Study of the action of curcumin-nanoparticles in HPV-16 positive cervical carcinoma cells

Abstract

Human Papillomavirus (HPV) are a DNA virus family with more than 180 types, and are divided in high and low risk HPVs. The most important high risk HPVs are the HPV-16 and -18, that together are responsible for more than 70% cervical carcinoma cases. The HPV has tropism by for cutaneous or mucosal epithelial surfaces. Treatment options include surgery, cryogenics, drugs and antiviral therapies. However, the use of drugs has side effects such as pain, redness, itching, burning and hypersensitivity. The use of a natural compound with anticarcinogenic and antiviral properties in association with a nanoparticle increases the cellular uptake and bioavailability and decreases the intracellular metabolism speed. Curcumin is a very versatile bioactive hydrophobic compound which has anti-inflammatory, anti-hyperlipidaemic, anti-angiogenic, anti-neoplastic and chemoprotective properties, and also has the hability to decrease the expression of HPV oncogenes. However, curcumin application as an active agent has been limited by low water solubility and bioavailability. The drug delivery system by nanoemulsions allows that lipophilic compounds behave as amphiphilic compounds in biological systems, increasing the compatibility, bioavailability and drug efficacy. The nanospheres are another kind of drug delivery system that offers many pharmaceutical advantages in the delivery of hydrophobic drugs, such as the increase of stability with improvement of pharmacokinetics and hemocompatibility. The increasing need for noninvasive antiviral treatment, with few or no side effects, is due to the large number of people infected by HPV, thereby, the nanotechnology associated with natural compounds may be a future treatment. The aims of this project are to analyze the action of curcumin associated nanoemulsions and nanospheres on the expression of HPV-16 oncogenes E5, E6 and E7 and on the target genes of HPV oncogenes in HPV-16 positive cervical carcinoma cells lineage (in vitro), and to analyze the action of the nanoparticle that showed the best results on the inhibition of high risk HPV oncogenes and in target genes in inoculated mouse with in lineage of cervical carcinoma (in vivo).