Cationic Okra gum coated nanoliposomes as a pH-sensitive carrier for co-delivery of hesperetin and oxaliplatin in colorectal cancers

Abstract

Oxaliplatin (OXP) is the typical treatment for colorectal cancer. Combining chemotherapeutic drugs can reduce drug resistance and side effects. In the present study, the co-delivery of OXP with Hesperetin (HSP), a natural anti-cancer flavonoid, by nanoliposomes was studied against HT-29 colon cancer cells. Cationic Okra gum (COG) was synthesized to coat nanoliposomes. The successful synthesis of COG was confirmed by NMR spectroscopy. Liposomes were prepared by thin film hydration technique. Formulations containing 0.5, 1, and 2 mg·ml⁻¹ COG, had particle sizes ranging from 145 to 175 nm and zeta potentials for uncoated and coated formulations changed between −29 and −0.403 mV. Coated liposomes released 98 and 66% of HSP and OXP, respectively during 24 h pH-dependently. Cationic Okra gum enhanced the physical stability of the liposomes for about 30 days. The composite liposomes containing OXP and HSP at final concentrations of 1.125 and 125 µM, respectively could generate significant cytotoxicity at 48 h in comparison to each drug alone. Extracted drug-target interactions from the STITCH database, showed that Catalase (CAT) is the common target between OXP and HSP drugs. Measurement of the CAT activity may be used as an indicator to investigate the mechanism of action of these drugs in subsequent experiments.

Graphical Abstract

Keywords:

• Oxaliplatin
• hesperetin
• nanoliposomes
• cationic Okra gum
• colorectal cancer
• pH sensitive

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors appreciate the financial support of Iran’s National Elites Foundation by grant No # 15/13610 and Isfahan University of Medical Sciences.