title: Toxicity evaluation of cordycepin and its delivery system for sustained in vitro anti-lung cancer activity.
abstract: In the previous study, we have found that the cordycepin which was extracted from Cordyceps mycelia produced by growing Cordyceps militaris on the dead larva of Bombyx mori silkworms showed the anti-proliferative effect toward lung cancer cells without toxicity to non-cancer cells. In this work, the cordycepin was tested for its in vitro mutagenicity and in vivo toxicity. From the Ames test and subacute toxicity test using oral administration in a rat model, the cordycepin was proved to be a non-mutagenic and non-toxic compound. The hematology and blood chemistry as well as the microanatomical characteristic of the tissues of rats fed with cordycepin every day for consecutive 30 days were comparable to those of the normal ones. Then, the cordycepin was incorporated in gelatin type A (GA) and gelatin type B (GB) nanoparticles aimed to sustain its release and activity. The cordycepin incorporated in both GA and GB nanoparticles showed the sustained release profiles. GA nanoparticles could encapsulate cordycepin at higher encapsulation efficiency due to the attractive electrostatic interaction between the positive-charged GA and the negative-charged cordycepin. However, GA nanoparticles released cordycepin at the higher amount possibly because of the large surface area of small size nanoparticles. Comparing to GB nanoparticles, the higher amount of cordycepin released from GA nanoparticles showed the higher anti-proliferative and anti-migratory effects on A549 lung cancer cells. In conclusion, GA nanoparticles were suggested as a suitable carrier for the sustained release of cordycepin. The GA nanoparticles releasing cordycepin could be an effective and non-invasive material for the treatment of lung cancer cells.
authors.affiliation: Bioactive Resources for Innovative Clinical Applications Research Unit and Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, PhayaThai Road, Phatumwan, Bangkok 10330 Thailand.
authors.forename: Pornanong
authors.initials: P
authors.lastname: Aramwit
authors.affiliation: Division of Pharmacognosy and Toxicology, Faculty of Pharmaceutical Sciences, KhonKaen University, Mittraphap Road, TambonMuang, KhonKaen 40002 Thailand.
authors.forename: Supatra
authors.initials: S
authors.lastname: Porasuphatana
authors.affiliation: Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, 15 Karnjanavanich Rd, Hat Yai, Songkla 90110 Thailand.
authors.forename: Teerapol
authors.initials: T
authors.lastname: Srichana
authors.affiliation: Department of Pharmaceutical Technology and Drug Delivery System Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, 15 Karnjanavanich Rd, Hat Yai, Songkla 90110 Thailand.
authors.forename: Titpawan
authors.initials: T
authors.lastname: Nakpheng
keywords: Cordycepin; Gelatin; Lung cancer; Nanoparticles; Sustained release; Toxicity