Generic placeholder image

Anti-Infective Agents

Author(s): Rakeshkumar Parmar*, Nimisha Kalal, Janki Patel and Payal Chauhan

DOI: 10.2174/2211352521666230905140633

DownloadDownload PDF Flyer Cite As
Fabrication of Eucalyptus Oil-loaded Ciprofloxacin Hydrochloride Topical Films for Enhanced Treatment of Post-Operative Wound Infection

Article ID: e050923220729 Pages: 11

  • * (Excluding Mailing and Handling)

Abstract

Background: The efficacious penetration of antimicrobials at infectious sites and the reduction of microbial resistance development are critical in controlling the effective treatment of post-operative wound infection.

Methods: To create the enhanced antimicrobial topical films, a solvent casting method for ciprofloxacin hydrochloride (CiproHCl) loaded eucalyptus oil (EO) containing low molecular weight chitosan films was used. Nine batches of CiproHCl with varying chitosan and glycerol concentrations were prepared and tested. Additionally, optimised CiproHCl films with EO were created and tested. The antimicrobial activity of CiproHCl-loaded EO containing low molecular weight chitosan films against S. aureus, E. coli, and B. subtilus was tested.

Results: The FT-IR spectroscopy and DSC analysis revealed no interaction between the drug and any of the other excipients, and the drug remained amorphous in chitosan film. The SEM analysis revealed that the prepared CiproHCl-loaded EO-containing films had smooth surfaces and large agglomerates. In vitro drug release testing revealed that the EO-loaded films have a sustained release profile of up to 16 hours with a cumulative drug release of 96.83%. In an ex vivo drug permeation study, CiproHCl-loaded EO-containing films demonstrated 2.44 times more permeation flux than CiproHCl-alone films. After six months, the stability study revealed that the CiproHCl-loaded EO-loaded EO-containing film showed no significant change in drug release profile or folding endurance.

Conclusion: This present study highlights the possible usage of CiproHCl-loaded EO containing low molecular weight chitosan films in enhanced post-operative wound treatment.

