Synthesis, Characterization and Application of Functionalized Graphene Quantum Dots Incorporated Micro/Nano Poly (N, N–Diethyl Acrylamide) Hydrogel as Drug Delivery System

Abstract

Cancer has emanated as a daunting menace to human-kind even though medicine, science, and technology has reached its zenith. Subsequent scarcity in the revelation of new drugs, the exigency of salvaging formerly discovered toxic drugs such as doxorubicin has emerged. The invention of the drug carrier has made drug delivery imminent which is ascribable to its characteristic traits of specific targeting, effective response to stimuli and biocompatibility. Temperature responsive polymers hold great promise in biological applications as they respond to change in environmental temperature to produce the desired effect like controlled drug delivery. The objective of this work is to develop macro and nano forms of temperature responsive hydrogels intended for drug delivery applications. This work deals with the synthesis and optimization of macroporous temperature responsive hydrogel poly (N, N-diethyl acrylamide) (PDEA) was via free-radical-polymerization. The optimized hydrogel was achieved by evaluating the swelling characteristics, physical stability, and mechanical strength; through altering the components namely concentration of N, N-diethyl acrylamide (monomer), ammonium peroxodisulfate (initiator), N, N’-methyl bisacrylamide (cross-linker) and N, N, N’, N’-tetramethyl ethylenediamine (accelerator). LCST of the polymeric carrier has been modified by the addition of graphene quantum dots (GQDs). Inverse emulsion polymerization method was used to synthesize PDEA and GQDs incorporated PDEA nanohydrogels. Operating parameters like stirrer speed, water/oil ratio, and surfactant concentration were varied to optimize the conditions for the production of nanohydrogels. From the temperature responsive studies, it has been observed that the equilibrium swelling ratio (ESR) and reswelling kinetics of the hydrogel significantly increased as the GQDs content was varied. The cancer drug Doxorubicin (DOX) (a hydroxyl derivative of anthracycline) release behavior was studied at above and below the LCST temperature. The particle size of pure PDEA nanohydrogel was in the range of 47 to 59.5 nm, and graphene quantum dots incorporated nanohydrogels was in the range of 68.1 to 87.5 nm. It was found that the DOX release from the DOX-loaded macro/nanohydrogels was significantly improved when the surrounding temperature of the release media was increased near to physiological temperature. The LCST of theii synthesized hydrogels has been found to be in the range of 28-42 °C. The hydrogels cumulative release profile at different surrounding temperature was fitted in different kinetic model equations and delineated a non-Fickian diffusion release mechanism for macrogels and Fickian diffusion release mechanism for nanohydrogels. The hydrogel was assessed for its cytotoxicity in B16F10 cells by MTT assay. In-vivo studies were done to study the lung metastasis using melanoma cancer, and the results showed a rational favorable prognosis which was confirmed by evaluating hematological parameters and the non-immunogenic nature of nanohydrogel through cytokine assay. Comprehensively, the results suggested that GQDs incorporated poly (N, N-diethyl acrylamide) hydrogels have potential application as a intelligent drug carrier for melanoma cancer.