The nanodrugs transdermal delivery is affected by its size and shape which further decide physical steadiness
and their cellular uptake (Escobar Chavez et al 2012). Nanoformulations can be
delivered concurrently using different means/routes owing to their particle
size and physicochemical properties (Borali 2010). Skin anatomical features
only allows free distribution of particles <5-7 nm size through transcellular route (Bouwstra and Ponec 2006, Johnson et al 1997), ?36 nm for intercellulat route  (Cevc 2004, tang et al. 2001) and > 3-10 µm for transfollicular route. Particles of smaller size
are preferred since they make available larger surface area hence can have high
drug loading capacity. Attama et al (2007) reported that low particle size solid lipid nanodispersions  (SLN) are more stable and well accepted in vivo and active
formulkation had high drug concentration (Attama AA, Schicke BC, Paepenmüller T, Müller-Goymann
CC (2007) Solid lipid nanodispersions containing mixed lipid core and a polar
heterolipid: Characterization. Eur. J. Pharm. Biopharm. 67: 48-57). Maestrelli et al (2009), who investigated ethosomes
prepared by different techniques made similar conclusions and found that small
unilamellar vesicles (SUVs) drug efficacy of benzocaine (BZC) was owing to its
small size, higher surface area which led to more intimate contact with the
epithelium for longer duration of time for therapeutic action (Maestrelli
F, Capasso G, Gonzalez-Rodriguez ML, et al., (2009) Effect of
preparation technique on the properties and in vivo efficacy of
benzocaine-loaded ethosomes. J Liposome Res 19(4): 253-60).  Desai et al.
(2010) and Baroli (2010) concluded that lipophilic nanoparticles have high
partition coefficient and drugs having molecular weight <600 Da are best suited for TDDS. Nanoparticles come in different shapes like spherical, ellipsoidal, triangular, needle shaped, cubic and prism like. They are not always rigid (e.g. lipid particles) and deformable. The shape as well as orientation of the nanoparticles greatly affects their aggregation, penetration route and diffusion coefficient (Baroli 2010). Using newer methods of nanomaterial synthesis, nanoparticles of preferred size and shape for TDDS can be engineered. ZETA POTENTIAL Zeta potential is defines as the number of charges a particle has and particle size distribution and zeta potential of nanoformulations decides the dispersion steadiness of the non-aqueous suspension Attama AA, Schicke BC, Paepenmüller T, Müller-Goymann CC (2007) Solid lipid nanodispersions containing mixed lipid core and a polar heterolipid: Characterization. Eur. J. Pharm. Biopharm. 67: 48-57. SIZE DISTRIBUTION Preparation methods and synthesis conditions (like temperature, dispersing medium, stirring rate and viscosity of the organic and aqueous phases) affect the size distribution of nanoparticles formed by different systems. Pinto Reis C, Nuefeld RJ, Ribeiro AJ, et al., (2006) Nanoencapsulation 1. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine. 2: 8-21, Maestrelli F, Capasso G, Gonzalez-Rodriguez ML, et al., (2009) Effect of preparation technique on the properties and in vivo efficacy of benzocaine-loaded ethosomes. J Liposome Res 19(4): 253-60.