Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy

• Published in: Pharmaceutical research Vol. 36; no. 10; pp. 144 - 8
• Main Authors: Luderer, Micah John, Muz, Barbara, Alhallak, Kinan, Sun, Jennifer, Wasden, Katherine, Guenthner, Nicole, de la Puente, Pilar, Federico, Cinzia, Azab, Abdel Kareem
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2019; Springer; Springer Nature B.V
• Subjects: Animals; Antineoplastic Agents - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Boron; Boron Compounds - administration & dosage; Boron Compounds - chemistry; Boron Compounds - pharmacokinetics; Boron Neutron Capture Therapy; Cancer; Care and treatment; Cell Line, Tumor; Central Nervous System Neoplasms - metabolism; Clinical trials; Doxorubicin - chemistry; Drug Liberation; Female; Fever; Glioma; Glioma - metabolism; Glioma cells; Gliomas; Humans; Hyperthermia; Hyperthermia, Induced; Liposomes; Liposomes - chemistry; Medical colleges; Medical Law; Mice, Nude; Neutrons; Nitroimidazole; Nitroimidazoles - administration & dosage; Nitroimidazoles - chemistry; Nuclear capture; Particle Size; Permeability; Pharmacology/Toxicology; Pharmacy; Phenylalanine - administration & dosage; Phenylalanine - analogs & derivatives; Phenylalanine - chemistry; Phospholipids - chemistry; Physiological aspects; Research Paper; Temperature; Tissue Distribution; boron neutron capture therapy; thermal sensitive liposomes; boronated compound; glioma; drug delivery
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-019-2670-z

Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation. Methods Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. Results We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells. Uniquely, the 2-nitroimidazole moiety extended the tumor retention of boron content compared to BPA. Conclusion This is the first study to show the delivery of boronated compounds using TSLs for BNCT, and these results will provide the basis of future clinical trials using TSLs for BNCT.