Development of Usnic Acid Embedded Eudragit Microspheres for Alleviation of Nosocomial Infections

Author(s): Shraddha Pandey*, Shashi K. Misra, Nisha Sharma.

Journal Name: Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry

Volume 18 , Issue 1 , 2020

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Abstract:

Background: Usnic Acid has been progressively reported in the literature as one of the chiefly significant lichen metabolites exemplified by an ample diversity of applications such as antimicrobial, antifungal, antiviral, antiprotozoal agents, etc. Herein, we shed a light on nosocomial infections and formulated topical microspheres loaded with Usnic acid for improved antimicrobial activity. Recent patents and novel researches were referred to pursue the present work.

Methods: Usnic acid embedded Eudragit microspheres were designed applying solvent evaporation method, investigated for topography and drug-polymer compatibility studies. Dialysis bag method was utilized for studying drug release kinetics. In vitro antibacterial assay was carried out against the virulent bacterial strain of Staphylococcus aureus using the disc diffusion method.

Results: Topography studies revealed the formation of regular, micro-sized, smooth surface microspheres. Well defined and specific structural peaks were obtained from FTIR and TGA studies, revealing drugpolymer compatibility. The dissolution profile suggested Korsmeyer Peppas kinetic and Fickian kind of diffusion from microspheres. The pre-eminent activity of formulated microspheres was visualized from the disc diffusion study against Staphylococcus aureus.

Conclusion: The strong biological activity of Usnic acid –loaded Eudragit RS and Eudragit RL microspheres provides a promising application for corresponding material as a bactericidal agent for the alleviation of nosocomial infection. Findings paid attention to the potential of usnic acid microspheres for effective treatment of dermal and nosocomial infections caused by S. aureus.

Keywords: Antimicrobial, usnic acid, biocompatible, nosocomial infection, controlled release, microspheres.

