A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery

Hindawi Publishing Corporation Journal of Nanomaterials Volume 2016, Article ID 9816461, 8 pages http://dx.doi.org/10.1155/2016/9816461 Research Article A pH-Sensitive Injectable Nanoparticle Composite Hydrogel for Anticancer Drug Delivery Yuanfeng Ye and Xiaohong Hu School of Material Engineering, Jinling Institute of Technology, Nanjing 211169, China Correspondence should be addressed to Xiaohong Hu; Received 26 November 2015; Accepted 24 January 2016 Academic Editor: Ester Vazquez Copyright © 2016 Y. Ye and X. Hu. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. According to previous reports, low pH-triggered nanoparticles were considered to be excellent carriers for anticancer drug delivery, for the reason that they could trigger encapsulated drug release at mild acid environment of tumor. Herein, an acidsensitive 𝛽-cyclodextrin derivative, namely, acetalated-𝛽-cyclodextrin (Ac-𝛽-CD), was synthesized by acetonation and fabricated to nanoparticles through single oil-in-water (o/w) emulsion technique. At the same time, camptothecin (CPT), a hydrophobic anticancer drug, was encapsulated into Ac-𝛽-CD nanoparticles in the process of nanoparticle fabrication. Formed nanoparticles exhibited nearly spherical structure with diameter of 209 ± 40 nm. The drug release behavior of nanoparticles displayed pH dependent changes due to hydrolysis of Ac-𝛽-CD. In order to overcome the disadvantages of nanoparticle and broaden its application, injectable hydrogels with Ac-𝛽-CD nanoparticles were designed and prepared by simple mixture of nanoparticles solution and graphene oxide (GO) solution in this work. The injectable property was confirmed by short gelation time and good mobility of two precursors. Hydrogels were characterized by dynamic mechanical test and SEM, which also reflected some structural features. Moreover, all hydrogels underwent a reversible sol-gel transition in alkaline environment. Finally, the results of in vitro drug release profile indicated that hydrogel could control drug release or bind drug inside depending on the pH value of released medium. 1. Introduction Given the fact that the pH value in normal tissue is about 7.4, the pH value in infectious and inflammatory sites is about 6.5, and the pH values in tumor tissue are lower than 6.5, low pH-triggered nanoparticles have received much concern in anticancer drug delivery system, aiming at achieving better efficacy and avoiding side effects [1–3]. In view of good processability and degradation, synthesized ester polymers or copolymers were primary materials for low pH-triggered nanoparticles [4, 5]. But as for natural cyclodextrins (CDs), proven effective materials to control drug release, they were seldom fabricated to be low pH-triggered nanoparticles alone on account of their poor processability and no pH-sensitive property. Recently, the emerging of acetalated CDs (Ac-CDs) changed this condition [6]. Ac-CD could be prepared to be low pH-triggered nanoparticles by microemulsion method [1–3, 7–9]. As far as the application of nanoparticles was concerned, they were mainly used as targeted anticancer drug carrier, which meant that nanoparticles must get through all tiny blood capillary before they reached the targeted site [1– 3]. However, the size of Ac-CD nanoparticles was not small enough to get through the tiniest blood capillary according to previous report. Furthermore, they as 1D material were hardly fixed to targeted sites for some period even if they were injected to that site. Besides the above-mentioned disadvantages, another could not be neglected; that is, tedious centrifugal separation process in microemulsion method not only deteriorated the output of nanoparticle but also resulted in some broken nanoparticles with lost drug. Therefore, it has great significance to establish a 3D material using Ac-CD nanoparticle solution without getting rid of emulsifier, aimed at anticancer drug delivery. Hydrogel, the semisolid material, which is composed of hydrophilic polymer network and enormous embedded water, has been intensively investigated. The solid-liquid structure endows hydrogel with a number of flexible properties like adjustable swelling property, stimuli-responsive 2 ability, and biocompatibility [10–13]. Besides these merits, injectable hydrogel has advantages of minimally invasive operation and filling irregular defects of tissues [12–14]. In this sense, injectable hydrogel is increasingly attractive in the field of tissue engineering and drug delivery [10–14]. The driving force of injectable hydrogel includes chemical crosslinking, polymerization in situ, electrostatic interaction, and host-guest interaction [14]. Based on the facts that chemical methods have some disadvantages of toxicity, severe reaction condition, physical methods are interesting approaches for injectable hydrogel investigation, though the physical driving force is often not strong enough to support hydrogel for long-term use. Herein, we attempted to design an injectable hydrogel based on Ac-CD nanoparticle solution using a physical driving force for the hydrophobic drug delivery. Recently, it was reported that graphene oxide (GO) and polyvinyl alcohol (PVA) could self-assemble into supermolecular hydrogel in aqueous solution due to the strong interfacial interaction between these two components [15– 18]. GO, a member of graphene family, also possessed excellent properties of graphene like mechanical properties, large surface area, low coefficient of thermal expansion, and very high aspect ratio [13, 19]. When it came to graphene family, the newly interesting materials displayed great potential in the drug delivery field, especially for poorly soluble drug delivery, on account of its typical two-dimensional 𝜋conjugated structure [13]. For this reason, a number of hydrogels and nanocarriers made by graphene family material became new favorites of researchers [20–22]. Since PVA was a main emulsifier in the process of nanoparticle preparation, injectable hydrogels were assembled by supermolecular interaction between GO and PVA in this work. Moreover, the properties of both low pH-triggered nanoparticles and injectable hydrogel were investigated in the work. Camptothecin (CPT), a hydrophobic anticancer drug, has limited curative effect on account of slight solubility in aqueous environment, which results in intensive research on CPT modifications to improve its solubility in aqueous solution [8, 13, 23]. Among these modifications, the addition of solubilizers like CDs and their derivatives is an effective and efficient method [13, 23]. So it is inferred that Ac𝛽-CD, a CD derivative, was also a kind of ideal carrier material. Hence, CPT was chosen as a model drug and encapsulated in Ac-𝛽-CD nanoparticle during the fabrication of nanoparticles in the work. (...truncated)