J Appl Biomed 14:105-112, 2016 | DOI: 10.1016/j.jab.2015.04.006

Enhanced anti-inflammatory benefits of meloxicam-loaded lipid-core nanocapsules in a mouse pleurisy model: A comparative study with a free form drug

Francine Rodrigues Ianiskia, Fernanda D'Avila da Silvaa, Ethel Antunes Wilhelmb,*, Renata Streck Fernandesa, Marta Palma Alvesc, Marta Maria Mederios Frescura Duarted, Cristiane Lucheseb,*
a Programa de Pós Graduação em Nanociências, Centro Universitário Franciscano, CEP: 97010-032, Santa Maria, RS, Brazil
b Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, CEP: 96010-900, RS, Brazil
c Universidade Federal de Santa Maria, CEP: 97105-900, Santa Maria, RS, Brazil
d Universidade Luterana do Brasil, Departamento de Ciências da Saúde, Santa Maria, RS, Brazil

The development of new treatments for inflammation continues to be of high interest, since long-acting effect is critical for patients. We investigated whether meloxicam-loaded lipid-core nanocapsules (M-NC) have an anti-inflammatory action superior to a free drug (M-F) on a mouse pleurisy model, by analyzing the time-course of leukocytes migration in the pleural fluid. Male adult Swiss mice were divided into six groups for each time (24; 48 and 72 h) and were pretreated with blank nanocapsules (17 ml/kg) or M-NC (5 mg/kg) or free meloxicam (M-F) (5 mg/kg). After pretreatments, mice received saline (0.9%) or carrageenan (Cg) (1%) into pleural cavity. Four hours after Cg or saline administration, animals were killed, pleural cavity was washed and pleural fluid was collected for the determination of total leukocytes. Cytokines levels, differential leukocyte count and α-1-acid glycoprotein (AGP) levels were determined only at 48 h of pretreatment, which had effect on total leukocyte count. M-NC were effective against the increase in total and differential leukocyte counts and pleural exudate caused by Cg, while M-F had no effect. M-NC had superior effect to M-F against the increase in cytokines and AGP levels induced by Cg. In summary, M-NC had a superior anti-inflammatory effect to free drug in Cg-induced pleurisy, supporting the idea that the inflammatory process in tissues facilitates the vectorization of polymeric nanoparticles.

Keywords: Inflammation; Pleurisy; Nanoparticles; Cytokines; Meloxicam

Received: January 22, 2015; Revised: April 27, 2015; Accepted: April 30, 2015; Published: April 1, 2016  Show citation

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Rodrigues Ianiski F, da Silva FD, Antunes Wilhelm E, Fernandes RS, Palma Alves M, Mederios Frescura Duarte MM, Luchese C. Enhanced anti-inflammatory benefits of meloxicam-loaded lipid-core nanocapsules in a mouse pleurisy model: A comparative study with a free form drug. J Appl Biomed. 2016;14(2):105-112. doi: 10.1016/j.jab.2015.04.006.
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References

