FORMULATION AND CHARACTERIZATION OF DICLOFENAC SODIUM LOADED PLGA NANOPARTICLES FOR INFLAMMATORY DISEASES AND IN-VIVO HET-CAM ANALYSIS
Main Article Content
Keywords
Anti-inflammatory, Diclofenac sodium, Drug delivery System, HET-CAM assay, Nanomedicine, Nanoparticle, PLGA
Abstract
The development of a new drug active substance is not only time-consuming and expensive, but also a chain of operations that often fails. However, increasing the bioavailability, effectiveness, safety, or targeting the drugs used in clinic by various methods, such as nanoparticles (NPs), may be a more effective way of using them in clinic. In addition, nanoparticle formulations are becoming increasingly popular in modern medical treatments. Angiogenesis, formation of new capillaries from a pre-existing one, fundamentally occurs in physiological processes such as wound healing, embryogenesis and menstrual cycle, also has a vital role in pathology of cancer, psoriasis, diabetic retinopathy and chronic inflammation. The Hen‟s Egg Test on the Chorioallantoic Membrane (HET-CAM) assay is a useful, well established and animal alternative in vivo procedure for evaluation of anti-inflammatory potentials and anti-irritant properties of nano drug delivery systems. In this study, diclofenac sodium (DS) loaded PLGA NPs were prepared and characterized. The particle size (PS) of DS-loaded PLGA NPs was between 114.7 and 124.8 nm and all NPs were monodisperse with negative zeta potential values. The encapsulation efficiency was in range of 41.4-77.8%. In vitro dissolution studies of NPs showed up to 24 h of DS release after the first 3 h of burst effect. The 3 h burst effect and 24 h release kinetics studied with DDSolver were found to be predominantly driven not only by one mechanism, by a combined mechanism of Fickian and non-Fickian. Solid state structures of formulations were clarified by DSC and FT-IR analysis. PS, EE% and release rates were found to be affected by the amount of DS added to the formulations. Increasing the amount of DS added to the formulations increased PS, while the EE% decreased. The release rates were affected by PS and the formulation with the lowest PS value showed slower release. The anti-inflammatory activity of optimum formulation (NP-1) was examined using in vivo HET- CAM assay. The anti-inflammatory activity results indicated that NP-1 coded NP formulation showed significantly good anti-inflammatory potential at low dose. As a result, a low dose high anti-inflammatory effect was achieved with the NP structure of DS. To the best of our knowledge this is the first study on in vivo anti-inflammatory activities of DS loaded PLGA NPs.
References
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13. Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., Zhao, L., 2018. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 9 (6), 7204-7218.
14. Chereddy, K.K., Her, C.H., Comune, M., Moia, C., Lopes, A., Porporato, P.E., Vanacker, J., Lam, M.C., Steinstraesser, L., Sonveux, P., Zhu, H., Ferreira, L.S., Vandermeulen, G., Preat, V., 2014. PLGA nanoparticles loaded with host defense peptide LL37 promote wound healing. J. Control. Release. 194, 138-147.
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16. Dalpiaz, A., Sacchetti, F., Baldisserotto, A., Pavan, B., Maretti, E., Iannuccelli, V., Leo, E., 2016. Application of the “in-oil nanoprecipitation” method in the encapsulation of hydrophilic drugs in PLGA nanoparticles. J. Drug. Deliv. Sci. Technol. 32, 283-290.
17. Davoudi, Z., Peroutka-Bigus, N., Bellaire, B., Wannemuehler, M., Barrett, T.A., Narasimhan, B., Wang, Q., 2017. Intestinal organoids containing poly(lactic‐co‐glycolic acid) nanoparticles for the treatment of inflammatory bowel diseases. J. Biomed. Mater. Res. Part A. 106(4), 876-886.
18. Jesus Gomes, A., Lunardi, C.N., Caetano, F.H., Lunardi, L.O., da Hora Machado, A.E., 2006. Phagocytosis of PLGA microparticles in rat peritoneal exudate cells: a timedependent study. Microsc. Microanal. 12 (5), 399-405.
19. Lima, I.A., Khalil, N.M., Tominaga, T.T., Lechanteur, A., Sarmento, B., Mainardes, R.M., 2018. Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid. Artif. Cells Nanomed. B. 46, 993–1002.
20. Dhokale, K.K., Deore, D.D., Nagras, M.A., 2016. UV spectrophotometric method for simultaneous estimation of diclofenac salt and eperisone hydrochloride in bulk and capsule dosage form. Int. J. Pharm. Sci. Res. 7(9), 3810-3814.
21. Dinavard, R., Sepehri, N., Manoochehri, S., Rouhani, H., Atyabi, F., 2011. Polylactide-coglycolide nanoparticles for controlled delivery of anticancer agents. Int. J. Nanomed. 6, 877-895.
22. Elmaskaya, A., Öztürk, A.A., Büyükköroğlu, G., Yenilmez, E., 2019. Spray-dried Ketoprofen Lysine-incorporated PLGA Nanoparticles; Formulation, Characterization, Evaluation and Cytotoxic Profile. Indian J. Pharm. Sci. 81 (4), 640-650.
23. Fini, A., Bassini, G., Monastero, A., Cavallari, C., 2012. Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions. Pharmaceutics. 4(3), 413-429. https://doi.org/10.3390/pharmaceutics4030413
24. Fredenberg, S., Wahlgren, M., Reslow, M., Axelsson, A., 2011. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-a review. Int. J. Pharm. 415 (1-2), 34-52.
