FOCUS ON NANOSTRUCTURED LIPID CARRIERS AND MONOOLEIN AQUEOUS DISPERSIONS

Nowadays, everyone feels the impact of nanotechnology in his life. There is a trend that urges people to revisit many research areas with a nano-view, in order to understand how the same thing can work at nano- level. This phenomenon is revolutionizing pharmaceutical sciences and many drugs are being reformulated for possibilities of delivering as a nanosystem. In recent years, a particular attention has been focused on new generations of lipid nanoparticles such as nanostructured lipid carriers (NLC), a second generation of solid lipid nanoparticles (SLN), and monoolein aqueous dispersions (MAD), derived from the mesophases originated from the system monoolein/water/poloxamer. In this thesis different NLC, SLN or MAD formulations were developed as drug delivery systems specifically for antiparkinson or antimycotic drugs, in order to prolong their action and reduce the side effects. Bromocriptine (BC), new synthetized L-DOPA derivatives (Der-A, Der-B, Der-C and Der-D) or Clotrimazole (CLO) have been alternatively chosen as model drugs. Physical and chemical characterizations have been performed on the obtained formulations. In vitro and in vivo studies permitted to obtain release kinetics and evaluate the effectiveness of nanoparticulate systems. BC containing NLC and MAD showed high entrapment efficiency and X-ray diffraction analyses demonstrated that the presence of BC did not affect the scattering profile. In this case, different in vitro experimental approaches were evaluated, showing that the in vitro release of poorly water soluble drugs (as BC) is more affected by the composition of the receiving phase (i.e. in term of presence of water miscible polar organic solvents) rather than by the experi modality adopted for the in vitro determinations. In vivo studies demonstrated that only BC-NLC were able to markedly attenuate motor deficit in 6-OHDA hemilesioned rats, suggesting that NLC represent a more effective carrier to prolong the half-life of BC in vivo. All L-DOPA derivatives were successfully incorporated in NLC. The produced formulations resulted homogeneous in terms of size and remain stable until two months from the preparation. Morphological characterization highlighted that no substantial difference characterized empty and derivatives containing NLC. In vitro kinetics release highlighted that NLC were able to release the contained derivatives in a controlled manner and permit to select Der-A for in vivo tests. In vivo tests demonstrated that the Der-A possess antiparkinson activity. The inclusion of Der-A in SLN, performed using three different concentrations of prodrug, showed different entrapment efficiencies depending on the quantity of active employed. Calorimetric test evidenced an effective interaction between lipid phase and the prodrug. In vitro studies demonstrated a controlled release of Der-A from SLN, also thanks to the extension of the half-life of the prodrug. CLO was incorporated both in MAD and in NLC with high recovery. Shelf life stability evidenced that the solid matrix of NLC enabled to control drug degradation better than MAD. In vitro experiments on candida cells demonstrated that CLO-MAD and CLO-NLC exhibit a higher activity than the free drug. The gelification of CLO containing nanoparticles permitted to obtain formulations able to remain on the mucosa surface. Micro calorimetric assays confirmed that poloxamer formulated gels are able to change their structure, with a rapid passage from liquid to solid (crystalline) form at a temperature lower than vaginal temperature, allowing a selective action in the site of application. Finally it is noteworthy that the production of CLO-NLC poloxamer gel is simple and suitable for industry scaling up.