Physical and chemical stability of drug nanoparticles

Nanoparticle manufacturing industries use well-established synthesis protocols or methodology as much as possible. The nanomaterials have unique physical and chemical properties at the atomic and molecular levels which often interfere with the standardized methods and compromise the reproducibility of the results. This chapter provides details of the challenges and associated problems which usually arise during the characterization of the nanomaterials and ways to resolve the issues with an emphasis on minimizing the associated interferences.

Methods for characterization of nanoparticles

Delivery of serotonin to the brain by monocytes following phagocytosis of liposomes.

Physicochemical parameters affecting liposomal bisphosphonates bioactivity for restenosis therapy: Internalization, cell inhibition, activation of cytokines and complement, and mechanism of cell death

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 An improved liposomal alendronate formulation was prepared by a modified thin lipid film hydration technique followed by extrusion, resulting in relatively smaller size vesicles, narrow size distribution, and low drug to lipid ratio in comparison to the reverse phase evaporation method In order to rule out premature leakage of the drug, the integrity of the vesicles was examined by means of size-exclusion chromatography in vitro and in vivo, with subsequent analysis of size, drug (fractions of encapsulated and free) and lipid concentrations Vesicles were found to be stable in serum, with 15 ± 3% leakage of the drug after 10 min in rabbit’s circulation, and intact liposomes were detected in the circulation 24 h following administration It is concluded that the new formulation results in increased stability (25 years) as determined by the insignificant changes in vesicle size, drug leakage, lipid and drug stability, in vitro bioactivity (macrophages inhibition), as well as in vivo in depleting circulating monocytes and inhibition of restenosis in rabbits Our in vitro stability results regarding dilution in serum paralleled in vivo data Thus, in vitro assessment may provide a valuable tool in assessing in vivo integrity of liposomal formulations

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Idit Levi

Papers

Nanosuspensions of alendronate with gallium or gadolinium attenuate neointimal hyperplasia in rats