Carbon Dot Cross-Linked Gelatin Nanocomposite Hydrogel for pH-Sensing and pH-Responsive Drug Delivery

Abstract

Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the in vitro drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.

Carbon Dots as an Emergent Class of Antimicrobial Agents

“…Many bactericidal applications of CD-composites rely on combining the photodynamic ROS production of the CDs with the antibiotic activity of a transition metal-based nanoparticle [ 111 ], often containing Ag [ 84 ], Cu [ 112 , 113 , 114 ], Zn [ 115 , 116 , 117 ], or Ti [ 118 ] oxides cores, among others. Moreover, CDs have been embedded within polymeric structures, including hydrogels and polymers of different natures, ranging from chitosan [ 119 , 120 ] to DNA [ 121 ], cellulose [ 122 ], gelatin [ 123 ], polyurethane [ 124 ], or poly lactic-co-glycolic acid nanoparticle [ 125 ] matrices. These composites have found ample antibacterial applications (such as in water treatment [ 126 , 127 , 128 , 129 ] and the surface coating field [ 130 , 131 , 132 ]).…”

Shaping Macromolecules for Sensing Applications—From Polymer Hydrogels to Foldamers

“…Polymeric materials used for sensors are divided into natural hydrogels, derived from natural polymers, e.g., proteins (collagen [ 76 , 80 , 83 ], elastin [ 84 , 85 ], gelatin [ 86 , 87 , 88 ], albumin [ 29 , 89 ]), polysaccharides (hyaluronic acid [ 90 ], alginate [ 91 , 92 , 93 , 94 , 95 ], chitosan [ 82 , 96 , 97 , 98 , 99 , 100 , 101 ], cellulose [ 74 ]), and synthetic hydrogels [ 39 , 102 , 103 , 104 , 105 , 106 ], based on laboratory-made polymers. Hydrogels in sensing applications are often used as a hybrid material, blend of polymers or in composition with inorganic materials, e.g., graphene, graphene oxide, or silica [ 31 ].…”

“…For instance, carbon additives provide material conductivity that enables the application of amperometric detection techniques. Hydrogels can be used in diverse forms, suitable for final applications, e.g., hydrogel films, self-standing substrate, or nano and microparticles [ 55 , 88 , 92 , 108 ].…”

“…The classification of the natural hydrogels includes two main groups, based on their derivation. The first group is represented by protein-based materials [ 76 , 80 , 83 , 84 , 85 , 86 , 87 , 88 , 89 ] which include collagen, elastin, fibrin, gelatin, and skin fibroin. The second group is constituted of hydrogels derived from polysaccharides [ 74 , 82 , 90 , 91 , 92 , 93 , 96 , 97 , 98 ] such as glycosaminoglycans, alginate and chitosan.…”

Magnetoresponsive biocomposite hydrogels comprising gelatin and valine based magnetic ionic liquid surfactant as controlled release nanocarrier for drug delivery

“…Gelatin gels although very useful, have certain inherent limitations like lack of controllability, actuation, and quick-response properties. [18][19][20] In new existence, magnetic biomaterial scaffolds are new active promising materials made up of biopolymers and magnetic nanoparticles and show magneto-responsive behavior. 21,22 Polymer hydrogels containing magnetic particles are stimuliresponsive gels, their viscoelastic properties can be controlled by applying magnetic fields.…”