Liposomes as drug delivery vehicles for boron agents

The successful treatment of cancer by boron neutroncapture therapy (BNCT) requires the selective concentration ofboron-10 within malignant tumors. The potential of liposomesto deliver boron-rich compounds to tumors has beenassessed by examination of the biodistribution of borondelivered by liposomes in tumor-bearing mice. Small unilamellarvesicles have been found to stably encapsulate highconcentrations of water-soluble ionic boron compounds. Alternatively, lipophilicboron-containing species have been embedded within the phospholipidbilayer of liposomes, and both hydrophilic and lipophilicboron compounds have been incorporated within the sameliposome formulation.The biodistribution of boron was determined at severaltime points over 48 hr after i.v. injection ofliposomal suspensions in BALB/c mice bearing EMT6 tumors.The tumor-selective delivery of boron by the liposomeswas demonstrated as tumor-boron concentrations increased for severalhours post-injection. Even at the low injected dosesemployed (6–18 mg boron/kg body weight) therapeutic tumor boronconcentrations were observed (>30 μg boron/g tissue) andhigh tumor/blood ratios were achieved (>5). The mostfavorable results were obtained with the polyhedral boraneNa3[a2-B20H17NH2CH2CH2NH2]. Liposomes encapsulating this species produced a tumorboron concentration of 45 μg/g tissue at 30hr post-injection,at which time the tumor/blood boron ratio was9.3.