25. Fu,Y., Kao, W.J., 2010. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opin. Drug Deliv. 7 (4), 429-444.
26. Gamisans, F., Lacoulonche, F., Chauvet, A., Espina, M., Garcia, M.L., Egea, M.A., 1999. Flurbiprofen- loaded nanospheres: Analysis of the matrix structure by thermal methods. Int. J. Pharm. 179, 37-48.
27. Griffioen, A.W., Molema, G., 2000. Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacol. Rev. 52(2), 237-268.
28. Gu, Z., Aimetti, A.A., Wang, Q, Dang, T.T., Zhang, Y., Veiseh, O., Cheng, H., Langer, R.S., Anderson, D.G., 2013. Injectable Nano-Network for Glucose-Mediated Insulin Delivery. ACS Nano. 7(5), 4194-4201.
29. Gupta, H., Aqil, M., Khar, R. K., Ali, A., Bhatnagar, A., Mittal, G. 2011. Biodegradable levofloxacin nanoparticles for sustained ocular drug delivery. J. Drug Target. 19(6), 409-417.
30. Hou, D., Gui, R., Hu, S., Huang, Y., Feng, Z., Ping, Q., 2015. Preparation and characterization of novel drug-inserted-montmorillonite chitosan carriers for ocular drug delivery. ANP. 4, 70-84.
31. Jain, R.A., 2000. The manufacturing techniques of various drug loaded biodegradable poly Khanal, S., Adhikari, U., Rijal, N., Bhattarai, S., Sankar, J., Bhattarai, N., 2016. pH-responsive PLGA nanoparticle for controlled payload delivery of diclofenac sodium. J. Funct. Biomater. 7(3), 21.
32. Kim, Y., West, X.Z., Byzova, T.V., 2013. Inflammation and oxidative stress in angiogenesis and vascular disease. J. Mol. Med. (Berl). 91(3), 323-328.
33. Kıyan, H.T., 2010. Bazı Hypericum türlerinin uçucu yağ bileşimleri ve antianjiyojenik aktiviteleri. Master thesis, Institute of Health Sciences, Department of Pharmacognosy, Eskişehir, Turkey.
34. Krenn, L., Paper, D.H., 2009. Inhibition of angiogenesis and inflammation by an exract of red clover (Trifolium pratense L.). Phytomedicine. 16, 1083-1088.
35. Kumar Sahu, R., Singh, B., Saraf, S.A., Kaithwas, G., Kishor, K., 2014. Photochemical toxicity of drugs intended for ocular use. Arh. Hig. Rada. Toksikol. 65(2), 157-167.
36. Kumar, R., Sinha, V.R., 2016. Solid lipid nanoparticle: an efficient carrier for improved ocular permeation of voriconazole. Drug. Dev. Ind. Pharm. 42(12), 1956-1967.
37. Liang, X.X., Omer, A.M., Hu, Z.H., Wang, Y.G., Yu, D., Ouyang, X.K., 2019. Efficient adsorption of diclofenac sodium from aqueous solutions using magnetic aminefunctionalized chitosan. Chemosphere. 217, 270-278.
38. Mainardes, R.M., Evangelista, R.C., 2005. PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. Int. J. Pharm. 290 (1-2), 137-144.
39. Mainardes, R.M., Gremião, M.P.D., Evangelista, R.C., 2006. Thermoanalytical study of praziquantel-loaded PLGA nanoparticles. Rev. Bras. Cienc. Farm. 42(4), 523-530.
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Mar 12, 2023
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How to Cite
Sheetal Mishra, Ankita Damahe, Divya Sahu, Chandrika Ahirwal, Lumeshwari, Preeti Maravi, & Jhakeshwar Prasad. (2023). FORMULATION AND CHARACTERIZATION OF DICLOFENAC SODIUM LOADED PLGA NANOPARTICLES FOR INFLAMMATORY DISEASES AND IN-VIVO HET-CAM ANALYSIS. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 949-966. https://doi.org/10.53555/jptcp.v30i3.3587
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Author Biographies
Sheetal Mishra
Shri Shankaracharya Institute of Pharmaceutical Sciences and Research, Junwani – 490020, Bhilai, Chhattisgarh, India
Ankita Damahe
Apollo College of Pharmacy, Durg – 491001, Chhattisgarh, India
Divya Sahu
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur – 492010, Chhattisgarh, India
Chandrika Ahirwal
Faculty of Pharmacy, Chandkhuri, Durg – 491221, Chhattisgarh, India
Lumeshwari
Bharti Vishwavidyalaya, Durg – 491001, Chhattisgarh, India
Preeti Maravi
Bharti Vishwavidyalaya, Durg – 491001, Chhattisgarh, India
Jhakeshwar Prasad
Shri Shankaracharya College of Pharmaceutical Sciences, Junwani – 490020, Bhilai, Chhattisgarh, India
How to Cite
Sheetal Mishra, Ankita Damahe, Divya Sahu, Chandrika Ahirwal, Lumeshwari, Preeti Maravi, & Jhakeshwar Prasad. (2023). FORMULATION AND CHARACTERIZATION OF DICLOFENAC SODIUM LOADED PLGA NANOPARTICLES FOR INFLAMMATORY DISEASES AND IN-VIVO HET-CAM ANALYSIS. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 949-966. https://doi.org/10.53555/jptcp.v30i3.3587