Please cite this article in press as: Khurana, S., et al., Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam. Chem. Phys. Lipids (2013), http://dx.doi.org/10.1016/j.chemphyslip.2013.07.010 ARTICLE IN PRESS G Model CPL 4218 1–8 Chemistry and Physics of Lipids xxx (2013) xxx–xxx Contents lists available at ScienceDirect Chemistry and Physics of Lipids j ourna l h o mepa ge: www.elsevier.com/locate/chemphyslip Preparation and evaluation of solid lipid nanoparticles based nanogel for dermal delivery of meloxicam S. Khurana a , P.M.S. Bedi a , N.K. Jain b,∗ Q1 a Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar 143104, India b Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar 470003, India a r t i c l e i n f o Article history: Received 17 May 2013 Received in revised form 27 July 2013 Accepted 29 July 2013 Available online xxx Keywords: Solid lipid nanoparticles Meloxicam Skin penetration Controlled release Sustained release Carrageenan induced paw edema model a b s t r a c t The aim of the current investigation was to prepare and investigate the potential of solid lipid nanopar- ticles based gel (SLN-gel) for the dermal delivery of meloxicam (MLX). The meloxicam loaded SLN (MLX-SLN) gel was developed and characterized by means of photon correlation spectroscopy, rheome- try, and differential scanning calorimetry to determine the physicochemical properties. The behavior of SLN gel on rat skin was evaluated in vitro using Franz diffusion cells to determine the skin permeation and penetration characteristics, in vivo on mice to determine the skin tolerance by histopathological examinations. The anti-inflammatory potential of SLN gel was assessed by carrageenan induced rat paw edema test. Biophysical studies including differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were undertaken to study the interaction between the SLN gel and skin. MLX-SLN gel with nanometric particle size exhibited the controlled release abilities and simultaneously the potential to transport the drug to various skin layers. SLN gel displayed viscoelastic properties with predominantly elastic behavior and exhibited plastic flow. Biophysical studies elucidated the interaction between the SLN gel and stratum corneum (SC) lipids, and proposed the lipid bilayer fluidization as the possible mechanism for the increased penetration of meloxicam into skin. The nano-gel system showed marked anti-inflammatory activity and excellent skin tolerability. It can be concluded that SLN gel may be a promising delivery system for MLX in the treatment of inflammatory disorders. © 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Meloxicam (MLX) classified as a BCS class II drug (high permeability and poor solubility) is a potent non-steroidal anti- inflammatory (NSAID) drug used orally to alleviate the symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Arthritis, an inflammatory disorder is the most common cause of functional disability. Currently, no curative treatments of arthri- tis exist and the therapeutic objectives are mainly focused on the symptomatic treatment to relieve pain, inflammation and stiffness of joints (Quan et al., 2008; Abramson and Yazici, 2006). Following Q2 oral administration, MLX is well absorbed from the gastrointesti- nal tract with a high absolute bioavailability of 89%. In clinical trials, MLX has shown a better gastrointestinal safety profile at therapeu- tic oral doses of 7.5 and 15 mg once daily in comparison to other NSAID (Furst, 1997; Martin et al., 2000). Nonetheless, recent stud- ies pointed out that the toxicological profile of MLX is associated with gastrointestinal side effects, risk of arterial thrombotic events, ∗ Corresponding author. Tel.: +91 7582 264712; fax: +91 7582 264712. E-mail addresses: shelly pharmacy@yahoo.com (S. Khurana), jnarendr@yahoo.co.in (N.K. Jain). a functional renal failure, liver dysfunction, and skin reactions particularly at high doses and on long term treatment (Distel et al., 1996; Lanes et al., 2000). So, there is no clear comprehensive agree- ment to support their long term use in clinical practice. Since arthri- tis is a chronic disease and usually requires the administration of drug over an extended period of time so this originated the require- ment for an alternative mode of drug delivery which could over- come all the drawbacks associated with the existing oral dosage forms. Intra-articular (IA) administration of the drug (Gerwin et al., 2006) has therefore been used as an alternative. However, the need for repeated joint needling and the size and accessibility of involved joints have constrained the application of this route. Dermal admin- istration of the drug is apparently an attractive choice since it would reduce the chances of drug associated gastrointestinal and systemic side effects. Regrettably, the dermal administration of MLX is ham- pered by the barrier properties of the stratum corneum (SC). Solid lipid nanoparticles (SLNs) have gained an increasing interest as der- matological formulation for the delivery of drug molecules because of small size, biocompatibility, ability to incorporate lipophilic as well as hydrophilic drugs and controlled release properties (Utreja and Jain, 2001). They are colloidal carrier systems composed of a high melting point solid lipid/lipids as a core coated by surfactants. However, the low viscosity of SLN dispersion is disadvantageous for 0009-3084/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.chemphyslip.2013.07.010 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60