  1. Aggarwal, P., Hall, J.B., McLeland, C.B., Dobrovolskaia, M.A., McNeil, S.E., 2009. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv. Drug Deliv. Rev. 61, 428-437. Go to original source... Go to PubMed...
  2. Ah, Y., Choi, J., Choi, Y., Ki, H., Bae, J., 2010. A novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization. Int. J. Pharm. 385, 12-19. Go to original source... Go to PubMed...
  3. Alexandrakis, M.G., Coulocheri, S.A., Bouros, D., Vlachonikolis, I. G., Eliopoulos, G.D., 2000. Significance of alpha-2macroglobulin, alpha-1-acid glycoprotein, and C-reative protein in pleural effusion differentiation. J. Clin. Invest. 67, 30-35. Go to original source... Go to PubMed...
  4. Anton, N., Benoit, J.P., Saulnier, P., 2008. Design and production of nanoparticles formulated from nano-emulsion templatesa review. J. Control. Release 128, 185-199. Go to original source... Go to PubMed...
  5. Arafa, H.M.M., Abdel-Wahab, M.H., El-Shafeey, M.F., Badary, O.A., Hamada, F.M.A., 2007. Anti-fibrotic effect of meloxicam in a murine lung fibrosis model. Eur. J. Pharmacol. 564, 181-189. Go to original source... Go to PubMed...
  6. Badran, M.M., Taha, E.I., Tayel, M.M., Al-Suwayeh, S.A., 2014. Ultra-fine self nanoemulsifying drug delivery system for transdermal delivery of meloxicam: dependency on the type of surfactants. J. Mol. Liq. 190, 16-22. Go to original source...
  7. Bender, A.E., Adorne, D.M., Colomé, L.M., Abdalla, S.P.D., Guterres, S.S., Pohlmann, A.R., 2012. Hemocompatibility of poly(e-caprolactone) lipid core nanocapsules stabilized with polysorbate 80 lecithin and uncoatedorcoated with chitosan. Int. J. Pharm. 426, 271-279. Go to original source... Go to PubMed...
  8. Benvegnu, D.M., Barcelos, R.C., Boufleur, N., Reckziegel, P., Pase, C.S., Ourique, A.F., Beck, R.C., Burger, M.E., 2011. Haloperidolloaded polysorbate-coated polymeric nanocapsules increase its efficacy in the antipsychotic treatment in rats. Eur. J. Pharm. Biopharm. 77, 332-336. Go to original source... Go to PubMed...
  9. Berger, J., 2011. The age of biomedicine: current trends in traditional subjects. J. Appl. Biomed. 9, 57-61. Go to original source...
  10. Bernardi, A., Braganhol, E., Jäger, E., Figueiró, F., Edelweiss, M.I., Pohlmann, A.R., Guterres, S.S., Battastini, A.M., 2009a. Indomethacin-loaded nanocapsules treatment reduces in vivo glioblastoma growth in a rat glioma model. Cancer Lett. 18, 53-63. Go to original source... Go to PubMed...
  11. Bernardi, A., Zilberstein, A., Jager, E., Campos, M.M., Morrone, F. B., Calixto, J.B., Pohlmann, A.R., Guterres, S.S., Battastini, A. M.O., 2009b. Effects of indomethacin-loaded nanocapsules in experimental models of inflammation in rats. Br. J. Pharmacol. 158, 1104-1111. Go to original source... Go to PubMed...
  12. Bernardi, A., Frozza, R.L., Horn, A.P., Campos, M.M., Calixto, J.B., Salbego, C., Pohlmann, A.R., Guterres, S.S., Battastini, A.M., 2010. Protective effects of indomethacin-loaded nanocapsules against oxygen-glucose deprivation in organotypic hippocampal slice cultures: involvement of neuroinflammation. Neurochem. Int. 57, 629-636. Go to original source... Go to PubMed...
  13. Bogunia-Kubik, K., Sugisaka, M., 2002. From molecular biology to nanotechnology and nanomedicine. Biosystems 63, 123-138. Go to original source... Go to PubMed...
  14. Brown, P.D., Patel, P.R., 2015. Nanomedicine: a pharma perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7, 125-130. Go to original source... Go to PubMed...
  15. Couvreur, P., Barratt, G., Fattal, E., Legrand, P., Vauthier, C., 2002. Nanocapsule technology: a review. Crit. Rev. Ther. Drug Carrier Syst. 19, 99-134. Go to original source... Go to PubMed...
  16. Crisafulli, C., Mazzon, E., Paterniti, I., Galuppo, M., Bramanti, P., Cuzzocrea, S., 2010. Effects of Liver  receptor agonist treatment on signal transduction pathways in acute lung inflammation. Respir. Res. 11, 1-15. Go to original source... Go to PubMed...