Graphical Abstract

[1]
Liang, Y.; Liang, Y.; Zhang, H.; Guo, B. Antibacterial biomaterials for skin wound dressing. Asian J. Pharm. Sci., 2022, 17(3), 353-384.
[http://dx.doi.org/10.1016/j.ajps.2022.01.001] [PMID: 35782328]
[2]
Üstündağ Okur, N.; Hökenek, N.; Okur, M.E.; Ayla, Ş.; Yoltaş, A.; Siafaka, P.I.; Cevher, E. An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery. Saudi Pharm. J., 2019, 27(5), 738-752.
[http://dx.doi.org/10.1016/j.jsps.2019.04.010] [PMID: 31297030]
[3]
Smith, J.K.; Bumgardner, J.D.; Courtney, H.S.; Smeltzer, M.S.; Haggard, W.O. Antibiotic-loaded chitosan film for infection prevention: A preliminary in vitro characterization. J. Biomed. Mater. Res. B Appl. Biomater., 2010, 94(1)
[http://dx.doi.org/10.1002/jbm.b.31642] [PMID: 20524196]
[4]
Vivcharenko, V.; Przekora, A. Modifications of wound dressing with bioactive agents to achieve improved pro-healing properties. Appl. Sci., 2021, 11(9), 4114.
[http://dx.doi.org/10.3390/app11094114]
[5]
De Luca, I.; Pedram, P.; Moeini, A.; Cerruti, P.; Peluso, G.; Di Salle, A.; Germann, N. Nanotechnology development for formulating essential oils in wound dressing materials to promote the wound-healing process: A review. Appl. Sci., 2021, 11(4), 1713.
[http://dx.doi.org/10.3390/app11041713]
[6]
Labib, R.M.; Ayoub, I.M.; Michel, H.E.; Mehanny, M.; Kamil, V.; Hany, M.; Magdy, M.; Moataz, A.; Maged, B.; Mohamed, A. Appraisal on the wound healing potential of Melaleuca alternifolia and Rosmarinus officinalis L. essential oil-loaded chitosan topical preparations. PLoS One, 2019, 14(9), e0219561.
[http://dx.doi.org/10.1371/journal.pone.0219561] [PMID: 31525200]
[7]
Rosa, J.M.; Bonato, L.B.; Mancuso, C.B.; Martinelli, L.; Okura, M.H.; Malpass, G.R.P.; Granato, A.C. Antimicrobial wound dressing films containing essential oils and oleoresins of pepper encapsulated in sodium alginate films. Cienc. Rural, 2018, 48(3), e20170740.
[http://dx.doi.org/10.1590/0103-8478cr20170740]
[8]
Yücedag, F.; Atalay-Oral, C.; Erkal, S.; Sirkecioglu, A.; Karasartova, D.; Sahin, F.; Tantekin-Ersolmaz, S.B.; Güner, F.S. Antibacterial oil-based polyurethane films for wound dressing applications. J. Appl. Polym. Sci., 2010, 115(3), 1347-1357.
[http://dx.doi.org/10.1002/app.30788]
[9]
Simões, D.; Miguel, S.P.; Ribeiro, M.P.; Coutinho, P.; Mendonça, A.G.; Correia, I.J. Recent advances on antimicrobial wound dressing: A review. Eur. J. Pharm. Biopharm., 2018, 127, 130-141.
[http://dx.doi.org/10.1016/j.ejpb.2018.02.022] [PMID: 29462687]
[10]
Miguel, S.P.; Moreira, A.F.; Correia, I.J. Chitosan based-asymmetric membranes for wound healing: A review. Int. J. Biol. Macromol., 2019, 127, 460-475.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.01.072] [PMID: 30660567]
[11]
Bachir, R.G.; Benali, M. Antibacterial activity of the essential oils from the leaves of eucalyptus globulus against escherichia coli and staphylococcus aureus. Asian Pac. J. Trop. Biomed., 2012, 2(9), 739-742.
[http://dx.doi.org/10.1016/S2221-1691(12)60220-2] [PMID: 23570005]
[12]
Ghalem, B.R.; Mohamed, B. Antibacterial activity of leaf essential oils of eucalyptus globulus and eucalyptus camaldulensis. Afr. J. Pharm. Pharmacol., 2008, 2, 211-215.
[13]
Alhasso, B.; Ghori, M.U.; Conway, B.R. Systematic review on the effectiveness of essential and carrier oils as skin penetration enhancers in pharmaceutical formulations. Sci. Pharm., 2022, 90(1), 14.
