Improved delivery of the anticancer agent citral using BSA nanoparticles and polymeric wafers

Abstract

Benjamin White,1 Anna Evison,1 Eszter Dombi,1 Helen E Townley1,2 1Nuffield Department of Obstetrics and Gynaecology, Women’s Centre, John Radcliffe Hospital, 2Department of Engineering Science, Oxford University, Oxford, UK Abstract: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, with a 5-year survival rate of between 30 and 65%. Standard treatment involves surgery, radiation treatment, and chemotherapy. However, there is a high recurrence rate, particularly from locoregional spread. We investigated the use of the natural compound citral (3,7-dimethyl-2,6-octadienal), which can be found in a number of plants, but is particularly abundant in lemon grass (Cymbopogon citratus) oil, for activity against immortalized RMS cells. Significant cancer cell death was seen at concentrations above 150 μM citral, and mitochondrial morphological changes were seen after incubation with 10 μM citral. However, since citral is a highly volatile molecule, we prepared albumin particles by a desolvation method to encapsulate citral, as a means of stabilization. We then further incorporated the loaded nanoparticles into a biodegradable polyanhydride wafer to generate a slow release system. The wafers were shown to degrade by 50% over the course of 25 days and to release the active compound. We therefore propose the use of the citral-nanoparticle-polymer wafers for implantation into the tumor bed after surgical removal of a sarcoma as a means to control locoregional spread due to any remaining cancerous cells. Keywords: citral, nanoparticle, wafer, biodegradable, mitochondria, toroidal, cancer, rhabdomyosarcoma, Cymbopogon citratus