Luc Grislain

Pharmacokinetics and Distribution of a Biodegradable Drug-carrier

Abstract This paper describes tissue distribution, blood clearance and excretion of biodegradable cyanoacrylic nanoparticles. After intravenous administration, nanoparticles were rapidly cleared from the blood stream and concentrated mainly in the reticuloendothelial system. When administrated subcutaneously, nanoparticles seemed to avoid the liver and the spleen whereas they concentrated in the gut wall. Whole body autoradiography performed on Lewis Lung carcinoma-bearing mice showed progressive accumulation of the carrier in tumoral tissue. Furthermore a high level of radioactivity was found in the metastatic lungs of cancerous animals, whereas no lung accumulation was observed in healthy mice. Data are given concerning the enzymatic contribution to the degradation of the nanoparticles in vivo.

The stenlying effect of high hydrostatic pressure on thermally and hydrolytically labile nanosized carriers.

AbstractPurpose. To investigate whether high hydrostatic pressure (HHP) treatment allows the sterilization of thermosensitive polymer nanoparticle suspensions without jeopardizing their physicochemical integrity. Methods. Application of HHP was explored on a wide variety of thermosensitive poly(cyanoacrylate) nanoparticles, varying by their type (nanospheres or nanocapsules), by their preparation method (nanoprecipitation or emulsion/solvent evaporation), as well as by their surface characteristics. Physicochemical characterization before and after pressurization included turbidimetry, size measurement, zeta potential, scanning electron microscopy and infrared analysis. A sterility test also conducted according to pharmacopoeial requirements on an importantly contaminated nanoparticle suspension. Results. Poly(cyanoacrylate) nanoparticles appeared to be extremely baroresistant. Continuous or oscillatory HHP treatment up to 500 MPa during 30 min induced generally neither physical, nor chemical damage. However, precautions should be taken when surface modifiers are adsorbed onto nanoparticles, as a layer destabilization may occur. Finally, this process allowed the successful inactivation of vegetative bacteria, yeast, and fungi. Conclusions. This work proposes HHP as a new method for polymer drug carriers sterilization, taking into account that further exploration in this area is needed to propose novel protocols for spores inactivation.

Effects of High Hydrostatic Pressure on Several Sensitive Therapeutic Molecules and a Soft Nanodispersed Drug Delivery System

AbstractPurpose. According to the development in the last decade of industrial processes using high hydrostatic pressure (HHP) for preservation of several commercial food products, novel sterilization or decontamination processes for pharmaceutical products could be conceivable. The aim of this work is to evaluate the effects of HHP on the integrity of insulin and heparin solutions, suspension of monoclonal antibodies and Spherulites®. Methods. High performance liquid chromatography, thin layer chromatography, capillary electrophoresis assays, ELISA tests, laser granulometry and spectrophotometry analyses have been performed to compare HHP treated drugs (in a domain of pressure and temperature ranging respectively from 20 up to 500 MPa and from 20°C up to 37°C) vs. untreated ones. Results. No difference has been detected except for monoclonal antibodies that are altered above 500 MPa. Conclusions. The structure integrity of sensitive molecule due to the small energy involved by HHP and the development of industrial plants (intended for the decontamination of food products) confer to this technology the potential of a new method for sterilization of fragile drugs and an original alternative to aseptic processes and sterilizing filtration.