Formulation and Evaluation of Usnic Acid Isolated From Lichens of South India as Specific Targeting Agents for Cytotoxic Activity

Abstract

In the present study usnic acid was isolated from lichens of South India and eight derivatives of usnic acid were synthesized and characterized by IR, 1HNMR and 13CNMR spectral data. Cytotoxic and toxicicological evaluation of usnic acid and its derivatives were carried out. The result of cytotoxic evaluation indicated that usnic acid and its derivatives showed significant cytotoxic activity and among these compounds COMPD VIII and COMPD USA showed maximum cytotoxic activity. However COMPD VIII has higher LD50 value and produced more hepatotoxicity than COMPD USA. Hence COMPD USA (usnric acid) was selected and formulated into nanoparticles to achieve controlled as well as targeted drug delivery with increased cytotoxic activity and reduced hepatotoxicity. Various batches of usnicacid loaded nanoparticles were prepared by Nanoprecipitation method with and without sonication technique using biodegradable polymers PLA and PLGA. Sonicated nanoparticles were of smaller in size with effectively controlled drug content than unsonicated nanoparticles. The SEM photograph of usnicacid nanoparticles showed that particles were spherical shape with smooth surface. DSC analysis revealed that both drug and polymer were in amorphous state in formulation and there was no interaction between drug and polymer. The stability results revealed that there was not much reduction in drug content as well as drug release when the optimized formulation was stored at 4° 2°C and 25+2°C/60%+5% RH. Hence the formulation was stable at 4 °C and 25 °C. From the above discussion it was concluded that usnic acid loaded nanoparticles formulated using biodegradable polymers PLA and PLGA achieved controlled release of drug at targeted site and produced enhanced cytotoxic activity with considerably reduced hepatotoxicity. As an extention of the work the formulation could be used for higher animal studies and clinical studies to check the efficacy of the selected formulation. newline