Niosome encapsulated fuorouracil as drug delivery system to basal- cell skin cancer Saiavash Hosseinpour Chermahini 1,2 , Rahim Bahri Najafi 1 Chermahini SH, Najafi RB. Niosome encapsulated fluorouracil as drug delivery system to basal-cell skin cancer. J Nanosci Nanomed 2019;3(1):1-4. Basal-cell skin cancer is one of the most common diseases in countries which are in contact with sunshine more. Hence, it can be considered as a sophisticated problem that researcher are faced to that. Although, a few drugs such as fluorouracil have been suggested and accepted for this purpose, but still it’s necessary to design a system to deliver this drug to deep part of skin. Hence, with this system the drug can pass easily through the Stratum Corneum (SC) and reach to desire site of action. The aim of this research is to assemble and evaluate a nano-carrier to carry fluorouracil to desired site of action without any side effects as enhanced permeability system. For this purpose, after encapsulation of noisome as a vehicle the size and stability of that, was measured by Malvern Mastersizer. The result showed that the size was between 200 to 400 nm and the zeta potential was about 60 that is good stability. Key Words: Niosome; Vehicle; Enhanced permeability; Fluorouracil; Basal-cell skin cancer INTRODUCTION With the growth of nanotechnology, nanomedicine is developed for various application of treatment through delivery of the drug to the desired site of action. To this regards using a system based on nano size concept is well recognized [1-3]. As a matter of fact, this idea has derived from the nature that most of the activities in the living organism like human bodies are based on the design of bioactive systems with a concept of polymeric drugs delivery. Some well-known bioactive compounds for these systems can be counted as heparin, insulin, growth hormone and others which are designed and fabricated in our body within an accurate architecture [4]. The design and composition of cells and the extracellular matrix in the human organism are created to have interactions with nano molecules through specific properties [5,6]. Niosome as a complete system can be a suitable vehicle for delivery of drug to desire cells such as cancer cells or tumor. This process is possible due to the amphiphilic nature of niosome’s structure, containing both hydrophobic and hydrophilic domains [7-9]. The structural characteristics of niosome have several advantages to improve the effectiveness and safety of cancer therapy in case of clinical use [10-13]. For instance, the encapsulation of drug in the core of this system improves their aqueous diffusion and transport, as well as bioavailability and decreasing their toxic side effects [14,15]. This system also allows the drugs to protect from degradation and produces their controlled release to the cancer cell due to the Enhanced Permeability and Retention (EPR) effect [16-18]. On the other hand, advances in engineering suggests a wide range of possibilities to control the most influential properties of the polymeric assemblies, such as the particle size, stability or loading capacity [7,19]. In fact affinity to receptors over expressed in skin cancer cells, are the most important parameters to control and enhance mechanism of incorporation bioactive nano particle systems which are endocytosis or pinocytosis. The application of this system brings novel and advanced possibilities including the lowering toxicity, without a noticeable decrease of the drug activity that can be considered the first generation of nanomedicine. It includes polymers with characteristics biological activity, that form multicomponent designed for intracellular delivery of drug [20,21]. The self-assembled nano particle contains the Fluorouracil (5-FU) in the core and a sensitizer located in shell layer targeting ligand for interaction and selective linking to the cytoplasmatic membrane [22]. The design of this system protects the fluorouracil until the cytoplasmatic membrane is reached [23,24].Hence, skin drug delivery represents a promising approach that aims to address the disease from the molecular point of view. This type of treatment is based on modified or normal functioning of drug that is delivered into the cell nucleus to prevent DNA replication. Fluorouracil (5-FU) acts in several ways, but principally as a Thymidylate Synthase (TS) inhibitor. Interrupting the action of this enzyme blocks synthesis of the pyrimidine thymidine, which is a nucleoside required for DNA replication. Thymidylate synthase methylates deoxyuridinemonophosphate (dUMP) to form thymidine monophosphate. Administration of fluorouracil causes a scarcity in dTMP, so rapidly dividing cancerous cells undergo cell death via thymineless death. Calcium folinate provides an exogenous source of reduced folinates and hence, stabilises the 5-FU-TS complex, hence enhancing 5-FU's cytotoxicity [25]. It is necessary the use of capable vehicle to deliver efficiently the drug inside the cells that are mainly based on cationic polymers and helper lipids [26]. Niosomes are drug carrier systems similar to liposomes with a bilayer structure, where the phospholipids of the liposomes have been substituted by non-ionic surfactants. Compared to liposomes, niosomes show some significant advantages, such as low cost and high chemical and storage stabilities. Even though the application of niosomes in skin drug delivery has been poorly studied, some optimistic results have been recently reported in the literature that highlights the satisfactory properties of niosomes for drug delivery purposes [27,28]. Niosome as a vehicle is commonly based on non-ionic surfactants, cationic polymers and lipids. Over the years, several researchers have studied these components and their effect on the niosome formulations. Such studies have shown that non-ionic surfactants make niosome formulations stable, and prevent the aggregates of the particles [29,30]. Cationic lipids handle the interaction with the negatively charged fluorouracil and its condensation to form nio-flu by electrostatic interactions [31]. Additionally, it has been observed that cationic lipid chemical structures influence on the niosomes charge, toxicity, biodegradability, and transfection efficiencies [32,33]. Regarding to helper lipids, it has been described that they are responsible for enhancing the physicochemical properties of the emulsion and the improvement of drug delivery [34,35]. However, the mechanisms that involve these improvements in cationic niosome formulations for drug delivery applications have not been completely surveyed, and more detailed studies are required. The final impact on fluorouracil expression, among many other factors, clearly depends on the cell to be transfected and on the capacity of the vehicle to enter the cell and the posterior pathway employed to deliver its cargo into the nucleus [36]. Different endocytic routes can mediate the cellular uptake RESEARCH ARTICLE 1 Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, Iran, 2 The University of Georgia, ostava St. * Correspondence : Siavash Hosseinpour Chermahini, Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, Iran. Telephone +967 739899435, e-mail S.Chermahini@ug.edu.ge Received: September 16, 2018, Accepted: April 16, 2019, Published: April 21, 2019 This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC) (http:// creativecommons.org/licenses/by-nc/4.0/), which permits reuse, distribution and reproduction of the article, provided that the original work is properly cited and the reuse is restricted to noncommercial purposes. For commercial reuse, contact reprints@pulsus.com J Nanosci Nanomed Vol.3 No.1 April-2019 1 77a, 0171 Tbilisi, Georgia K