PLGA-PEG-RA-based polymeric micelles for tumor targeted delivery of irinotecan

Abstract

To develop an effective therapeutic treatment, the potential of poly (lactic-co-glycolic acid)-polyethylene glycol-retinoic acid (PLGA-PEG-RA) polymeric micelles for targeted delivery of irinotecan to hepatocellular carcinoma (HepG2) and colorectal cancer cell lines (HT-29) was evaluated. PLGA-PEG-RA was synthesized by amide reaction of PLGA with NH2–PEG–NH₂ and then PLGA-PEG-NH₂ with RA and confirmed by FTIR and ¹H NMR spectroscopy. Irinotecan-loaded nanomicelles were prepared using thin-film hydration method and the impact of various formulation variables on their particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), and mean release time (MRT) were assessed using a Taguchi design. TEM was used to observe morphology of the nanomicelles and the CMC was determined by fluorescence spectroscopy. Adopted PLGA-PEG-RA nanomicelle exhibited PS of 160 ± 9.13 nm, PDI of 0.20 ± 0.05, ZP of −24.9 ± 4.03 mV, EE of 83.9 ± 3.61%, MRT of 3.28 ± 0.35 h, and CMC value of 25.7 μg/mL. Cytotoxicity of the targeted nanomicelles on HepG2 and HT-29 cell lines was significantly higher than that of non-targeted nanomicelles and the free drug. These results suggest that PLGA-PEG-RA nanomicelles could be an efficient delivery system of irinotecan for targeted therapy of colorectal cancer and hepatocellular carcinoma.

Keywords:

• Irinotecan
• PLGA
• PEG
• retinoic acid
• micelle
• HepG2
• HT-29

Disclosure statement

We wish to thank the Vice Chancellery of Isfahan University of Medical Sciences for financial support of this work. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

The content of this article is extracted from the Pharm.D thesis No. 391408 submitted by Parnian Maghzi, which was financially supported by the Research Department of Isfahan University of Medical Sciences, Isfahan, I.R. Iran.