Amorphous nano morin outperforms native molecule in anticancer activity and oral bioavailability

Abstract

In the past decade, naturally occurring phytoconstituents have emerged as potential therapeutic agents and alternative to synthetic drugs. However, efficient delivery of hydrophobic phytoconstituents into the body with desired therapeutic efficacy is a key challenge for the pharmaceutical industries due to their insolubility in water and low oral bioavailability. Nanosuspension formulations have shown promises to improve the delivery of the hydrophobic molecules with simultaneously avoiding the drawbacks like carrier toxicity and scale-up issues of other nanotechnology-based drug delivery systems. In this study, we have used morin hydrate (MH), a flavonol, and developed MH nanosuspension formulation (MHNS) to improve its poor physiochemical properties and low oral bioavailability. Different stabilizers with varying concentrations were investigated for preparing nanosuspension. MHNS was characterized by DLS, TEM, FTIR, DSC, powder XRD and was evaluated for its solubility, dissolution, partition coefficient, in-vitro anticancer activity and pharmacokinetics in rats. The optimized nanosuspension formulation, with a size of <100 nm, is capable of increasing aqueous solubility, dissolution rate, and oral bioavailability of MH. Moreover, the therapeutic efficacy, in terms of cytotoxicity to human lung cancer cells, of MH was also increased after formulating into nanosuspension form.

Keywords:

• Morin hydrate
• surfactants
• nanosuspension
• A549 cell line
• pharmacokinetic study

Acknowledgments

The authors thank Central University of Gujarat, Gandhinagar for providing necessary facilities and support. H. K. acknowledges Department of Science and Technology, New Delhi, for an INSPIRE Faculty Award. A. K. J., N. G., and P. J. acknowledges University Grant Commission, New Delhi for Ph.D. fellowships. H. A. acknowledges Department of Science and Technology, Govt. of India for INSPIRE fellowship. The authors would like to thanks Dr Sistla Ramakrishna, Senior Principal Scientist, Applied Biology Department, CSIR – Indian Institute of Chemical Technology, Hyderabad for helping in pharmacokinetic study.

Disclosure statement

The authors declare no conflict of interest.

Supporting information

• Particle sizes of nanosuspensions prepared with different types of surfactants and polymer; Zeta potential values of nanosuspensions prepared with different types of surfactant and polymer.