1. Nanoemulsions as Versatile Formulations for Paclitaxel Delivery: Peroral and Dermal Delivery Studies in Rats 
Sateesh Khandavilli, Ramesh Panchagnula 
Journal of Investigative Dermatology 
Volume 127, Issue 1, Pages (January 2007)
DOI: /sj.jid
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

2. Figure 1
i.v. plasma concentration profile** of PCL administered via femoral vein (10mg/kg). Taxol formulation was injected through femoral vein over a period of 3minutes. The drug showed two-compartment disposition characterized by rapid distribution followed by slow elimination. The dose-independent parameters correlated well with literature reports (Gao et al., 2003; He et al., 2003). The AUC24-∞ was calculated from formula C24/β, and AUC0-∞=AUC0–24+AUC24-∞. **This profile is the mean±SEM of 4–5 Sprague–Dawley rats.
Journal of Investigative Dermatology  , DOI: ( /sj.jid )
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

3. Figure 2
Plasma concentration profile of PCL when administered orally as NE and its comparison with i.v. and oral Taxol. The inset graph is the magnified bottom portion in order to show clearly the plasma drug concentrations obtained by non-i.v. routes. Oral NE and Taxol plasma concentrations are mean±SEM of six rats, i.v. profile is the mean±SEM of 4–5 rats, whereas the dermal application profile is expressed as mean±SEM of four rats. NE formulation (coded as LMEV_24 in text) containing TPGS as co-surfactant was administered by various routes to calculate relative and absolute bioavailability. PCL formulation commercially available as Taxol, containing Cremophor EL and dehydrated ethanol was used as reference formulation. Oral absolute bioavailability of PCL was very low (10.62%) and improved seven times (70.25%), when administered as NE. PCL was administered at 10mg/kg dose orally and intravenously. Dermally it was administered at 8mg/kg dose. As it is a case of infinite dosing, and rate control is with skin, the amount of applied dose is not significant.
Journal of Investigative Dermatology  , DOI: ( /sj.jid )
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

4. Figure 3
The absolute bioavailability of PCL administered from various formulation via different routes of administration. The numbers indicate the absolute bioavailability of formulations. The absolute bioavailability was calculated from the ratio of AUC0-∞ of each formulation with that obtained upon i.v. administration of same dose of PCL.
Journal of Investigative Dermatology  , DOI: ( /sj.jid )
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

5. Figure 4
Distribution of PCL. Distribution of PCL into different layers of skin upon dermal administration as patch against systemic administration by i.v. route, showing regional pharmacokinetic advantage of localized delivery when compared to systemic delivery. Forty-eight hours data represent the mean±SEM of four replicates, whereas at 1hour and 4hours, one animal each was killed to obtain tissue distribution of drug. In case of i.v. dosing, each bar is the mean±SEM of four replicates. Upon i.v. administration, drug distribution is uniform in all skin layers at 1μg/4cm2, whereas peak systemic concentration is 35μg/ml. On the contrary, upon dermal application, maximum local concentration in live dermis layer reached to 10μg, whereas systemic concentrations were below 100ng/ml. This proves the regional pharmacokinetic advantage of these NEs when compared to systemic administration for the therapy of diseases involving the skin.
Journal of Investigative Dermatology  , DOI: ( /sj.jid )
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions

6. Figure 5
The irritancy evaluation of NE formulation using biophysical tools. (a) Skin local blood flow evaluation using LDV. (b) Skin barrier evaluation using TEWL. Using both tools, no significant difference was observed between naïve rats and NE-treated rats (P>0.05), indicating that formulation is non-irritant and not altering barrier irreversibly in vivo.
Journal of Investigative Dermatology  , DOI: ( /sj.jid )
Copyright © 2007 The Society for Investigative Dermatology, Inc Terms and Conditions