ABSTRACT
Purpose: Recombinant human nerve growth factor (rhNGF; cenegermin-bkbj, OXERVATE) is the first and only U.S. Food and Drug Administration-approved treatment for moderate to severe neurotrophic keratopathy. The aim of this study was to determine the feasibility of incorporating a version of rhNGF in a mucoadhesive hydrogel capable of sustained drug release to the ocular surface. Methods: Hydrogels loaded with rhNGF were synthesized by conjugating chitosan with azidobenzoic acid (Az-Ch), adding rhNGF, and exposing the solution to ultraviolet (UV) radiation to induce photocrosslinking. Az-Ch hydrogels were evaluated for physical properties and rhNGF release profiles. Cytocompatbility of Az-Ch was assessed using immortalized human corneal limbal epithelial (HCLE) cells. TF1 erythroleukemic cell proliferation and HCLE cell proliferation and migration were used to assess the bioactivity of rhNGF released from Az-Ch hydrogels. Results: Az-Ch formed hydrogels in <10 seconds of UV exposure and demonstrated high optical transparency (75-85 T%). Az-Ch hydrogels exhibited good cytocompatibility with no demonstratable effect on HCLE cell morphology or viability. rhNGF was released gradually over 24 hours from Az-Ch hydrogels and retained its ability to induce TF1 cell proliferation. No significant difference was observed between rhNGF released from Az-Ch and freshly prepared rhNGF solutions on HCLE cell proliferation or percent wound closure after 12 hours; however, both were significantly better than control (P < 0.01). Conclusions: rhNGF-loaded Az-Ch hydrogels exhibited favorable physical, optical, and drug-release properties, as well as retained drug bioactivity. This drug delivery system has the potential to be further developed for in vivo and translational clinical applications. Translational Relevance: Az-Ch hydrogels may be used to enhance rhNGF therapy in patients with NK.
Subject(s)
Cell Proliferation , Chitosan , Hydrogels , Nerve Growth Factor , Nerve Growth Factor/pharmacology , Nerve Growth Factor/chemistry , Nerve Growth Factor/administration & dosage , Humans , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogels/chemical synthesis , Cell Proliferation/drug effects , Cell Movement/drug effects , Ultraviolet Rays , Cross-Linking Reagents/chemistry , Limbus Corneae/drug effects , Limbus Corneae/cytology , Recombinant Proteins/chemistry , Drug Delivery Systems/methodsABSTRACT
Graphene, which is a unique 2D nanomaterials has received widespread attention for photothermal therapy (PTT) application. Here, we have designed the nanocomposite using polydopamine (PDA) functionalized reduced graphene oxide (rGO) nanosheets and bimetallic AuPd nanoparticles (NPs). The bimetallic AuPd nanoparticles decorated PDA functionalized rGO (AuPd-rGO/PDA) nanocomposite is synthesized by simple chemical reduction technique resulting in an average size of AuPd bimetallic nanostructure of 4.18 nm. The photothermal activity of the AuPd-rGO/PDA nanocomposite is explored under the irradiation of near infrared (NIR) laser sources of wavelength 915 nm. The temperature rises nearly 51 ± 3 °C within 3 min of irradiation NIR laser light resulting in the ablation of MDAMB-231 cancer cells up to concentration of 25 µg mL-1 of AuPd-rGO/PDA nanocomposite. This high performance of the ablation of cancer cells by photothermal therapy technique was facilitated using a low concentration of the nanocomposite by the synergistic effects of the bimetallic AuPd as well as rGO and PDA functionalization. The AuPd-rGO/PDA nanocomposite demonstrated the high biocompatibility towards normal healthy cell lines (L929) and exhibits survival efficiency of more than 85%. We also demonstrated the biocompatibility of the AuPd-rGO/PDA nanocomposite materials on the zebrafish embryos (Danio rerio). This work thus illustrates that the AuPd-rGO/PDA nanocomposite could behave as favourable nanoplatform for tumor therapeutics.
Subject(s)
Gold/chemistry , Gold/pharmacology , Graphite/chemistry , Metal Nanoparticles/chemistry , Palladium/chemistry , Palladium/pharmacology , Phototherapy/methods , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Humans , Indoles/chemistry , Nanomedicine , Oxidation-Reduction , Polymers/chemistry , TemperatureABSTRACT
Cervical cancer is the fourth largest cancer, affecting women across the globe. Rapid screening is of vital importance for diagnosis and treatment of the disease, especially in developing countries with high risk populations. In this paper, we report a simple, novel and rapid approach for qualitative screening of cervical cancer. A label-free colorimetric technique ("C-ColAur") involving the in situ formation of gold nanoparticles (Au NPs) in the presence of clinical samples is demonstrated. The as-formed Au NPs, owing to the sample composition produced a characteristic color that can be used for the qualitative detection of malignancy. We demonstrated the proof of principle using clinical samples (cervical fluid) collected from both cancer affected and healthy individuals. The results of the detection technique, "C-ColAur" when compared with those of the existing conventional diagnostic procedures (i.e. Pap smear or biopsy), showed 96.42% sensitivity. With the detection time less than a minute and with no/minimal sample processing requirements, the proposed technique shows great potential for point-of-care as well as clinical screening of cervical cancer.
