Co-delivery of norfloxacin and tenoxicam in Ag-TiO 2 /poly(lactic acid) nanohybrid Nehal Salahuddin a, ⁎, Mohamed Gaber a , Sahar Elneanaey a , Michael R. Snowdon b , Mohamed A. Abdelwahab a, ⁎ a Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt b Department of Plant Agriculture, Crop Science Building, University of Guelph, 117 Reynolds Walk, Guelph, Ontario N1G 1Y4, Canada abstract article info Article history: Received 6 November 2020 Received in revised form 4 March 2021 Accepted 6 March 2021 Available online 08 March 2021 Keywords: Targeted delivery Norfloxacin Tenoxicam Nanohybrids A nanohybrid formulation of silver‑titanium dioxide nanoparticles/poly(lactic acid) (Ag-TiO 2 /PLA) was designed for Norfloxacin/Tenoxicam (NOR/TENO) targeted delivery to maximize the bioavailability and minimize the side effects of the drugs. Ag-TiO 2 nanoparticles were prepared via Stober method. NOR, TENO and a mixture of NOR/ TENO (NT) were loaded onto Ag-TiO 2 nanoparticles and coated by PLA via solution casting. The physical interac- tion between the drugs and carrier was confirmed by Fourier-transform infrared (FTIR) analysis. X-ray diffraction (XRD) demonstrated that Ag-TiO 2 consists of a cubic phase of Ag with two phases of TiO 2 (anatase and brookite). Ag nanoparticle fine spots coated with TiO 2 were collected to form spheres averaging at 100 nm in size. In-vitro release behavior of drugs was studied at different pH (5.4, 7.4) and the release of drug from NT/Ag-TiO 2 /PLA was faster at pH 7.4. Gram-positive and Gram-negative bacteria were used to investigate antibacterial properties of the nanohybrid. Cytotoxicity of the nanohybrid using an MTT assay was studied against different tumor and normal cell lines. It was found that NT/Ag-TiO 2 /PLA has an excellent cytotoxic effect against various bacterial cells and tumor cell lines. In addition, antioxidant properties of the nanohybrids were tested using ABTS method and the nanohybrid showed moderate antioxidant activity. © 2021 Published by Elsevier B.V. 1. Introduction Significant attention has been given to nanoparticles in the field of biomedical science for bioimaging, controlled drug release, targeted drug delivery, cell labelling and tissue engineering applications [1]. Sil- ver (Ag) nanoparticles have an excellent antimicrobial activity through interaction with the main component of a microbial cell (cell wall and plasma membrane), DNA, proteins and enzymes [2–4]. Ag nanoparticles display a cytotoxic effect on tumor cells as they aid in the transportation of drugs into the tumor cells and obstruct the metabolism of tumor pro- liferation [5]. However, Ag nanoparticles bind rapidly to environmental factors and become inactive, damage tissues such as the liver or lung and penetrate the blood-brain barrier [6]. TiO 2 nanoparticles were dem- onstrated to have biocompatibility, limited toxicity, photocatalytic ac- tivity, antibacterial activity, anticancer activity [7] and can release the drug in a pH-dependent manner into the cells [8]. However, TiO 2 nano- particles have some shortcomings as in the rapid recombination rate for the photoinduced electron/hole pair, agglomeration of particles [9] and large bandgap with excitation by ultraviolet light [10]. Ag-TiO 2 nanopar- ticles have been studied because of the dual function of Ag and TiO 2 sites. First, Ag nanoparticles act as an electron scavenging center to sep- arate e - /h + pairs because its Fermi level is below the conduction band of TiO 2 . Second, Ag nanoparticles can create the surface plasmon reso- nance (SPR) effect of TiO 2 nanoparticles, thus enhancing the photocata- lytic activity of TiO 2 nanoparticles in the visible region [11]. Therefore, the reactive oxygen species (ROS) generating potential of Ag-TiO 2 nano- particles can be used in the treatment of cancer without using light. Ma- nipulating the intracellular ROS level by redox modulators can selectively harm cancer cells without affecting normal cells [12]. Targeted drug delivery system (TDDS) is a unique option where the drug is targeted only to a specific site or sites. TDDS improves the drug's therapeutic index by facilitating the drug to reach the action site from the administration site; protecting the drug from degradation by envi- ronmental factors within the body such as enzymes, pH, etc.; preventing toxicity of the drug on normal cells; facilitating administration of lower doses to achieve therapeutic benefits and releasing the active ingredi- ents of drugs in or around the target site to achieve cellular concentra- tions [13]. Poly(lactic acid) (PLA) has received significant attention as a poten- tial candidate for many pharmaceutical and medical applications due to its biodegradability, biocompatibility, bioadsorbability and nontoxic characteristics [14]. PLA can be degraded into nontoxic materials at different pH solutions and undergo chain scission by hydrolysis to mo- nomeric units of lactic acid, water and carbon dioxide in vivo, even in International Journal of Biological Macromolecules 180 (2021) 771–781 ⁎ Corresponding authors. E-mail addresses: nehal.attaf@science.tanta.edu.eg (N. Salahuddin), mohamed.abdelwahab@science.tanta.edu.eg (M.A. Abdelwahab). https://doi.org/10.1016/j.ijbiomac.2021.03.033 0141-8130/© 2021 Published by Elsevier B.V. Contents lists available at ScienceDirect International Journal of Biological Macromolecules journal homepage: http://www.elsevier.com/locate/ijbiomac