Liposomal alendronate

Figure 4 Hypercholesterolemic rabbit carotid artery 30 days after balloon injury. Photomicrographs of Verhoff s tissue elastin staining of (A,C) full-size and (B,D) higher magnification sections from (A,B) control, (C,D) liposomal alendronate treated (3mg/kg intravenous, at the time of injury). Control animals were treated with buffer, free BP (alendronate), or empty liposomes and grouped as control (n — 20 arteries/group, P<0.05). Abbreviation BP, bisphosphonate.

Danenberg HD, Golomb G, Groothuis A, et al. Liposomal alendronate inhibits systemic innate immunity and reduces instent neointimal hyperplasia in rabbits. Circulation 2003 108 2798-2804. 

Figure 2 Effect of liposomal formulations BPs (alendronate and clodronate), empty and free drugs on RAW 264 cell survival. Curves represent percentage of cell inhibition with different BP concentrations. Cell count in buffer only was determined to be 100% (n = 3). Abbreviation BPs, bisphosphonates. Source From Ref 69.

The rat carotid artery injured by a balloon catheter has been widely used as a model of angioplasty. The rat model is a proliferation model without foam cells (93). This form of injury causes immediate coagulation and thrombosis cascade in which platelets adhere, spread, and degranulate on the denuded surface of the artery, and approximately 24 hours later SMC begin to proliferate. Liposomal BPs, clodronate, and alendronate were injected to male sabra rats, 15 and 3mg/kg, respectively (52,69,76). Marked neointimal formation and decreased luminal area were observed in control animals. Neointima/media (N/M) ratio was 1.3 0.2, and luminal stenosis was 44 3%. LC and LA suppressed intimal growth when administered intravenously on day -1 and day 6. N/M ratios were reduced by 60% and 69% for LC and LA, respectively. 

Systemically administered liposome-encapsulated bisphosphonates (e.g., clodronate or alendronate) have been shown to be effective, in rat and rabbit models, in the prevention of restenosis. This complication frequently occurs following percutaneous coronary interventions. Thus, these compounds show considerable promise for clinical application in this area [31]. 

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