Neomenthol, a cyclic monoterpenoid, is a stereoisomer of menthol present in the essential oil of Mentha spp. It is used in food as a flavoring agent, in cosmetics and medicines because of its cooling effects. However, neomenthol has not been much explored for its anticancer potential. Additionally, targeting hyaluronidase, Cathepsin-D, and ODC by phytochemicals is amongst the efficient approach for cancer prevention and/or treatment.
To investigate the molecular and cell target-based antiproliferative potential of neomenthol on human cancer (A431, PC-3, K562, A549, FaDu, MDA-MB-231, COLO-205, MCF-7, and WRL-68) and normal (HEK-293) cell lines.
The potency of neomenthol was evaluated on human cancer and normal cell line using SRB, NRU and MTT assays. The molecular target based study of neomenthol was carried out in cell-free and cell-based test systems. Further, the potency of neomenthol was confirmed by quantitative real-time PCR analysis and molecular docking studies. The in vivo anticancer potential of neomenthol was performed on mice EAC model and the toxicity examination was accomplished through in silico, ex vivo and in vivo approaches.
Neomenthol exhibits a promising activity (IC50 17.3 ± 6.49 μM) against human epidermoid carcinoma (A431) cells by arresting the G2/M phase and increasing the number of sub-diploid cells. It significantly inhibits hyaluronidase activity (IC50 12.81 ± 0.01 μM) and affects the tubulin polymerization. The expression analysis and molecular docking studies support the in vitro molecular and cell target based results. Neomenthol prevents EAC tumor formation by 58.84% and inhibits hyaluronidase activity up to 10% at 75 mg/kg bw, i.p. dose. The oral dose of 1000 mg/kg bw was found safe in acute oral toxicity studies.
Neomenthol delayed the growth of skin carcinoma cells by inhibiting the tubulin polymerization and hyaluronidase activity, which are responsible for tumor growth, metastasis, and angiogenesis.

The most preferable mode of drugs administration is via the oral route but physiological barriers such as pH, enzymatic degradation etc. limit the absolute use of this route. Herein lies the importance of nanotechnology having a wide range of applications in the field of nano-medicine, particularly in drug delivery systems. The exclusive properties particularly small size and high surface area (which can be modified as required), exhibited by these nanoparticlesrender these structures more suitable for the purpose of drug delivery. Various nanostructures, like liposomes, dendrimers, mesoporous silica nanoparticles, etc. have been designed for the said purpose. These nanostructures have several advantages over traditional administration of medicine. Apart from overcoming the pharmacokinetic and pharmacodynamics limitations of many potential therapeutic molecules, they may also be useful for advanced drug delivery purposes like targeted drug delivery, controlled release, enhanced permeability and retention (EPR) effect. In this review, we attempt to describe an up-to-date knowledge on various strategically devised nanostructures to overcome the problems related to oral drug administration.