PHARMACEUTICAL NANOTECHNOLOGY Development, Characterization, and In Vitro and In Vivo Evaluation of Benzocaine- and Lidocaine-Loaded Nanostructrured Lipid Carriers CARMELO PUGLIA, 1 MARIA GRAZIA SARPIETRO, 2 FRANCESCO BONINA, 1 FRANCESCO CASTELLI, 2 MAGDA ZAMMATARO, 1 SANTINA CHIECHIO 1 1 Department of Pharmaceutical Sciences, University of Catania, Catania, Italy 2 Department of Chemical Sciences, University of Catania, Catania, Italy Received 8 September 2010; revised 2 November 2010; accepted 4 November 2010 Published online 10 December 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/jps.22416 ABSTRACT: The present study concerns the in vitro and in vivo evaluation of benzocaine (BENZO) and lidocaine (LIDO) topical delivery from nanostructured lipid carriers (NLCs). Morphology and dimensional distribution of NLCs have been, respectively, characterized by differential scanning calorimetry (DSC) and photon correlation spectroscopy. The release pat- tern of BENZO and LIDO from NLCs was evaluated in vitro determining drug percutaneous absorption through excised human skin. Radiant heat tail-flick test was carried out in mice to determine the antinociceptive effect of BENZO and LIDO from NLC. DSC studies revealed that the inner oil phase of NLC plays a significant role in stabilizing the particle architecture and in- creasing the drug solubility. In vitro evidences show that BENZO and LIDO, when incorporated in viscosized NLC dispersions, exhibited a lower flux with respect to formulations containing the free drugs in the aqueous phase. In vivo study enabled to demonstrate that BENZO and LIDO can be released in a prolonged fashion when incorporated into lipid carriers. The results obtained pointed out NLC capability to act as an effective drug reservoir, thus prolonging the anesthetic effect of BENZO and LIDO. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1892–1899, 2011 Keywords: Calorimetry (DSC); Particle sizing; Percutaneous; Ultrasound; Lipids; Nanos- tructured lipid carriers; Radiant heat tail-flick test; Dermal targeting. INTRODUCTION Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are interesting colloidal carriers presenting several attractive features for topical drug delivery. 1–3 First, these carriers are composed of no toxic biodegradable lipids, which are excipients gen- erally used in commercially available topical prepa- rations. Furthermore, because of their solid lipid matrix, a controlled release from these carriers is possible. This becomes an important tool when it is necessary to supply the drug over prolonged period of time, to reduce systemic absorption, and when drug produces irritation in high concentration. 4–6 Although both SLNs and NLCs are submicron size particles (40–1000 nm) and are based on solid lipids, Correspondence to: Carmelo Puglia (Telephone: 399-573-84273; Fax: 399-522-2239; E-mail: capuglia@unict.it) Journal of Pharmaceutical Sciences, Vol. 100, 1892–1899 (2011) © 2010 Wiley-Liss, Inc. and the American Pharmacists Association they can be distinguished by their inner structure. NLCs show a more complex architecture that guar- antees higher stability and drug loading compared with “old” SLNs. 7 This “second generation” of lipid particles is composed of a solid lipid and an oil phase that seems to be organized in nanocompartments in- side solid lipid matrix. Some evidences suggest that, after the formulation, the drug remains in the liq- uid lipid surrounded by the solid lipid. 8 This provides some degree of mobility to the drug that contributes to stability even when the solid lipid undergoes poly- morphic changes. Another important feature of NLCs is their abil- ity to control the release of active compounds from the matrix. 7 Similar evidences were demonstrated in previous works of our research group regarding the evaluation of the percutaneous absorption of differ- ent nonsteroidal anti-inflammatory drugs from NLCs. The results showed a decreased permeation of the ac- tive compounds and the formation of a drug reservoir 1892 JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 100, NO. 5, MAY 2011