by DLS and cryo-TEM. Intracellular MTO delivery was measured by flow cytometry and imaged by fluorescence microscopy.

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Article Synopsis
  • The effectiveness of bioactive drugs in cancer treatment is limited by their ability to cross cell membranes, which often leads to therapy resistance due to insufficient drug accumulation inside cells.
  • Researchers discovered a mechanism that enhances the movement of the well-known anti-cancer drug doxorubicin across cell membranes, using lipid analogues to create a temporary channel that aids drug translocation.
  • Their findings, supported by molecular simulations and tests on genetically modified mice with breast cancer, highlight how membrane structure restricts drug efficacy and offer a potential solution for improving the effectiveness of existing cancer treatments.
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Purpose: To improve nanoliposomal-doxorubicin (DoxNL) delivery in tumor cells using liposome membrane-incorporated short-chain sphingolipids (SCS) with selective membrane-permeabilizing properties. DoxNL bilayers contained synthetic short-chain derivatives of known membrane microdomain-forming sphingolipids; C₈-glucosylceramide (C₈-GluCer), C₈-galactosylceramide (C₈-GalCer) or C₈-lactosylceramide (C₈-LacCer).

Methods: DoxNL enriched with C₈-GluCer or C₈-GalCer were developed, optimized and characterized with regard to size, stability and drug retention.

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