Effects of Linkers on the Development of Liposomal Formulation of Cholesterol Conjugated Cobalt Bis(dicarbollides)

Boron neutron capture therapy (BNCT) remains an important treatment arm for cancer patients with locally invasive malignant tumors. This therapy needs a significant amount of boron to deposit in cancer tissues selectively, sparing other healthy organs. Most of the liposomes contain water-soluble polyhedral boron salts stay in the core of the liposomes and have low encapsulation efficiency. Thus, modifying the polyhedral boron core to make it hydrophobic and incorporating those into the lipid layer could be one of the ways to increase drug loading and encapsulation efficiency. Additionally, a systematic study about the linker-dependent effect on drug encapsulation and drug-release is lacking, particularly for the liposomal formulation of hydrophobic-drugs. To achieve these goals, liposomal formulations of a series of lipid functionalized cobalt bis(dicarbollide) compounds have been prepared, with the linkers of different hydrophobicity. Hydrophobicity of the linkers have been evaluated through logP calculation and its effect on drug encapsulation and release have been investigated. The liposomes have shown high drug loading, excellent encapsulation efficiency, stability, and non-toxic behavior. Release experiment showed minimal release of drug from liposomes in phosphate buffer, ensuring some amount of drug, associated with liposomes, can be available to tumor tissues for Boron Neutron Capture Therapy. (C) 2020 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Automated summary

Boron neutron capture therapy is an important treatment for cancer patients, requiring a significant amount of boron to be selectively deposited in cancer tissues. Modifying the polyhedral boron core to be hydrophobic and incorporating it into the lipid layer can increase drug loading and encapsulation efficiency. Additional studies on linker-dependent effects and hydrophobicity are needed for further development of liposomal formulations for hydrophobic-drugs.