[1]
Şahin, S.; Oran, S.; Şahintürk, P.; Demir, C.; Öztürk, Ş. Ramalina lichens and their major metabolites as possible natural antioxidant and antimicrobial agents. J. Food Biochem., 2015, 39(4), 471-477.
[http://dx.doi.org/10.1111/jfbc.12142]
[2]
Knop, W. Chemisch‐physiologischeUntersuchungüber die Flechten. Justus Liebigs Ann. Chem., 1844, 49(2), 103-124.
[http://dx.doi.org/10.1002/jlac.18440490202]
[3]
Shtro, A.A.; Zarubaev, V.V.; Luzina, O.A.; Sokolov, D.N.; Kiselev, O.I.; Salakhutdinov, N.F. Novel derivatives of usnic acid effectively inhibiting reproduction of influenza A virus. Bioorg. Med. Chem., 2014, 22(24), 6826-6836.
[http://dx.doi.org/10.1016/j.bmc.2014.10.033] [PMID: 25464881]
[4]
Sokolov, D.N.; Zarubaev, V.V.; Shtro, A.A.; Polovinka, M.P.; Luzina, O.A.; Komarova, N.I.; Salakhutdinov, N.F.; Kiselev, O.I. Anti-viral activity of (-)- and (+)-usnic acids and their derivatives against influenza virus A(H1N1)2009. Bioorg. Med. Chem. Lett., 2012, 22(23), 7060-7064.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.084] [PMID: 23099095]
[5]
Broksa, B.; Sturdíková, M.; Prónayová, N.; Liptaj, T. (-)-Usnic acid and its derivatives. Their inhibition of fungal growth and enzyme activity. Pharmazie, 1996, 51(3), 195-196.
[PMID: 8900875]
[6]
Vijayakumar, C.S.; Viswanathan, S.; Reddy, M.K.; Parvathavarthini, S.; Kundu, A.B.; Sukumar, E. Anti-inflammatory activity of (+)-usnic acid. Fitoterapia, 2000, 71(5), 564-566.
[http://dx.doi.org/10.1016/S0367-326X(00)00209-4] [PMID: 11449509]
[7]
Huang, Z.; Zheng, G.; Tao, J.; Ruan, J. Anti-inflammatory effects and mechanisms of usnic acid. J. Wuhan Uni. Technol.-. Mater. Sci. Ed., 2011, 26(5), 955-959.
[8]
Koparal, A.T. Anti-angiogenic and antiproliferative properties of the lichen substances (-)-usnic acid and vulpinic acid. Z. Natforsch. C J. Biosci., 2015, 70(5-6), 159-164.
[http://dx.doi.org/10.1515/znc-2014-4178] [PMID: 26136299]
[9]
O’Neill, M.A.; Mayer, M.; Murray, K.E.; Rolim-Santos, H.M.L.; Santos-Magalhães, N.S.; Thompson, A.M.; Appleyard, V.C.L. Does usnic acid affect microtubules in human cancer cells? Braz. J. Biol., 2010, 70(3), 659-664.
[http://dx.doi.org/10.1590/S1519-69842010005000013] [PMID: 20379653]
[10]
Okuyama, E.; Umeyama, K.; Yamazaki, M.; Kinoshita, Y.; Yamamoto, Y. Usnic acid and diffractaic acid as analgesic and antipyretic components of Usnea diffracta. Planta Med., 1995, 61(2), 113-115.
[http://dx.doi.org/10.1055/s-2006-958027] [PMID: 7753915]
[11]
Ramos, D.F.; Almeida da Silva, P.E. Antimycobacterial activity of usnic acid against resistant and susceptible strains of Mycobacterium tuberculosis and non-tuberculous mycobacteria. Pharm. Biol., 2010, 48(3), 260-263.
[http://dx.doi.org/10.3109/13880200903085490] [PMID: 20645810]
[12]
Okigbo, R.N.; Ogbonnaya, U.O. Antifungal effects of two tropical plant leaf extracts (Ocimumgratissimum and Aframomummelegueta) on postharvest yam (Dioscorea spp.) rot. Afr. J. Biotechnol., 2006, 5(9), 727-731.
[13]
Silver, L.L.; Bostian, K.A. Discovery and development of new antibiotics: the problem of antibiotic resistance. Antimicrob. Agents Chemother., 1993, 37(3), 377-383.
[http://dx.doi.org/10.1128/AAC.37.3.377] [PMID: 8460908]
[14]
Weiner, L.M.; Webb, A.K.; Limbago, B.; Dudeck, M.A.; Patel, J.; Kallen, A.J.; Edwards, J.R.; Sievert, D.M. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the centers for disease control and prevention, 2011–2014. Infect. Control Hosp. Epidemiol., 2016, 37(11), 1288-1301.
[http://dx.doi.org/10.1017/ice.2016.174] [PMID: 27573805]
[15]
Bagheri Nejad, S.; Allegranzi, B.; Syed, S.B.; Ellis, B.; Pittet, D. Health-care-associated infection in Africa: a systematic review. Bull. World Health Organ., 2011, 89(10), 757-765.
