Research Article Biodegradable Ingredient-Based Emulgel Loaded with Ketoprofen Nanoparticles Rabia Gul, 1 Naveed Ahmed, 1 Naseem Ullah, 1 Muhammad Ijaz Khan, 1,2 Abdelhamid Elaissari, 3 and Asim.ur. Rehman 1,4 Received 10 November 2017; accepted 16 March 2018 Abstract. Biodegradable materials are extensively employed to design nanocarriers that mimic extracellular environment in arthritis. The aim of this study was to formulate and characterize biocompatible, biodegradable ketoprofen-loaded chitosan-chondroitin sulfate (CHS-CS) nanoparticles with natural ingredients for transdermal applications. Polymers used in the design of nanocarriers are biodegradable and produce synergistic anti-inflammatory effect for the treatment of arthritis. For transdermal application, argan oil-based emulgel is utilized to impart viscosity to the formulation. Furthermore, naturally occurring argan oil synergizes anti-inflammatory effect of formulation and promotes skin penetration. CHS and CS form nanoparticles by polyelectrolyte complex formation or complex coacervation at pH 5.0. These particles were loaded into argan oil-based emulgel. Employing this method, nanoparticles were formulated with particle size in the range of 300–500 nm. These nanocarriers entrapped ketoprofen and showed more than 76% encapsulation efficiency and 77% release of the ketoprofen at pH 7.4 within 72 h. Drug releases from CHS-CS nanoparticles by mechanism of simple diffusion. Nanoparticle-loaded argan oil emulgel significantly enhanced skin penetration of ketoprofen as compared to marketed gel (p < 0.05). Nanocarriers prepared successfully delivered drug through transdermal route using natural ingredients. KEY WORDS: arthritis; biocompatible; chitosan; chondroitin sulfate; transdermal drug delivery system. INTRODUCTION Arthritis is known as one of the most disabling diseases worldwide, and patients not only suffer from devastating effects of the disease but also have to bear bewildering array of systemic adverse effects allied with therapeutic moieties (1). Strategies designed to fabricate drug delivery carriers for arthritis management predominantly emphasize on targeted drug delivery system (2). Transdermal drug delivery systems (TDDS) are aimed to deliver drug through skin into the systemic circulation. Potential advantages that make trans- dermal route as a suitable alternative in chronic therapy include controlled peak plasma concentrations, reduced systemic side effects and bypass first pass effect, and prevent enzymatic breakdown of drug and damage to gastrointestinal (GI) tract (3). Different techniques are utilized to enhance skin perme- ability for drugs with the objective to disrupt skin barrier by interactions with skin lipids including chemical penetration enhancers, physical penetration enhancing techniques, and nanocarriers (4). Every technique is associated with some pros and cons. Still, nanocarriers are extensively used to enhance skin permeability owing to their small size that allows skin penetration without disrupting its functional integrity (5). Most commonly utilized nanocarriers for TDDS include nanoparticles which may be metallic, polymeric, lipid- based, nanovesicles (liposomes, ethosomes, niosomes, and transferosomes), and dendrimers (6,7). The success of trans- dermal delivery of nanoparticles depends on the ability of these carriers to pass through the skin layers and release encapsulated drug into the dermis for systemic absorption (8). Although it is well recognized that nanocarriers can breach skin barrier easily than larger particles but most of the environmental foreign particles like bacteria and viruses are unable to pass through this skin barrier owing to the existence of defensive immunological cells in layers of the skin (9). Thus, biomimetic nanoparticles are needed for crossing this 1 Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan. 2 Department of Pharmacy, University of Swabi, Swabi, Pakistan. 3 Univ Lyon, University Claude Bernard Lyon-1, CNRS, LAGEP- UMR 5007, F-69622, Lyon, France. 4 To whom correspondence should be addressed. (e–mail: arehman@qau.edu.pk) AAPS PharmSciTech ( # 2018) DOI: 10.1208/s12249-018-0997-0 1530-9932/18/0000-0001/0 # 2018 American Association of Pharmaceutical Scientists