[http://dx.doi.org/10.3390/scipharm90010014]
[14]
Caliskan, U.K.; Karakus, M.M. Essential oils as skin permeation boosters and their predicted effect mechanisms. J. Dermatol. & Skin Sci., 2020, 2, 24-30.
[15]
Herman, A.; Herman, A.P. Essential oils and their constituents as skin penetration enhancer for transdermal drug delivery: A review. J. Pharm. Pharmacol., 2015, 67(4), 473-485.
[http://dx.doi.org/10.1111/jphp.12334] [PMID: 25557808]
[16]
Fox, L.T.; Gerber, M.; Plessis, J.D.; Hamman, J.H. Transdermal drug delivery enhancement by compounds of natural origin. Molecules, 2011, 16(12), 10507-10540.
[http://dx.doi.org/10.3390/molecules161210507]
[17]
Chen, J.; Jiang, Q.D.; Wu, Y.M.; Liu, P.; Yao, J.H.; Lu, Q.; Zhang, H.; Duan, J.A. Potential of essential oils as penetration enhancers for transdermal administration of ibuprofen to treat dysmenorrhoea. Molecules, 2015, 20(10), 18219-18236.
[http://dx.doi.org/10.3390/molecules201018219] [PMID: 26457698]
[18]
Appelbaum, P.C.; Hunter, P.A. The fluoroquinolone antibacterials: Past, present and future perspectives. Int. J. Antimicrob. Agents, 2000, 16(1), 5-15.
[http://dx.doi.org/10.1016/S0924-8579(00)00192-8] [PMID: 11185413]
[19]
Davis, R.; Markham, A.; Balfour, J.A. Ciprofloxacin. Drugs, 1996, 51(6), 1019-1074.
[http://dx.doi.org/10.2165/00003495-199651060-00010] [PMID: 8736621]
[20]
Drlica, K.; Zhao, X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev., 1997, 61(3), 377-392.
[PMID: 9293187]
[21]
Hooper, D.C. Mechanisms of action of antimicrobials: Focus on fluoroquinolones. Clin. Infect. Dis., 2001, 32(Suppl. 1), S9-S15.
[http://dx.doi.org/10.1086/319370] [PMID: 11249823]
[22]
Schluter, G. Ciprofloxacin: Toxicologic evaluation of additional safety data. Am. J. Med., 1989, 87(5), S37-S39.
[http://dx.doi.org/10.1016/0002-9343(89)90018-1] [PMID: 2589381]
[23]
Anand, U.; Kurup, L.; Mukherjee, S. Deciphering the role of pH in the binding of ciprofloxacin hydrochloride to bovine serum albumin. Phys. Chem. Chem. Phys., 2012, 14(12), 4250-4258.
[http://dx.doi.org/10.1039/c2cp00001f] [PMID: 22354288]
[24]
Kamberi, M.; Tsutsumi, K.; Kotegawa, T.; Kawano, K.; Nakamura, K.; Niki, Y.; Nakano, S. Influences of urinary pH on ciprofloxacin pharmacokinetics in humans and antimicrobial activity in vitro versus those of sparfloxacin. Antimicrob. Agents Chemother., 1999, 43(3), 525-529.
[http://dx.doi.org/10.1128/AAC.43.3.525] [PMID: 10049262]
[25]
Parojčić, J.; Stojković, A.; Tajber, L.; Grbić, S.; Paluch, K.J.; Djurić, Z.; Corrigan, O.I. Biopharmaceutical characterization of ciprofloxacin HCl-ferrous sulfate interaction. J. Pharm. Sci., 2011, 100(12), 5174-5184.
[http://dx.doi.org/10.1002/jps.22707] [PMID: 21789771]
[26]
Johnson, C.E.; Wong, D.V.; Hoppe, H.L.; Bhatt-Mehta, V. Stability of ciprofloxacin in an extemporaneous oral liquid dosage form. Int. J. Pharm. Compd., 1998, 2(4), 314-317.
[PMID: 23989641]
[27]
Baker, D.S.; Waldrop, B.; Arnold, J. Compatibility and stability of cefotaxime, vancomycin, and ciprofloxacin in antibiotic lock solutions containing heparin. Int. J. Pharm. Compd., 2010, 14(4), 346-349.
[PMID: 23965543]
[28]
Ajmal, G.; Bonde, G.V.; Thokala, S.; Mittal, P.; Khan, G.; Singh, J.; Pandey, V.K.; Mishra, B. Ciprofloxacin HCl and quercetin functionalized electrospun nanofiber membrane: Fabrication and its evaluation in full thickness wound healing. Artif. Cells Nanomed. Biotechnol., 2019, 47(1), 228-240.
