Common direct administration of therapeutic compounds is not anymore applicable owing to underlying limitations, like poor solubility, weak pharmacokinetics and non-specific targeting [1]. Thus, developing a novel controlled drug delivery system (DDS) is vital and crucial to lessen side effects and improve the restorative efficacy of drugs. In this regard, during the past decades, numerous kinds of nano-carriers have been suggested, including metal nanoparticles (NPs), liposomes, quantum dots and inorganic mesoporous materials [2–5]. However, most nano-carriers possess many drawbacks in biomedical applications. An ideal DDS should possess several initial requirements such as high loading efficiency, large surface area, low toxicity and bio-degradability [6, 7]. Metal-organic frameworks (MOFs) as a new category of highly porous tunable material, consisting of metal ions and organic bridging ligands [8–10]. MOFs have been fabricated via numerous synthetic procedures and employed for diverse applications, including catalysts, separations, optics and importantly the vast number of biomedical applications [11–13]. Nowadays, MOFs have received considerable interest in designing novel DDS and theragnostic platforms. The unique features of MOFs, involving tunable structure and size, ease of functionalization, low toxicity, and highly porous nature makes them encouraging carriers for different drugs/cargos [11, 14, 15]. For the first time, Ferey et.al presented the successful employment of MOFs in drug loading/ release fields [16]. Among various of MOFs, Zn-based MOFs showed a considerable capacity for the loading and release of numerous therapeutic agents [8, 17–18]. Nevertheless, many concerning challenges are still present in the development of novel Zn-MOFs for obtaining a smart nanocarrier in biomedical utilization, like biocompatibility of metal clusters and ligands, chemical stability of MOFs structure under acidic pH and targeted release of drugs [19–21]. The problem of zinc ions released from Zn-MOFs under an acidic environment leads to the production of reactive oxygen species (ROS) and subsequently destroys healthy tissues and cells [22]. To resolve the significant defects of MOFs for biomedical purposes, reduce side effects of drugs and controlled the application of metal ions, we suggested to develop biopolymer coated MOFs. A bio-polymer coating can improve the biocompatibility and durability of MOF-based nanocarriers [23]. Sodium alginate (SA), as a promising biodegradable non-synthetic polymer, consists of numerous hydroxyls and COOH functional groups; hence, it will be a suitable option for employ in the acidic biological condition owing to the loss of the alkaline hydrogens [24–26]. Therefore, it is used as a pH-responsive polymeric coating in oral DDS which can delay the rapid release of metal ions [27].
Zein (ZN) is a biocompatible and hydrophobic natural protein of corn origin and presents major advantages over many other synthetic polymers in DDS applications [28–30]. In comparison to other biopolymers, including gelatin, chitosan, albumin and soy protein, ZN has various peculiar benefits: a) ZN is categorized as one of the most biocompatible and safe excipients by the US Food and Drug Administration; b) it has high chemical stability towards digestive enzymes; and most importantly it is biologically biodegradable and non-toxic [29–32]. It was employed in numerous biomedical areas such as tissue engineering, drug/gene delivery, and antimicrobial films. Special interest in the potential application of ZN concentrated on its employment in controlled drug delivery platforms, like gels, films and encapsulation of anticancer agents with suitable biocompatibility and also showed good antibacterial activity [33–35]. Zhu et.al reported the successful fabrication of a novel DDS based on succinylated-ZN-ZIF-8 hybrid nanocomposite for controlled delivery of Indomethacin [36].
SA is the most abundant marine biopolymer in the world. SAs are a relatively broad family of polysaccharides found in brown seaweed that could be produced industrially. The main source of SA is found in the cell walls and intracellular space of brown seaweed and is also made by some bacteria such as Azotobacter and Pseudomonas. SA is the main form of SA and has properties such as hydrophilicity, biocompatibility, non-toxicity, and exceptional plasticity [24].
Here, we developed a novel SSZ loaded MOF/SA-ZN as a targeted drug nanocarrier for improvement of sulfasalazine’s bioavailability and controlled release. SSZ is a sulfa drug, used widely as a combined anti-inflammatory and anti-bacterial agent in the treatment of rheumatoid arthritis. Furthermore, it is a medication applied in the treatment of Crohn’s disease, ulcerative colitis and inflammatory bowel diseases [37–39]. By using this novel targeted DDS, it is expected that the sulfasalazine’s side effects minimized and enhances its therapeutic effectiveness.