[http://dx.doi.org/10.2471/BLT.11.088179] [PMID: 22084514]
[16]
Cocchietto, M.; Skert, N.; Nimis, P.L.; Sava, G. A review on usnic acid, an interesting natural compound. Naturwissenschaften, 2002, 89(4), 137-146.
[http://dx.doi.org/10.1007/s00114-002-0305-3] [PMID: 12061397]
[17]
Kinoshita, Y.; Yamamoto, Y.; Yoshimura, I. Distribution of optical isomers of usnic and isousnic acids analyzed by high-performance liquid chromatography. J. Hattori Bot. Lab., 1997, (83), 173-178.
[18]
Sokolov, A.; Aranson, I.S. Physical properties of collective motion in suspensions of bacteria. Phys. Rev. Lett., 2012, 109(24)248109
[http://dx.doi.org/10.1103/PhysRevLett.109.248109] [PMID: 23368392]
[19]
Mayer, M.; O’Neill, M.A.; Murray, K.E. Santos- Magalhaes, N.S. Usnic acid:a non genotoxic compound with anti- cancer properties. Anticancer Drugs, 2005, 16(8), 805-809.
[20]
da Silva Barros, M.E.; de Assis Santos, D.; Hamdan, J.S. Evaluation of susceptibility of Trichophyton mentagrophytes and Trichophyton rubrum clinical isolates to antifungal drugs using a modified CLSI microdilution method (M38-A). J. Med. Microbiol., 2007, 56(Pt 4), 514-518.
[http://dx.doi.org/10.1099/jmm.0.46542-0] [PMID: 17374893]
[21]
Burlando, B.; Ranzato, E.; Volante, A.; Appendino, G.; Pollastro, F.; Verotta, L. Antiproliferative effects on tumour cells and promotion of keratinocyte wound healing by different lichen compounds. Planta Med., 2009, 75, 607-613.
[http://dx.doi.org/10.1055/s-0029-1185329] [PMID: 19199230]
[22]
Verma, N.; Behera, B.C.; Joshi, A. Studies on nutritional requirement for the culture of lichen Ramalina nervulosa and Ramalina pacifica to enhance the production of antioxidant metabolites. Folia Microbiol. (Praha), 2012, 57(2), 107-114.
[http://dx.doi.org/10.1007/s12223-012-0100-2] [PMID: 22351563]
[23]
Suwalsky, M.; Jemiola-Rzeminska, M.; Astudillo, C.; Gallardo, M.J.; Staforelli, J.P.; Villena, F.; Strzalka, K. An in vitro study on the antioxidant capacity of usnic acid on human erythrocytes and molecular models of its membrane. Biochim. Biophys. Acta, 2015, 1848(11 Pt A), 2829-2838.
[http://dx.doi.org/10.1016/j.bbamem.2015.08.017] [PMID: 26299817]
[24]
Halama, P.; Van Haluwin, C. Antifungal activity of lichen extracts and lichenic acids. BioControl, 2004, 49(1), 95-107.
[http://dx.doi.org/10.1023/B:BICO.0000009378.31023.ba]
[25]
Douglas, A.E. Symbiosis as a general principle in eukaryotic evolution. Cold Spring Harb. Perspect. Biol., 2014, 6(2)a016113
[http://dx.doi.org/10.1101/cshperspect.a016113] [PMID: 24492707]
[26]
Dehghan, S.; Aboofazeli, R.; Avadi, M.; Khaksar, R. Formulation optimization of nifedipine containing microspheres using factorial design. Afr. J. Pharm. Pharmacol., 2010, 4(6), 346-354.
[27]
Midha, K.; Nagpal, M.; Arora, S. Microspheres: a recent update. Int. J. Recent Sci. Res., 2015, 6, 5859-5867.
[28]
Surini, S.; Anggriani, V.; Anwar, E. Study of mucoadhesive microspheres based on pregelatinized. J. Med. Sci, 2009, 9(6), 249-256.
[http://dx.doi.org/10.3923/jms.2009.249.256]
[29]
Chowdary, K.P.R.; Babu, J.S. The permeability of ethylene vinyl acetate copolymer microcapsules: Effect of solvents. Indian J. Pharm. Sci., 2003, 65(1), 62.
[30]
Araújo, E.S.; Pereira, E.C.; da Costa, M.M.; da Silva, N.H.; de Oliveira, H.P. bactericidal activity of usnic acid-loaded electrospun fibers. Recent Pat. Nanotechnol., 2016, 10(3), 252-257.
[http://dx.doi.org/10.2174/1872210510666160517160144] [PMID: 27184396]


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Article Details

VOLUME: 18
ISSUE: 1
Year: 2020
Page: [79 - 87]
Pages: 9
DOI: 10.2174/2211352517666190126161205

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