Formulation of Genistein-HP β Cyclodextrin-Poloxamer 188 Ternary Inclusion Complex: Solubility to Cytotoxicity Assessment.

Ameeduzzafar Zafar,Faisal K Alkholifi,Sultan Alshehri,Alenazy Rawaf,Arafa Musa,Ali Alquraini,Abdullah S Alanazi,Omar Awad Alsaidan,Nabil K Alruwaili,Sadaf Jamal Gilani,Ehab M Mostafa,Khalid Saad Alharbi,Syed Sarim Imam

doi:10.3390/pharmaceutics13121997

Abstract

The current study was designed to prepare the inclusion complex Genistein (GS) using Hydroxypropyl β cyclodextrin (HP β CD) and poloxamer 188 (PL 188). The binary inclusion complex (GS BC) and ternary inclusion complex (GS TC) were developed by microwave irradiation technique and evaluated for a comparative dissolution study. Further, the samples were assessed for FTIR, DSC, XRD, and NMR for the confirmation of complex formation. Finally, antioxidant and antimicrobial studies and cytotoxicity studies on a breast cancer (MCF-7) cell line were conducted. The dissolution study result showed a marked increment in GS dissolution/release after incorporation in binary (GS: HP β CD, 1:1) and ternary (GS: HP β CD: PL 188; 1:1:0.5) inclusion complexes. Moreover, the ternary complex exhibited a significant enhancement (p < 0.05) in dissolution than did the binary complexes. This might be due to the presence of PL 188, which helps in solubility enhancement of GS. DSC, XRD and SEM evaluation confirmed the modification in the structure of GS. FTIR and NMR results indicated the formation of an inclusion complex. The antioxidant and antimicrobial activity results revealed that GS TC has shown significant (p < 0.05) higher activity than pure GS. The cytotoxicity study results also depicted concentration-dependent cytotoxicity. GS TC exhibited significantly (p < 0.05) high cytotoxicity to cancer cells (IC50 = 225 µg/mL) than pure GS (IC50 = 480 µg/mL). Finally, it was concluded that a remarkable enhancement in the dissolution was observed after the inclusion of GS in the ternary complex and it therefore has significant potential for the treatment of breast cancer.

Highlights

IntroductionWorldwide, Worldwide,breast breastcancer cancerisisone oneofofthe themost mostcommon commoncancers cancersamong amongwomen womenand andthe the leading cause of death after lung cancer.The prognosis of this cancer is about five years in leading cause of death after lung cancer
Genistein (GS), Poloxamer 188 (PL 188), methanol, ethanol and acetonitrile were procured from Sigma Aldrich
Our study showed greater solubility than prepared binary system and reported formulated binary inclusion complex using GS with γCD at and reported with γCD complex

Summary

Introduction

Worldwide,breast breastcancer cancerisisone oneofofthe themost mostcommon commoncancers cancersamong amongwomen womenand andthe the leading cause of death after lung cancer. The prognosis of this cancer is about five years in leading cause of death after lung cancer. The prognosis of this cancer is about five years of women [1]. Chemotherapy and and radiation therapies are commonly used used treatment in 75%. Chemotherapy radiation therapies are commonly treatmodules for thisfor type oftype cancer. The application of traditional chemotherapy ment modules this of cancer

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