Contents lists available at ScienceDirect Applied Surface Science journal homepage: www.elsevier.com/locate/apsusc Controllable delivery system: A temperature and pH-responsive injectable hydrogel from succinylated chitosan Jae Seo Lee a , Haram Nah a , Ho-Jin Moon b , Sang Jin Lee b , Dong Nyoung Heo b,1, ⁎ , Il Keun Kwon b, ⁎ ,1 a Department of Dentistry, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea b Department of Dental Materials, School of Dentistry, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Republic of Korea ARTICLE INFO Keywords: Natural based hydrogel Injectable ability Drug carrier Controllable drug release ABSTRACT Drug-loaded hydrogel-based controllable drug delivery systems (DDS) have received considerable attention since they may overcome the drawbacks of conventional drug administration. The desirable hydrogels can be injected in any part of the body and are easily-available. To develop DDS, a succinylated chitosan (SCS)-based hydrogel was manufactured using facile and water-based conditions. This ideal and ecofriendly hydrogel showed rapid gelation and efcient release of gold nanoparticles (GNP) as representative small particles and drug substitutes. Moreover, the SCS hydrogel showed outstanding GNP release at low pH, with 100% degradation after a week at a pH of 5.5. Additionally, the drug release rate of SCS hydrogel could be controlled by adjusting succinylation and temperature. The SCS hydrogel exhibited good biocompatibility for applications in DDS. On the basis of these advantages, the SCS hydrogel can be used as a drug-loaded vehicle, which can be released at the appro- priate time (important for cancer and infammation treatments) and injected at the appropriate site. 1. Introduction Uncontrolled drug release is a major cause of mortality in severe trauma. In particular, drug overdose produces toxic substances that interfere with metabolic processes, leading to serious liver damage and acute liver failure, and represents a major public health concern [1]. These adverse events can signifcantly reduce physical activity, increase the risk of complications, and compromise therapeutic efects [2,3]. Additionally, conventional drug administration is typically performed at high doses and through repeat cycles to obtain adequate therapeutic efect at the desired time. In this regard, controlled drug delivery sys- tems (DDS) are pivotal to reduce drug toxicity and enhance therapeutic efcacy [4]. To address the issues mentioned above, many researchers have started to focus on nanocarriers to deliver drugs at a predetermined time [5]. In current treatments, DDS are widely used with numerous diferent carriers, such as electrospinning fbers, micelles, and hydro- gels. However, there are some limitations in the use of electrospun nanofber scafolds for drug delivery, such as the immobilization of drugs in nanofbers and inhibition of release due to impeded water difusion into these materials [6,7]. Moreover, several properties limit the efciency of polymeric micelles, including insufcient drug loading capacity, binding, and cellular uptake [8]. To overcome these limitations, hydrogels are thought to be an outstanding choice for DDS in tissues and organs. Contrary to the other materials, hydrogels can encapsulate large quantities of drugs and ea- sily permeate water molecules and nutrients [9]. Furthermore, hydro- gels show ideal injectable properties at room temperature for clinical application. In crosslink systems, ionic crosslinking hydrogels are par- ticularly advantageous according to the temperature and pH conditions of the released drugs [10]. Moreover, mechanical properties of physi- cally crosslinked hydrogels are afected by temperature and pH. Chitosan (CS), a polysaccharide comprising repeating units of 1,4-a- L-rhamnose and a copolymer of β-(1,4)-2-acetamido-D-glucose and β- (1,4)-2-amino-D-glucose units, is of particular interest for ionic cross- linking [11]. It is prepared from a natural polymer and shows good biocompatibility, and it has, therefore, received much attention for potential applications as a drug carrier. However, it can be dissolved in acidic conditions to confer the polymer with a positive charge, and it can also form hydrogel membranes. To overcome these limitations, succinylation is the easiest and most efective method to improve water solubility and obtain new functional groups. To prepare a weakly crosslinked hydrogel for fast-release drugs, succinylated chitosan was ionically crosslinked with glucose-6-phosphate (G6P) to create a pH- sensitive hydrogel. G6P is a crosslinking agent as hydrophilic molecule that promotes cell growth. https://doi.org/10.1016/j.apsusc.2020.146812 Received 25 February 2020; Received in revised form 18 May 2020; Accepted 27 May 2020 ⁎ Corresponding authors. E-mail addresses: leejaeseo@khu.ac.kr (J.S. Lee), heodaeng@khu.ac.kr (D.N. Heo), kwoni@khu.ac.kr (I.K. Kwon). 1 These corresponding authors have made equal contributions to this work. Applied Surface Science 528 (2020) 146812 Available online 04 June 2020 0169-4332/ © 2020 Elsevier B.V. All rights reserved. T