In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres

• Published in: Journal of microencapsulation 2004-06, Vol.21 (4), p.371-384
• Main Authors: Ribeiro-Costa, R. M., Alves, A. J., Santos, N. P., Nascimento, S. C., Gonçalves, E. C. P., Silva, N. H., Honda, N. K., Santos-Magalhães, N. S.
• Format: Article
• Language: English
• Subjects: Animals; anti-tumour activity; Antineoplastic Agents - analysis; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Benzofurans - analysis; Benzofurans - pharmacology; Benzofurans - therapeutic use; Biological and medical sciences; Cell Proliferation - drug effects; Chromatography, High Pressure Liquid; Cladonia substellata; cytotoxicity; Drug Carriers; Drug Compounding - methods; General pharmacology; Lactic Acid; Liver - drug effects; Male; Medical sciences; Mice; Mice, Inbred Strains; Microscopy, Electron, Scanning; Microspheres; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA microspheres; Polyglycolic Acid; Polymers; Sarcoma 180 - drug therapy; Usnic acid
• ISSN: 0265-2048; 1464-5246
• DOI: 10.1080/02652040410001673919

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 µm. The usnic acid encapsulation efficiency was ∼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 µg 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.