Fabrication of chlorambucil loaded graphene- oxide nanocarrier and its application for improved antitumor activity

Biomed Pharmacother. 2020 Sep:129:110443. doi: 10.1016/j.biopha.2020.110443. Epub 2020 Jun 24.

Abstract

The present study aims at designing a biodegradable and biocompatible nanocarrier using gelatin and reduced graphene oxide nanosheets functionalized with folic acid, for release of chlorambucil drug in controlled manner and achieving high loading efficiency. From scanning electron microscopic studies small pore like structure with rough and thick morphology on the plane of graphene oxide is clearly visible indicating high loading of drug. Further, Drug loading and encapsulation efficiency, in vitro release studies of the drug from the nanocarrier at different concentrations of reduced graphene oxide, different pH were studied. The mean particle size, entrapment efficiency (%) of optimized folic acid functionalized gelatin-graphene oxide formulation was observed to be 300 nm and 56% respectively. From the release studies it is clear that, after 24 h the release rate of the drug was found to be higher at acidic conditions compared to neutral conditions. It was found that 62.1% and 82% of the total bound drug was released from the nanocarrier at pH 5.4 and pH 1.2 respectively. Besides, under neutral conditions (pH 7.4), 43.7% of the total bound drug was released from the nanocarrier in the first 24 h. The % cell viability of free drug, drug loaded nanocomposites against human cervical adenocarcinoma cell line was found to be 11.7% and 28% respectively at the dose of 500 μg mL-1 after 24 h. IC50 values also manifest the significantly lower cytotoxicity of drug loaded nanocarrier (IC50 = 125.9 μg/mL) as compared to free-drug (IC50 = 86 μg/mL). For FAGGO, CLB and CLB-FAGGO the values of mean ± std. deviation were found to be 71.80 ± 6.66; 48.71 ± 23.15; 55.48 ± 19.65 respectively. The unique properties exhibited by biodegradable polymer like gelatin and carbon based materials such as graphene offers an excellent applications in biomedical field.

Keywords: Chlorambucil drug; Folic acid; Graphene oxide; Targeted drug delivery; Therapeutic effect.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / pathology
  • Antineoplastic Agents, Alkylating / chemistry
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chlorambucil / chemistry
  • Chlorambucil / pharmacology*
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Female
  • Folic Acid / chemistry
  • Gelatin / chemistry
  • Graphite / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Inhibitory Concentration 50
  • Kinetics
  • Nanoparticles*
  • Uterine Cervical Neoplasms / drug therapy*
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents, Alkylating
  • Delayed-Action Preparations
  • Drug Carriers
  • graphene oxide
  • Chlorambucil
  • Graphite
  • Gelatin
  • Folic Acid