Development and Characterization of Propylene Glycol Alginate –Folic Acid Conjugate Based Micelles Containing Erlotinib

Abstract

Introduction: Erlotinib (ERL) is an epidermal growth factor receptor type (HER-1) tyrosine kinase inhibitor, which has been approved for the treatment of metastatic advanced non-small cell lung (NSCLC) and pancreatic cancer.

Objectives: The present work aims to synthesize the conjugate of propylene glycol alginate-folic acid (PGA-FA) and employ it to prepare ERL-loaded micelles, using the thin film hydration method which is further evaluated in vitro and in vivo.

Methods: The conjugate was synthesized via a reaction of the carboxyl groups of folate with the amine groups of PGA and catalyzed by EDC (1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide) as an amide coupling agent. The prepared conjugates were characterized by 1H NMR, DSC, XRD, SEM, and TEM. In vitro, the drug release profile was evaluated for ERL-loaded micelles using dialysis bag methods.

Results: The results showed that the drug was entrapped successfully within the hydrophobic core of the micelles. In the study, ERL-loaded micelles showed higher Cmax (76.6754 ng/ml for IV) than free ERL (39.4079 ng/ml and 44.7574 ng/ml through the oral route and Intramuscular route, respectively) and higher AUC0-24 (321.78797 ng/ml.h) than free drug (266.78127 ng/ml.h and 347.49328 for oral and IV respectively). 

Conclusions: The present investigation revealed that ERL-functionalized micelles might be promising for delivering anti-cancer agents and improving their therapeutic efficacy.