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Theranostics
2020;10 (10): 4308-4322.

Muscone/RI7217 co-modified upward messenger DTX liposomes enhanced permeability of blood-brain barrier and targeting glioma.

Shuangming Kang, Wenjuan Duan, Shangqian Zhang, Dawei Chen, Jianfang Feng, Na Qi
Author Information
  1. Shuangming Kang: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  2. Wenjuan Duan: Department of Pharmacy, Guilin Medical University, Guilin, 541004, China.
  3. Shangqian Zhang: Department of Pharmacy, Guilin Medical University, Guilin, 541004, China.
  4. Dawei Chen: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China.
  5. Jianfang Feng: Department of Pharmacy ,Guangxi University of Chinese Medicine, Nanning, 530299, China.
  6. Na Qi: Department of Pharmacy, Guilin Medical University, Guilin, 541004, China.
PMID: 32292496 DOI: 10.7150/thno.41322

Abstract

: The dual-targeted drug delivery system was designed for enhancing permeation of the blood-brain barrier (BBB) and providing an anti-glioma effect. As transferrin receptor (TfR) is over-expressed by the brain capillary endothelial (hCMEC/D3) and glioma cells, a mouse monoclonal antibody, RI7217, with high affinity and selectivity for TfR, was used to study the brain targeted drug delivery system. Muscone, an ingredient of traditional Chinese medicine (TCM) musk, was used as the "guide" drug to probe the permeability of the BBB for drug delivery into the cerebrospinal fluid. This study investigated the combined effects of TCM aromatic resuscitation and modern receptor-targeted technology by the use of muscone/RI7217 co-modified docetaxel (DTX) liposomes for enhanced drug delivery to the brain for anti-glioma effect. : Cellular drug uptake from the formulations was determined using fluorescence microscopy and flow cytometry. The drug penetrating ability into tumor spheroids were visualized using confocal laser scanning microscopy (CLSM). glioma-targeting ability of formulations was evaluated using whole-body fluorescent imaging system. The survival curve study was performed to evaluate the anti-glioma effect of the formulations. : The results showed that muscone and RI7217 co-modified DTX liposomes enhanced uptake into both hCMEC/D3 and U87-MG cells, increased penetration to the deep region of U87-MG tumor spheroids, improved brain targeting and prolonged survival time of nude mice bearing tumor. : Muscone and RI7217 co-modified DTX liposomes were found to show improved brain targeting and enhanced the efficacy of anti-glioma drug treatment

Keywords

RI7217 blood-brain barrier glioma liposome muscone

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MeSH Term

Animals
Antigens, CD
Blood-Brain Barrier
Brain Neoplasms
Case-Control Studies
Cell Line, Tumor
Cell Survival
Cycloparaffins
Docetaxel
Drug Delivery Systems
Drug Therapy, Combination
Glioma
Liposomes
Medicine, Chinese Traditional
Mice
Mice, Nude
Permeability
Receptors, Transferrin
Tubulin Modulators

Chemicals

Antigens, CD
CD71 antigen
Cycloparaffins
Liposomes
Receptors, Transferrin
Tubulin Modulators
Docetaxel
muscone
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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