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

Rationale: 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. Methods: 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). In vivo 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. Results: 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 in vivo and prolonged survival time of nude mice bearing tumor. Conclusion: Muscone and RI7217 co-modified DTX liposomes were found to show improved brain targeting and enhanced the efficacy of anti-glioma drug treatment in vivo.

[Analysis of muscone from serum and cerebrospinal fluid of rabbits after intragastric administration of tongqiao huoxue granules].

OBJECTIVE: To analyse the muscone from serum and cerebrospinal fluid (CSF) of rabbits after intragastric administration of Tongqiao Huoxue granules (TQHXG) and provide the partial experimental reference on laying down quality standard of preparation of formula and offer new ideas on studying the relation between pharmacodynamics and its effective component of formula. METHODS: Muscone from TQHXG was qualitative identified by the methods of thin-layer chromatography (TLC) and gas chromatography (GC). Muscone from blood and CSF of rabbits was examined by GC after intragastric administration of TQHXG. Compared with standard reference material of muscone, blank serum and blank CSF, the segmental component absorbed into CSF of rabbits was confirmed. RESULTS: Spots of TQHXG on the chromatomap showed the same colour at the corresponding locality of the standard reference material. Detected by GC, chromatographic peaks appeared at the retention time of 4.8 minute in the chromatomaps of the serum with TQHXG, the CSF with TQHXG and standard reference material of muscone, while there were no chromatographic peaks in the chromatomaps of the blank serum, the blank CSF and methanol at the same time. The ingredient corresponding the chromatographic peaks at the retention time of 4.8 minute in the chromatomaps of the serum, CSF with TQHXG should be muscone. CONCLUSION: Muscone from TQHXG could penetrate blood brain barrier and could be one index of quality standard of preparation of TQHXG.