  17. Dijk, W.V., Do Carmo, S., Rassart, E., Dahlbäck, B., Sodetz, J.M., 2005. The plasma lipocalins a1-acid glycoprotein, apolipoprotein D, apolipoprotein M and complement protein C8. Cell Metab. 1, 633-646.
  18. Fessi, H., Puisieux, F., Devissaguet, J.P., Amoury, N., Benita, S., 1989. Nanocapsules formation by interfacial polymer deposition following solvent displacement. Int. J. Pharm. 113, 1-4. Go to original source...
  19. Froede, T.S., Buss, Z.S., Dos Reis, G.O., Medeiros, Y.S., 2009. Evidence of anti-inflammatory effects of Pioglitazone in the murine pleurisy model induced by carrageenan. Int. Immunopharmacol. 9, 1394-1400. Go to original source... Go to PubMed...
  20. Frozza, R.L., Bernardi, A., Paese, K., Hoppe, J.B., Da Silva, T., Battastini, A.M., Pohlmann, A.R., Guterres, S.S., Salbego, C., 2010. Characterization of trans-resveratrol-loaded lipid-core nanocapsules and tissue distribution studies in rats. J. Biomed. Nanotechnol. 6, 694-703. Go to original source... Go to PubMed...
  21. Gupta, S.K., Bansal, P., Bhardwaj, R.K., Jaiswal, J., Velpandian, T., 2002. Comparison of analgesic and anti-inflammatory activity of meloxicam gel with diclofenac and piroxicam gels in animal models: pharmacokinetic parameters after topical application. Skin Pharmacol. Appl. Skin Physiol. 15, 105-111. Go to original source... Go to PubMed...
  22. Henriques, M.G., Rae, G.A., Cordeiro, R.S., Williams, T.J., 1992. Endothelin-1 inhibits PAF-induced paw oedema and pleurisy in the mouse. Br. J. Pharmacol. 106, 579-582. Go to original source... Go to PubMed...
  23. Ianiski, F.R., Alves, C.B., Souza, A.C.G., Pinton, S., Roman, S.S., Rhoden, C.R.B., Alves, M.P., Luchese, C., 2012. Protective effect of meloxicam-loaded nanocapsules against amyloid-b peptide-induced damage in mice. Behav. Brain Res. 230, 100-107. Go to original source... Go to PubMed...
  24. Impellizzeri, D., Esposito, E., Mazzon, E., Paterniti, I., Di Paola, R., Bramanti, P., Morittu, V.M., Procopio, A., Britti, D., Cuzzocrea, S., 2011. The effects of oleuropeinaglycone, an olive oil compound, in a mouse model of carrageenan-induced pleurisy. Clin. Nutr. 30, 533-540. Go to original source... Go to PubMed...
  25. Khachane, P., Date, A.A., Nagarsenker, M.S., 2011. Positively charged polymeric nanoparticles: application in improving therapeutic efficacy of meloxicam after oral administration. DiePharmazie 66, 334-338.
  26. Khurana, S., Jain, N.K., Bedi, P.M.S., 2013a. Development and characterization of a novel controlled release drug delivery system based on nanostructured lipid carriers gel for meloxicam. Life Sci. 93, 763-772. Go to original source... Go to PubMed...
  27. Khurana, S., Jain, N.K., Bedi, P.M.S., 2013b. Nanoemulsion based gel for transdermal delivery of meloxicam: physicochemical, mechanistic investigation. Life Sci. 92, 383-392. Go to original source... Go to PubMed...
  28. Kulhari, H., Pooja, D., Shrivastava, S., VGM, N., Sistla, R., 2014. Peptide conjugated polymeric nanoparticles as a carrier for targeted delivery of docetaxel. Colloids Surf. B: Biointerfaces 117, 166-173. Go to original source... Go to PubMed...
  29. Lapa, F.R., Da Silva, M.D., Cabrini, D.A., Santos, A.R.S., 2012. Antiinflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors. Purinergic Signal. 8, 693-704. Go to original source... Go to PubMed...
  30. Lee, P., Zhang, R., Li, V., Liu, X., Sun, R.W.Y., Che, C.M., Wong, K. K.Y., 2012. Enhancement of anticancer efficacy using modified lipophilic nanoparticle drug encapsulation. Int. J. Nanomed. 7, 731-737. Go to original source... Go to PubMed...
  31. Luchese, C., Prigol, M., Duarte, M.M.M.F., Nogueira, C.W., 2012. Diphenyldiselenide reduces inflammation in the mouse model of pleurisy induced by carrageenan: reduction of pro-inflammatory markers and reactive species levels. Inflamm. Res. 61, 1117-1124. Go to original source... Go to PubMed...
  32. Mazario, J., Gaitan, G., Herrero, J.F., 2001. Cyclooxygenase-1 vs. cyclooxygenase-2 inhibitors in the induction of antinociception in rodent withdrawal reflexes. Neuropharmacology 40, 937-946. Go to original source... Go to PubMed...
