Biodegradable nanoparticles as a delivery system for cyclosporine: preparation and characterization

Cyclosporine (CyA) was incorporated into polycaprolactone nanoparticles (PC L-NP) in order to increase its oral bioavailability and to control drug dis tribution, thereby potentially reducing its toxicity. Prior to in vivo stud ies, the carrier was optimized and characterized by using different techniq ues. Light scattering (LS) and transmission and scanning electron microscop y (TEM and SEM) indicated the NP were spherical in shape with a mean size o f similar to 100 nm. The influence of the solvent evaporation conditions an d the polymer and drug amounts on CyA incorporation was established in orde r to optimize drug loading. When acetone and excess water were removed at c onstant temperature, no aggregation phenomena were observed. A value of 180 mg PCL was the minimum polymer amount necessary to encapsulate 95% of the drug initially added to the preparation. Under these conditions, HPLC analy sis revealed that similar to 130 mu g CyA per mg PCL were incorporated for a total CyA concentration of 2.5 mg/ml, being part of the drug adsorbed ont o the particle surface. No structural changes or instability of the compone nts during NP preparation were detected by gel permeation chromatography (G PC) and differential scanning calorimetry (DSC). However, GPC studies showe d a competition between poloxamer and CyA for adsorption onto the carrier. In addition, DSC results suggested that at least part of the drug associate d to NP remained in its crystal form. Therefore, CyA-loaded NP were easily manufactured and characterized and allow for the administration of therapeu tic drug doses to experimental animals.