Liposomal formulations containing sodium mercaptoundecahydrododecaborate (BSH) for boron neutron capture therapy

Abstract

Sodium mercaptoundecahydrododecaborate or BSH is a compound most widely used for boron neutron capture therapy (BNCT). Liposome formulations containing BSH, with or without steric stabilization, were prepared as potential agents for delivery of boron compounds for BNCT. Liposomes composed of DPPC/CHOL in a molar ratio 1:1 (PEG concentration: 5 mol%) were prepared having an average diameter in the range of 100-110 nm 200 mu L of liposomes (l.88 mg phospholipid/mouse and 3.5-5.8 mg BSH/kg body weight) were injected in mice via the tail vein. Both types of liposomes resulted in a significant improvement in the circulation time of BSH compared to that obtained previously after injecting free BSH. The mean percent injected BSH remaining in circulation at the end of 24 h was 19% for the PEG-liposomes compared to the corresponding value of 7% for the conventional liposomes. The mean percent uptake by the liver and spleen was not significantly different for the two types of liposomes; the blood/RES ratios were higher for the PEG-liposomes at all time points indicating that a higher fraction of injected BSH was available in circulation. The PEG-liposomes could be further explored as a means of enhance boron drug delivery to tumor cells for BNCT.

Receptor-Targeted Liposomal Delivery of Boron-Containing Cholesterol Mimics for Boron Neutron Capture Therapy (BNCT)

“…Target compounds II and III were obtained in a similar fashion, and yields for all three target compounds ranged from 46% to 56%. All intermediates and target compounds were purified effectively by silica gel column chromatography and characterized by 1 H NMR, 13 C NMR, and HR-EIMS. An important criterion for the synthesis of compounds I-III was practicability.…”

“…Purification by silica gel flash chromatography (hexanes/ethylacetate 8:2; R f : 0.4) gave II in 50% yield. 1 13 RMS Fit of Cholesterol with Compounds I-III ( Figure 2). Hyperchem 7.51 (Hypercube, Inc., Gainsville, FL) was used on a Dell Inspiron 4100 to produce the rms fit of cholesterol with the carboranyl cholesterol mimics I-III.…”

Boron neutron capture therapy assisted by boron-conjugated nanoparticles

“…23 In particular, poly(ethylene glycol) (PEG)-modified liposomes encapsulating BSH in their interior have attracted attention as effective nano-sized carriers of 10 B atoms because of their biocompatibility, long blood-circulation time and effective accumulation in tumors through EPR effects. 24 Maruyama et al prepared a transferrin-conjugated PEG-modified liposome encapsulating BSH to enhance the specificity of the liposome against tumors [25][26][27] because it is well-known that the transferrin receptor concentration on tumor cells is much higher than that on normal cells. 28 Although the PEGmodified liposomes encapsulating BSH showed higher accumulation in the tumor region than free BSH through the EPR effect, the therapeutic efficacy of the BSH-encapsulated liposomes remains controversial because of the leakage of the encapsulated BSH from the liposome into the blood stream caused by the high ion osmotic pressure of the BSH-loaded interior of the liposome.…”

Cell Culture and Animal Studies for Intracerebral Delivery of Borocaptate in Liposomal Formulation

“…An advanced pharmaceutical formulation of a boron compound administered directly to the tumor site within the brain parenchyma bypasses the BBB, elevates local B 10 concentration, and assures that normal tissues in the rest of the body will not be exposed to the cytotoxic products of radiation. Liposomes offer an advantage over other formulations because they can carry relatively large quantities of therapeutic agents and facilitate their delivery to cells (Mehta, Lai, and Lu 1996). Our early study showed that intracerebral injection of liposomes containing borocaptate (BSH), a boron cage compound (Figure 1), was safe (Mehta, Olson, and Lu 1995).…”