[http://dx.doi.org/10.1080/21691401.2018.1548475] [PMID: 30688107]
[29]
Rancan, F.; Contardi, M.; Jurisch, J.; Blume-Peytavi, U.; Vogt, A.; Bayer, I.S.; Schaudinn, C. Evaluation of drug delivery and efficacy of ciprofloxacin-loaded povidone foils and nanofiber mats in a wound-infection model based on ex vivo human skin. Pharmaceutics, 2019, 11(10), 527.
[http://dx.doi.org/10.3390/pharmaceutics11100527] [PMID: 31614886]
[30]
Contardi, M.; Heredia-Guerrero, J.A.; Perotto, G.; Valentini, P.; Pompa, P.P.; Spanò, R.; Goldoni, L.; Bertorelli, R.; Athanassiou, A.; Bayer, I.S. Transparent ciprofloxacin-povidone antibiotic films and nanofiber mats as potential skin and wound care dressings. Eur. J. Pharm. Sci., 2017, 104, 133-144.
[http://dx.doi.org/10.1016/j.ejps.2017.03.044] [PMID: 28366652]
[31]
Sannan, T.; Kurita, K.; Ogura, K.; Iwakura, Y. Studies on chitin: 7. I.r. spectroscopic determination of degree of deacetylation. Polymer, 1978, 19(4), 458-459.
[http://dx.doi.org/10.1016/0032-3861(78)90256-2]
[32]
Khoshraftar, Z.; Safekordi, A.A.; Shamel, A.; Zaefizadeh, M. Synthesis of natural nanopesticides with the origin of Eucalyptus globulus extract for pest control. Green Chem. Lett. Rev., 2019, 12(3), 286-298.
[http://dx.doi.org/10.1080/17518253.2019.1643930]
[33]
Yu, J.H.; Du, Y.M.; Zheng, H. Blend films of chitosan/gelatin. Wuhan Univ. J. Nat. Sci., 1999, 45, 440-444.
[34]
Lima, A.M.F.; Andreani, L.; Soldi, V.; Borsali, R. Influence of plasticizer addition and crosslinking process on morphology, water absorption and mechanical properties of sodium alginate films. Quim. Nova, 2007, 30, 832-837.
[35]
Rahmat, N.; Abdullah, A.Z.; Mohamed, A.R. Recent progress on innovative and potential technologies for glycerol transformation into fuel additives: A critical review. Renew. Sustain. Energy Rev., 2010, 14(3), 987-1000.
[http://dx.doi.org/10.1016/j.rser.2009.11.010]
[36]
Aburahma, M.H.; Mahmoud, A.A. Biodegradable ocular inserts for sustained delivery of brimonidine tartarate: preparation and in vitro/in vivo evaluation. AAPS PharmSciTech, 2011, 12(4), 1335-1347.
[http://dx.doi.org/10.1208/s12249-011-9701-3] [PMID: 21979886]
[37]
Eouani, C.; Piccerelle, P.; Prinderre, P.; Bourret, E.; Joachim, J. In-vitro comparative study of buccal mucoadhesive performance of different polymeric films. Eur. J. Pharm. Biopharm., 2001, 52(1), 45-55.
[http://dx.doi.org/10.1016/S0939-6411(01)00146-1] [PMID: 11438423]
[38]
Mura, P.; Corti, G.; Cirri, M.; Maestrelli, F.; Mennini, N.; Bragagni, M. Development of mucoadhesive films for buccal administration of flufenamic acid: Effect of cyclodextrin complexation. J. Pharm. Sci., 2010, 99(7), 3019-3029.
[http://dx.doi.org/10.1002/jps.22068] [PMID: 20127823]
[39]
Lavorgna, M.; Piscitelli, F.; Mangiacapra, P.; Buonocore, G.G. Study of the combined effect of both clay and glycerol plasticizer on the properties of chitosan films. Carbohydr. Polym., 2010, 82(2), 291-298.
[http://dx.doi.org/10.1016/j.carbpol.2010.04.054]
[40]
Jayasekara, R.; Harding, I.; Bowater, I.; Christie, G.B.Y.; Lonergan, G.T. Preparation, surface modification and characterisation of solution cast starch PVA blended films. Polym. Test., 2004, 23(1), 17-27.
[http://dx.doi.org/10.1016/S0142-9418(03)00049-7]
[41]
Martins, C.S.; Morgado, D.L.; Assis, O.B.G. Cashew gum-chitosan blended films: Spectral, mechanical and surface wetting evaluations. Macromol. Res., 2016, 24(8), 691-697.
