Preparation of alendronate liposomes for enhanced stability and bioactivity: in vitro and in vivo characterization.

Liposomes containing bisphosphonates have been shown to deplete circulating monocytes and reduce experimental restenosis. However, acceptable shelf life was not achieved, and the disruption extent and rate of the vesicles in the circulation has not been examined. Designing an optimal liposomal formulation in general, and for an anti-inflammatory effect in particular, requires careful consideration of the factors that contribute to their in vitro stability and integrity in the blood after injection.

A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles.

The commonly utilized techniques for encapsulating hydrophilic molecules in NP suffer from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. We hypothesized that combining the double emulsion system with a partially water-soluble organic solvent, could result in better encapsulation yield of hydrophilic molecules in nano-sized NP, and the utilization of both biocompatible surfactants and solvents. As a model drug we used alendronate, a hydrophilic low MW bisphosphonate.

Single and double emulsion manufacturing techniques of an amphiphilic drug in PLGA nanoparticles: formulations of mithramycin and bioactivity.

Formulation of hydrophilic compounds in nanoparticles is problematic due to their escape to the external aqueous phase. The certain amphiphilic nature of mithramycin, utilized clinically in cancer, makes its incorporation into nanoparticles an interesting challenge, elucidating the formulation factors of amphiphilics in nanoparticles. We hypothesized that mithramycin nanoparticles could provide more effective therapy of restenosis due to its antiproliferating and potential monocyte inhibition properties.

Nanospheres of a bisphosphonate attenuate intimal hyperplasia.

The present study explored a novel strategy for attenuation of restenosis after arterial injury by a bisphosphonate encapsulated in polymeric nanoparticles (NP) for transient selective depletion of macrophages. A bisphosphonate (BP), 2-(2-Aminopyrimidino) ethyldiene-1,1-bisphosphonic acid betaine (ISA), was successfully formulated in 400 nm sized polylactide/glycolide-based NP with high yield (69%) and entrapment efficiency (60% w/w). ISA NP, but not blank NP or free ISA, exhibited specific and significant cytotoxic effect on macrophages-like RAW 264 cells, in a dose-dependent manner, with no inhibitory effect on the growth of smooth muscle cells (SMCs).

Alendronate-loaded nanoparticles deplete monocytes and attenuate restenosis.

Systemic transient depletion of monocytes and macrophages by liposome-encapsulated bisphosphonates (BPs), reduces neointimal formation in experimental restenosis. The aim of this study was to examine the antirestenotic effect of a polymeric nanoparticulate formulation containing the BP alendronate (ALN). The BP was successfully formulated in polylactide-co-glycolide (PLGA) nanoparticles (NP).