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Cited by 160Nanoparticle-Based Drug DeliveryBarrier Structure and Function StudiesRNA Interference and Gene Delivery

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

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Lakkadwala, Sushant, dos Santos Rodrigues, Bruna, Sun, Chengwen, Singh, Jagdish·2019·Journal of Controlled Release
DOI 10.1016/j.jconrel.2019.06.033PMC PMC6732022
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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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  • Liposome system with transferrin and cell-penetrating peptide modification shows around 12 and 3.3-fold increases of DOX and erlotinib delivery compared to free drugs.

    “Their liposome system thus showed around 12 and 3.3-fold increases of two chemotherapeutics (DOX and erlotinib) delivery, respectively compared to the free drugs.”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [258]

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Cited by

Sorted by citations

Authors
Lakkadwala, S., dos Santos Rodrigues, B., Sun, C., & Singh, J.
Affiliations
North Dakota State University (US)
Corresponding author
Singh, Jagdish
ORCID
Venue
Journal of Controlled Release
Publisher
Elsevier BV
Published
2019-08
Volume
307
Pages
247-260
ISSN
0168-3659 (ISSN-L)
DOI
10.1016/j.jconrel.2019.06.033
PMC
PMC6732022
OpenAlex
W2954338576
Cited by
160
References
1
Citations by year
2026: 11 · 2025: 26 · 2024: 25 · 2023: 24 · 2022: 23 · 2021: 26 · 2020: 21 · 2019: 4
FWCI
5.24
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Controlled Release (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
Keywords
glioblastoma, liposomes, dual drug delivery, doxorubicin, erlotinib, transferrin receptor, cell-penetrating peptides, penetratin, blood-brain barrier, receptor-mediated transcytosis, brain tumors, tissue distribution, hemocompatibility, antitumor efficacy
MeSH terms
Erlotinib Hydrochloride, Animals, Antineoplastic Agents, Brain, Brain Neoplasms, Cell Survival, Doxorubicin, Female, Glioblastoma, Humans, Liposomes, Male, Mice, Nude, Phosphatidylethanolamines, Polyethylene Glycols, Tissue Distribution, Transferrin, Cell Line, Tumor, Nanoparticles, Cell-Penetrating Peptides

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