Production of lipospheres for bioactive compounds delivery

Lipospheres (LS), have been proposed as new type of fat-based matrix developed for drug delivery of bioactive compounds. LS combine the advantages of polymeric nanoparticles, fat emulsions and liposomes avoiding some of their disadvantages, such as cytotoxic effects after phagocytosis, toxic effects of organic residues after the production of polymers, lack of large industrial scale production. Due to their large particle size range (comprised between 0.2-500 µm), LS can be administered by different routes, such as oral, subcutaneous, intramuscular, topic or used for cells encapsulation. The targeting to phagocytic cells could be approached by LS for the treatment of many infectious deseases (i.e. AIDS) and for the administration of hormones, such as growth factors. In addition, the encapsulation of some antibiotics, such as tetracycline, for the treatment of periodontal diseases and enteric infections could be facilitated. The in vivo distribution of LS demonstrated an high affinity to vascular wells (including capillaries), to inflamed tissues and to granulocytes. This study evaluate (a) the production of LS obtained by emulsion-melt dispersion and by solvent evaporation, (b) the influence of preparation parameters on liposphere morphology and (c) the microparticles' release of model drugs (retinyl acetate, progesteron and sodium cromoglycate). To obtain a biocompatible formulation for humans, triglycerides and monoglycerides were chosen as biomaterials, due to their high biocompatibility and high physicochemical stability. Our results demonstrated that the morphological characteristics of the produced LS are influenced by (a) the type of lipid matrix used, (b) stabilizer, (c) the stirring speed and (d) type of paddle strirrer. Nevertheless, LS can entrap efficiently both hydrophobic and hydrophilic drugs and control the release of the encapsulated drug. In addition, the activity of the drug towards the target is increased and the cytotoxic systemic effects minimalized. The encouraging results obtained in this study could propose LS for future clinical trials, especially in the vehiculation of anti-infectives and hormones.