Poly(N,N-diethyl acrylamide)/functionalized graphene quantum dots hydrogels loaded with doxorubicin as a nano-drug carrier for metastatic lung cancer in mice

Sushma Havanur; Inayat Batish; Sri Pragnya Cheruku; Karthik Gourishetti; JagadeeshBabu P E; Nitesh Kumar

doi:10.1016/j.msec.2019.110094

Poly(N,N-diethyl acrylamide)/functionalized graphene quantum dots hydrogels loaded with doxorubicin as a nano-drug carrier for metastatic lung cancer in mice

Mater Sci Eng C Mater Biol Appl. 2019 Dec:105:110094. doi: 10.1016/j.msec.2019.110094. Epub 2019 Aug 19.

Authors

Sushma Havanur¹, Inayat Batish¹, Sri Pragnya Cheruku², Karthik Gourishetti², JagadeeshBabu P E³, Nitesh Kumar²

Affiliations

¹ Department of Chemical Engineering, National Institute of Technology Karnataka, Surathkal, Mangalore, Karnataka, India.
² Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
³ Department of Chemical Engineering, National Institute of Technology Karnataka, Surathkal, Mangalore, Karnataka, India. Electronic address: jagadeesh_78@yahoo.com.

PMID: 31546441
DOI: 10.1016/j.msec.2019.110094

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 drug carrier has made drug delivery imminent which is ascribable to its characteristic traits of specific targeting, effective response to stimuli and biocompatibility. In this paper, the nanoscale polymeric drug carrier poly(N,N-diethyl acrylamide) nanohydrogel has been synthesized by inverse emulsion polymerization. Lower critical solution temperature of the polymeric carrier has been modified using graphene quantum. The particle size of pure 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. Doxorubicin (hydroxyl derivative of anthracycline) release behavior as a function of time and temperature was analyzed, and the Lower critical solution temperature of the synthesized nanohydrogels has been found to be in the range of 28-42 °C. Doxorubicin release characteristics have improved significantly as the surrounding temperature of the release media was increased near to physiological temperature. Further, the cumulative release profile was fitted in the different kinetic model and found to follow a Fickian diffusion release mechanism. The hydrogel was assessed for its cytotoxicity in B16F10 cells by MTT assay. In-vivo studies were done to study the lung metastasis by melanoma cancer and the results showed a rational favorable prognosis which was confirmed by evaluating hematological parameters and the non-immunogenic nature of nanohydrogel by cytokine assay. Comprehensively, the results suggested that poly(N,N-diethyl acrylamide) nanohydrogels have potential application as an intelligent drug carrier for melanoma cancer.

Keywords: Doxorubicin; Drug carrier; Graphene quantum dots; Melanoma; Nanohydrogel; Poly(N,N-diethyl acrylamide).

MeSH terms

Acrylamides* / chemistry
Acrylamides* / pharmacokinetics
Acrylamides* / pharmacology
Animals
Cell Line, Tumor
Doxorubicin* / pharmacokinetics
Doxorubicin* / pharmacology
Drug Carriers* / chemistry
Drug Carriers* / pharmacokinetics
Drug Carriers* / pharmacology
Graphite* / chemistry
Graphite* / pharmacokinetics
Graphite* / pharmacology
Hydrogels* / chemistry
Hydrogels* / pharmacokinetics
Hydrogels* / pharmacology
Lung Neoplasms* / drug therapy
Lung Neoplasms* / metabolism
Lung Neoplasms* / pathology
Mice
Neoplasm Metastasis
Neoplasms, Experimental* / drug therapy
Neoplasms, Experimental* / metabolism
Neoplasms, Experimental* / pathology
Quantum Dots* / chemistry
Quantum Dots* / therapeutic use

Substances

Acrylamides
Drug Carriers
Hydrogels
Graphite
Doxorubicin