Copaifera langsdorffii: development of liposomes stabilized by spray freeze drying with selective antitumor action

• Grant number: 12/02082-1
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2012
• End date: November 30, 2015
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Luis Alexandre Pedro de Freitas
• Grantee: Ana Rita de Mello Costa
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 11/13630-7 - Chemical and pharmacological validation of extracts and active compounds of Copaifera species, AP.TEM
• Associated scholarship(s): 13/16268-2 - Study on the selective extraction of copaiba compounds using supercritical fluid technology, BE.EP.DR

Abstract

In spite of the marketing and international incentive and the wide Brazilian biodiversity and medicinal plant consume, Brazil is still weak in development and technological research of native medicinal plant as Copaifera langsdorffii. The oil of this specie is broadly used by Brazilians as antiinflamatory, analsegic and muscle relaxant and it contains diterpenes of kauran, clerodan and labdan series. There are studies that report Copaifera sp. genus antitumor activity using so the oil as the extract, frations and isolated compounds as the kaurenoic acid. This compound presents potencial cytotoxic, however, also presents low selectivity to the tumoral cells. Since the antitumor action is neither specific nor acts directly in the tumor, it can cause adverse effects. So the development of delivery systems as liposomes makes possible to protect the active and to increase the drug selectivity to the tumor. The knowledge on liposomes formulation made possible its specific deposition on the tumor decreasing the free drug circulating concentration and restricting the drug distribution to non cancinogenic tissue. A way to make selective liposomes is to use folic acid as anchor, because it is recognized by folate receptors highly expressed on tumoral cells. To insert polyethileneglycol (PEG) conjugated to the lipides also can increase the deposition of the drug in the tumor and change the biodistribution of the liposomes in the blood. However, the liposomes still present some challenges as the short blood circulating time before the macrophages attack, the physical and chemical instability of aqueous dispersion, low encapsulation or drug leakage and aggregation. Some of these disadvantages can be solved by techniques that improve the physico-chemical stability as the liposome drying by spray freeze drying. It consists in spraying the sample on liquid nitrogen, also called cryogen, which provides low temperature. The cryogen is enough to freeze the sprayed sample and, then, the sample is dehydrated by sublimation. In this context, this project proposes to develop liposome formulations containg C. langsdorffii extract/ oil using the kaurenoic acid as the chemical marker, which presents tumoral cells inhibition, and to increase its physico-chemical stability by spray freeze drying as well as its selective antitumoral action. Therefore, this project is justified to its importance to aggregate value to two national technological areas: the technological development of phytomedicines and the utilization of a new drying process.

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, Ana Rita de Mello. Loaded liposomes with kaurenoic acid or Copaifera langsdorffii extract: development, characterization, antitumor and tripanocide activities. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.