Characterization and application in drug delivery of non-phospholipid vesicles and their structural changes

The basis of the success of pharmacotherapy is the design of an appropriate delivery system, that targets the drug to the site of action at an optimum concentration for a determined time interval. In the last years liposomal and niosomal vesicles have been extensively studied, in the first time as model biomembranes and actually as therapeutic drug carrier systems able to reduce toxicity of drugs by an alteration in their pharmacokinetics, to modify drug delivery and to prolong its action at the target site. In particular non ionic surfactant vesicles (niosomes) are now widely studied as alternative to liposomes; niosomes in fact show numerous advantages over the liposomal vesicles such as lower costs and higher chemical stability; furthemore vesicle aggregation and fusion usually occur at a remarkable lower rate for niosomes than for liposomes. In our studies we have used non ionic surfactant vesicles obtained by polysorbate 20 (Tween 20) and cholesterol. Tween 20 was thought not able to form vesicular structures, but in our laboratory was demonstrated that it was possible to obtain unilamellar vesicles when an equimolar amount of cholesterol was used. That is in accordance with the observation that a cone shaped amphiphile plus a wedge shapes one (cholesterol) cooperate to form bilayer membranes in vivo (1). Furthermore we have modified vesicular systems to obtain pH-sensitive vesicles (2), negative (3) and coated vesicles (4), to satisfy different therapeutic needs. Although we have prepared non ionic surfactant vesicles using other molecules characterized by different HLB values. All the vesicles studied were characterized by means of dynamic light scattering, SAXS, fluorescence and anisotropy analysis using appropriate fluorescent probes. Characterized vesicles were then studied on cells or in “in vitro” systems. In our studies we have demonstrated that our systems were useful to obtain specific delivery, due to their structural characteristics. (1) Israelachvili J. N., Marcelja S., Horn R.G. “Physical principles of membrane organization”. Q. Rev. Biophys. 13, 121-200 (1980) (2) M. Carafa, L. Di Marzio, C. Marianecci, B. Cinque, G. Lucania, K. Kajiwara, M.G. Cifone, E. Santucci. “Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell interaction”. Eur. J. Pharm. Sci. 28, 385-393 (2006). (3) M. Carafa, E. Santucci, F. Alhaique, T. Coviello, E. Murtas, F. M. Riccieri, G. Lucania, M. R. Torrisi. “Preparation and properties of new unilamellar non-ionic/ionic surfactant vesicles” Int. J. Pharm. 160, 51-59 (1998). (4) M.Carafa, C. Marianecci, V. Annibaldi, A. Di Stefano, P.Sozio, E. Santucci. “Novel O-palmitoylscleroglucan-coated liposomes as drug carriers: development, characterization and interaction with leuprolide”. Int. J. Pharm. 325, 155-162 (2006).