[http://dx.doi.org/10.1007/s13233-016-4103-8]
[42]
Sánchez-González, L.; Vargas, M.; González-Martínez, C.; Chiralt, A.; Cháfer, M. Characterization of edible films based on hydroxypropylmethylcellulose and tea tree essential oil. Food Hydrocoll., 2009, 23(8), 2102-2109.
[http://dx.doi.org/10.1016/j.foodhyd.2009.05.006]
[43]
Srinatha, A.; Pandit, J.K.; Singh, S. Ionic cross-linked chitosan beads for extended release of ciprofloxacin: <i> in vitro </i> characterization. Indian J. Pharm. Sci., 2008, 70(1), 16-21.
[http://dx.doi.org/10.4103/0250-474X.40326] [PMID: 20390075]
[44]
Eid, R.K.; Essa, E.A.; El Maghraby, G.M. Essential oils in niosomes for enhanced transdermal delivery of felodipine. Pharm. Dev. Technol., 2019, 24(2), 157-165.
[http://dx.doi.org/10.1080/10837450.2018.1441302] [PMID: 29441809]
[45]
Williams, A.C.; Barry, B.W. Terpenes and the lipid-protein-partitioning theory of skin penetration enhancement. Pharm. Res., 1991, 8(1), 17-24.
[http://dx.doi.org/10.1023/A:1015813803205] [PMID: 2014203]
[46]
Vasudevan, D.T.; Rajan, R. Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole. J. Adv. Pharm. Technol. Res., 2012, 3(2), 112-116.
[http://dx.doi.org/10.4103/2231-4040.97286] [PMID: 22837959]
[47]
Chowdary, K.P.R.; Kumar, P.A. Formulation and evaluation of topical drug delivery systems of ciprofloxacin. Indian J. Pharm. Sci., 1996, 58, 47-50.
[48]
Wang, Q.; Dong, Z.; Du, Y.; Kennedy, J.F. Controlled release of ciprofloxacin hydrochloride from chitosan/polyethylene glycol blend films. Carbohydr. Polym., 2007, 69(2), 336-343.
[http://dx.doi.org/10.1016/j.carbpol.2006.10.014]
[49]
Tikhonov, V.E.; Stepnova, E.A.; Babak, V.G.; Yamskov, I.A.; Palma-Guerrero, J.; Jansson, H.B.; Lopez-Llorca, L.V.; Salinas, J.; Gerasimenko, D.V.; Avdienko, I.D.; Varlamov, V.P. Bactericidal and antifungal activities of a low molecular weight chitosan and its N-/2(3)-(dodec-2-enyl)succinoyl/-derivatives. Carbohydr. Polym., 2006, 64(1), 66-72.
[http://dx.doi.org/10.1016/j.carbpol.2005.10.021]
[50]
Guarnieri, A.; Triunfo, M.; Scieuzo, C.; Ianniciello, D.; Tafi, E.; Hahn, T.; Zibek, S.; Salvia, R.; De Bonis, A.; Falabella, P. Antimicrobial properties of chitosan from different developmental stages of the bioconverter insect Hermetia illucens. Sci. Rep., 2022, 12(1), 8084.
[http://dx.doi.org/10.1038/s41598-022-12150-3] [PMID: 35577828]
[51]
Clavijo-Romero, A.; Quintanilla-Carvajal, M.X.; Ruiz, Y. Stability and antimicrobial activity of eucalyptus essential oil emulsions. Food Sci. Technol. Int., 2019, 25(1), 24-37.
[http://dx.doi.org/10.1177/1082013218794841] [PMID: 30149730]
[52]
Insuan, W.; Chahomchuen, T. Chemical composition and antimicrobial activity of essential oil extracted from eucalyptus citriodora leaf. Han’guk Misaengmul, Saengmyong Konghakhoe Chi., 2020, 48(2), 148-157.
[http://dx.doi.org/10.4014/mbl.1912.12016]
[53]
Inoue, S.; Ishihara, H.; Uchida, K.; Yamaguchi, H. Preferential percutaneous absorption of monoterpene hydrocarbons and ester of essential oils in mice placed in aroma bath and alteration of compositions of essential oils. Aroma Res., 2000, 1, 75-83.
[54]
Jager, W.; Buchbauer, G.; Jirovetz, L. Percutaneous absorption of lavender oil from a massage oil. J. Soc. Cosmet. Chem., 1992, 43, 49-54.
[55]
Diliberto, J.J.; Usha, G.; Birnbaum, L.S. Disposition of citral in male Fischer rats. Drug Metab. Dispos., 1988, 16(5), 721-727.
[PMID: 2906597]