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Dual functionalized liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment of glioblastoma. | LitMetric

Dual functionalized liposomes for efficient co-delivery of anti-cancer chemotherapeutics for the treatment of glioblastoma.

J Control Release

Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo 58105, ND, USA. Electronic address:

Published: August 2019

AI Article Synopsis

  • Glioblastoma is a highly aggressive brain tumor with a poor prognosis, partly due to the challenges posed by the blood-brain barrier (BBB) limiting drug delivery.
  • The study developed a dual functionalized liposomal delivery system designed with transferrin and a cell-penetrating peptide to improve drug translocation across the BBB, specifically loading it with doxorubicin and erlotinib.
  • Results showed that this system significantly increased drug accumulation in the brain and reduced tumor size by about 90% in mice, leading to longer survival times without noticeable toxicity, suggesting it could greatly improve glioblastoma treatment outcomes.

Article Abstract

Glioblastoma is a hostile brain tumor associated with high infiltration leading to poor prognosis. Anti-cancer chemotherapeutic agents have limited access into the brain due to the presence of the blood brain barrier (BBB). In this study, we designed a dual functionalized liposomal delivery system, surface modified with transferrin (Tf) for receptor mediated transcytosis and a cell penetrating peptide-penetratin (Pen) for enhanced cell penetration. We loaded doxorubicin and erlotinib into liposomes to enhance their translocation across the BBB to glioblastoma tumor. In vitro cytotoxicity and hemocompatibility studies demonstrated excellent biocompatibility for in vivo administration. Co-delivery of doxorubicin and erlotinib loaded Tf-Pen liposomes revealed significantly (p < 0.05) higher translocation (~15%) across the co-culture endothelial barrier resulting in regression of tumor in the in vitro brain tumor model. The biodistribution of Tf-Pen liposomes demonstrated ~12 and 3.3 fold increase in doxorubicin and erlotinib accumulation in mice brain, respectively compared to free drugs. In addition, Tf-Pen liposomes showed excellent antitumor efficacy by regressing ~90% of tumor in mice brain with significant increase in the median survival time (36 days) along with no toxicity. Thus, we believe that this study would have high impact for treating patients with glioblastoma.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732022PMC
http://dx.doi.org/10.1016/j.jconrel.2019.06.033DOI Listing

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