  33. Merisko-Liversidge, E.M., Liversidge, G.G., 2008. Drug nanoparticles: formulating poorly water-soluble compounds. Toxicol. Pathol. 36, 43-48. Go to original source... Go to PubMed...
  34. Moghimi, S.M., Hunter, A.C., Murray, J.C., 2005. Nanomedicine: current status and future prospects. FASEB J. 19, 311-330. Go to original source... Go to PubMed...
  35. Mora-Huertas, C.E., Fessi, H., Elaissari, A., 2010. Polymer-based nanocapsules for drug delivery. Int. J. Pharm. 385, 113-142. Go to original source... Go to PubMed...
  36. Oliveira, C., Navarro-Xavier, R.A., Anjos-Vallota, E.A., Martins, J. O., Silveira, V.L.F., Gonçalves, L.R.C., Araújo, M.S., Motta, G., Sannomiya, P., Oliva, M.L.V., 2010. Effect of plant neutrophil elastase inhibitor on leuocyte migration, adhesion and cytokine release in inflammatory conditions. Br. J. Pharmacol. 161, 899-910. Go to original source... Go to PubMed...
  37. Pairet, M., Van Ryn, J., Schierok, H., Mauz, A., Trummlitz, G., Engelhardt, G., 1998. Differential inhibition of cyclooxygenase-1 and-2 by meloxicam and its 4-isomer. Inflamm. Res. 47, 270-276. Go to original source... Go to PubMed...
  38. Paul, E.L., Lunardelli, A., Caberlon, E., de Oliveira, C.B., Santos, R. C., Biolchi, V., Bastos, C.M., Moreira, K.B., Nunes, F.B., Gosmann, G., de Oliveira, J.R., 2009. Anti-inflammatory and immunomodulatory effects of Baccharistrimera aqueous extract on induced pleurisy in rats and lymphoproliferation in vitro. Inflammation 32, 419-425. Go to original source... Go to PubMed...
  39. Rao, J.P., Geckeler, K.E., 2011. Polymer nanoparticles: preparation techniques and size - control parameters. Prog. Polym. Sci. 36, 887-913. Go to original source...
  40. Sakata, S., Uchida, K., Kaetsu, I., Kita, Y., 2007. Programming control of intelligent drug releases in response to single and binary environmental stimulation signals using sensor and electroresponsive hydrogel. Radiat. Phys. Chem. 76, 733-737. Go to original source...
  41. Saleh, T.S.F., Calixto, J.B., Medeiros, Y.S., 1999. Effects of antiinflammatorydrugs upon nitrate and myeloperoxidase levels in the mouse pleurisy induced by carrageenan. Peptides 20, 949-956. Go to original source... Go to PubMed...
  42. Seedher, N., Bhatia, S., 2005. Mechanism of interaction of the nonsteroidal antiinflammatory drugs meloxicam and nimesulida with serum albumin. J. Pharm. Biomed. Anal. 39, 257-262. Go to original source... Go to PubMed...
  43. Talero, E., Di Paola, R., Mazzon, E., Emanuela, E., Motilva, V., Cuzzocrea, S., 2012. Anti-inflammatory effects of adrenomedullin on acute lung injury induced by carrageenan in mice. Mediators Inflamm. 2012, 1-13. Go to original source... Go to PubMed...
  44. Tsai, M., Chien, C.F., Lin, L.C., Tsai, T.H., 2011. Curcumin and its nano-formulation: the kinetics of tissue distribution and blood-brain barrier penetration. Int. J. Pharm. 416, 331-338. Go to original source... Go to PubMed...
  45. Utsunomiya, I., Ito, M., Oh-ishi, S., 1998. Generation of inflammatory cytokines production in zymosan-induced pleurisy in rats: TNF induces IL-6 and cytokine-induced neutrophil chemoattractant (CICN) in vivo. Cytokine 10, 956-963. Go to original source... Go to PubMed...
  46. Van-Antwerpen, P., Neve, J., 2004. In vitro comparative assessment of the scavenging activity against three reactive oxygen species of non-steroidal anti-inflammatory drugs from the oxicam and sulfoanilide families. Eur. J. Pharmacol. 96, 55-61. Go to original source... Go to PubMed...
  47. Villalba, B.T., Ianiski, F.R., Wilhelm, E.A., Fernandes, R.S., Alves, M.P., Luchese, C., 2014. Meloxicam-loaded nanocapsules have antinociceptive and antiedematogenic effects in acute models of nociception. Life Sci. 115, 36-43. Go to original source... Go to PubMed...
  48. Zhao, L., Tao, J.Y., Zhang, S.L., Pang, R., Jin, F., Dong, J.H., Guo, Y. J., 2007. Inner anti-inflammatory mechanisms of petroleum ether extract from Melilotus suaveolens Ledeb. Inflammation 30, 213-223. Go to original source... Go to PubMed...