benzofurans and Sarcoma-180

Despite the recognised antiproliferative and antitumour properties of usnic acid, its therapeutic application has yet to be introduced. In fact, the high hepatotoxicity and low water solubility of usnic acid have somewhat restricted its practical use in anticancer therapy. The aim of this study was therefore to investigate the antitumour activity of usnic acid encapsulated into nanocapsules prepared with lactic co-glycolic acid polymer. Usnic acid-loaded nanocapsules were obtained using the interfacial deposition of a preformed polymer. The antitumour activity was confirmed on an ascitic tumour (Sarcoma-180) implanted in Swiss mice and estimated by means of the tumour inhibition. The results of antitumour activity confirmed that the encapsulation of usnic acid into PLGA-nanocapsules produced a 26.4% increase in tumour inhibition as compared with the standard free usnic acid treatment. Vacuolization of hepatocytes and a mild lymphocytic infiltration in portal spaces were observed in animals treated with free usnic acid. However, this hepatotoxicity was substantially reduced when animals were treated with usnic acid-loaded nanocapsules. No histological changes were noticed in the kidneys or spleen of animals treated either with usnic acid or usnic acid-loaded nanocapsules. These results suggest that nanoencapsulation may be a way of enabling usnic acid to be used in chemotherapy.

Topics: Animals; Benzofurans; Cell Line, Tumor; Chemical and Drug Induced Liver Injury; Disease Progression; Drug Compounding; Injections, Intraperitoneal; Lactic Acid; Liver; Male; Mice; Nanostructures; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Sarcoma 180; Survival Analysis

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15 mg kg(-1) weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02 +/- 2.72 microm. The usnic acid encapsulation efficiency was approximately 100% (UA 10 mg 460 mg(-1) microspheres). A maximum release of 92% was achieved at the fifth day. The IC50 values for free and encapsulated usnic acid were 12 and 14 microg ml(-1), respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.

Topics: Animals; Antineoplastic Agents; Benzofurans; Cell Proliferation; Chromatography, High Pressure Liquid; Drug Carriers; Drug Compounding; Lactic Acid; Liver; Male; Mice; Mice, Inbred Strains; Microscopy, Electron, Scanning; Microspheres; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Sarcoma 180