Folic acid conjugated polymeric micelles loaded with a curcumin difluorinated analog for targeting cervical and ovarian cancers

Duy Luong; Prashant Kesharwani; Hashem O Alsaab; Samaresh Sau; Subhash Padhye; Fazlul H Sarkar; Arun K Iyer

doi:10.1016/j.colsurfb.2017.06.025

Folic acid conjugated polymeric micelles loaded with a curcumin difluorinated analog for targeting cervical and ovarian cancers

Colloids Surf B Biointerfaces. 2017 Sep 1:157:490-502. doi: 10.1016/j.colsurfb.2017.06.025. Epub 2017 Jun 21.

Authors

Duy Luong¹, Prashant Kesharwani², Hashem O Alsaab³, Samaresh Sau¹, Subhash Padhye⁴, Fazlul H Sarkar⁵, Arun K Iyer⁶

Affiliations

¹ Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA.
² Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
³ Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Department of Pharmaceutics and Pharmaceutical Technology, Taif University, Taif, 26571, Saudi Arabia.
⁴ Interdisciplinary Science & Technology Research Academy, Department of Chemistry, Abeda Inamdar College, University of Pune, Pune 411001, India.
⁵ Retired Distinguished Professor, Department of Pathology, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
⁶ Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, 259 Mack Ave, Wayne State University, Detroit, MI 48201, USA; Molecular Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University, School of Medicine, Detroit, MI, 48201, USA. Electronic address: arun.iyer@wayne.edu.

Abstract

The current study utilizes folic acid conjugated poly(styrene-co-maleic anhydride) block copolymer (FA-SMA) to enhance the solubility of a hydrophobic but very potent synthetic curcumin-difluorinated (CDF) analog and its targeted delivery to folate receptor-alpha overexpressing cancers. The nanomicelles showed high aqueous solubility. Importantly, the encapsulation of CDF in nanomicelles resulted in high photo-stability of the otherwise photo-labile drug. When the nanomicelles were tested in folate-receptor overexpressing ovarian and cervical cancer cells they exhibited high anticancer activity causing significant cell population to undergo apoptosis due to upregulation of tumor suppressor phosphatase and tensin homolog (PTEN) and inhibition of nuclear factor kappa-B (NFκB), which further confirmed the targeting ability and anticancer potentials of folate-targeted formulations.

Keywords: Cervical cancer; Curcumin difluorinated (CDF); Flavonoid analog; Folate receptor-alpha targeting; Folic acid; Ovarian cancer; Polymeric micelles; Targeted drug delivery.

MeSH terms

Apoptosis / drug effects
Cell Line, Tumor
Curcumin / chemistry*
Drug Delivery Systems / methods
Female
Folic Acid / chemistry*
Humans
Micelles
Ovarian Neoplasms*
Polymers / chemistry*
Uterine Cervical Neoplasms*

Substances

Micelles
Polymers
Folic Acid
Curcumin

Grants and funding

R21 CA179652/CA/NCI NIH HHS/United States