PRODUCTION OF GANODERMA LUCIDUM EXTRACT LOADED GELATIN-SODIUM ALGINATE MICROSPHERES, INVESTIGATION OF RELEASE KINETICS AT DIFFERENT pH VALUES AND EVALUATION OF KINETIC MODELS

Öz

In this study, pH sensitive microsphere polymeric drug carriers were produced by using biodegradable natural gelatin and sodium alginate polymers. Microspheres were loaded with prepared Ganoderma lucidum extract that is a medicinal mushroom and has the potential to be used in several diseases’ treatment. Extract release kinetics of the microspheres were examined by spectrophotometric method by using an UV spectrometer. Buffer solutions with different pH values were used as release medium for examination of drug release kinetics of the produced microspheres. The Ganoderma lucidum release of microspheres was presented in terms of percent cumulative release (CR%) defined as the percentage ratio of the instantaneous amount of Ganoderma lucidum released at a certain time of incubation to the initial amount of Ganoderma lucidum loadings. As a result, it was seen that the release of the extract accelerated as pH of the release medium increased and the fastest extract release was observed in the pH 7. The release kinetic models of the microspheres were examined. The release kinetics of microspheres fitted Higuchi model for pH 1.3, pH 5.0 and pH 6.0 and first-order model for pH 3.0 and pH 7.0.

Anahtar Kelimeler

• Ganoderma lucidum
• drug carrier
• controlled release
• pH sensitive polymer
• kinetic release model

Kaynakça

1. Gao, Y., Zhou, S., Jiang, W., Huang, M. and Dai, X., “Effects of Ganopoly®(A Ganoderma lucidum polysaccharide extract) on the immune functions in Advanced‐Stage cancer patients”, Immunological Investigations, 32(3), 201-215, 2003.
2. Mau, J. L., Lin, H. C., and Chen, C. C., “Non-volatile components of several medicinal mushrooms”, Food Research International, 34(6), 521-526, 2001.
3. Yuen, J. W. and Gohel, M. D. I., “Anticancer effects of Ganoderma lucidum: a review of scientific evidence”, Nutrition and Cancer, 53(1), 11-17, 2005.
4. Zhou, X., Lin, J., Yin, Y., Zhao, J., Sun, X. and Tang, K., “Ganodermataceae: natural products and their related pharmacological functions”, The American journal of Chinese medicine, 35(04), 559-574, 2007.
5. Thyagarajan, A., Jedinak, A., Nguyen, H., Terry, C., Baldridge, L. A., Jiang, J., Sliva, D., “Triterpenes from Ganoderma Lucidum induce autophagy in colon cancer through the inhibition of p38 mitogen-activated kinase”, Nutrition and Cancer, 62(5), 630-640, 2010.
6. Fukuzawa, M., Yamaguchi, R., Hide, I., Chen, Z., Hirai, Y., Sugimoto, A., Nakata, Y., “Possible involvement of long chain fatty acids in the spores of Ganoderma lucidum (Reishi Houshi) to its anti-tumor activity”, Biological and Pharmaceutical Bulletin, 31(10), 1933-1937. 2008.
7. Wu, D. T., Xie, J., Hu, D. J., Zhao, J., Li, S. P., “Characterization of polysaccharides from Ganoderma spp. using saccharide mapping”, Carbohydrate Polymers, 97(2), 398-405, 2013.
8. Vasir, J. K., Tambwekar, K. and Garg, S., “Bioadhesive microspheres as a controlled drug delivery system”, International Journal of Pharmaceutics, 255(1-2), 13-32, 2003.

9. Dortunç, B. (A. Gürsoy) Kontrollu Salım Sistemleri; Kolona İlaç Taşıyan Sistemler, Elma Bilgisayar Basım ve Ambalaj San. Tic. Ltd. Şti., İstanbul, (p.283–297, ISBN:975–97725–0–7), 2002.
10. Hashida, M., Takahashi, Y., Muranishi, S., Sezaki, H., “An application of water-in-oil and gelatin-microsphere-in-oil emulsions to specific delivery of anticancer agent into stomach lymphatics”, Journal of Pharmacokinetics and Biopharmaceutics, 5(3), 241-255, 1977.
11. İskenderoğlu, C, “Düşük molekül ağırlıklı heparinin oral ilaç şekli üzerine çalışmalar” (Doctoral dissertation, Doktora Tezi (Danışman: Prof. Dr. F. Acartürk), Gazi Üniversitesi, Sağlık Bilimleri Enstitüsü, Ankara), 2007.
12. Yao, Z. C., Jin, L. J., Ahmad, Z., Huang, J., Chang, M. W., Li, J. S., “Ganoderma lucidum polysaccharide loaded sodium alginate micro-particles prepared via electrospraying in controlled deposition environments”, International Journal of Pharmaceutics, 524(1-2), 148-158, 2017.
13. Gong, R., Li, C., Zhu, S., Zhang, Y., Du, Y., Jiang, J., “A novel pH-sensitive hydrogel based on dual crosslinked alginate/N-α-glutaric acid chitosan for oral delivery of protein”, Carbohydrate Polymers, 85(4), 869-874, 2011.
14. Wang, Q., Wang, W., Wu, J., & Wang, A., “Effect of attapulgite contents on release behaviors of a pH sensitive carboxymethyl cellulose‐g‐poly (acrylic acid)/attapulgite/sodium alginate composite hydrogel bead containing diclofenac”, Journal of Applied Polymer Science, 124(6), 4424-4432, 2012.
15. Colinet, I., Dulong, V., Mocanu, G., Picton, L., Le Cerf, D., “Effect of chitosan coating on the swelling and controlled release of a poorly water-soluble drug from an amphiphilic and pH-sensitive hydrogel”. International journal of biological macromolecules, 47(2), 120-125, 2010.
16. Wang, S., Zhang, Q., Tan, B., Liu, L., Shi, L., “pH-sensitive poly (vinyl alcohol)/sodium carboxymethylcellulose hydrogel beads for drug delivery”, Journal of Macromolecular Science, Part B, 50(12), 2307-2317, 2011.
17. Banerjee, S., Singh, S., Bhattacharya, S. S., Chattopadhyay, P., “Trivalent ion cross-linked pH sensitive alginate-methyl cellulose blend hydrogel beads from aqueous template”, International journal of biological macromolecules, 57, 297-307, 2013.
18. Yang, B., Lu, Y., Ren, T., Luo, G., “One-step synthesis of pH-sensitive poly (Acrylamide-co-Sodium Acrylate) beads with core–shell structure”, Reactive and Functional Polymers, 73(1), 122-131, 2013.
19. Eldin, M. S. M., Kamoun, E. A., Sofan, M. A., Elbayomi, S. M., “L-Arginine grafted alginate hydrogel beads: A novel pH-sensitive system for specific protein delivery”, Arabian Journal of Chemistry, 8(3), 355-365, 2015.
20. Li, L., Dong, C., Liu, L., Li, J., Xiao, K., Zhang, D., Li, X., “Preparation and characterization of pH-controlled-release intelligent corrosion inhibitor”, Materials Letters, 116, 318-321, 2014.
21. Elmas, A., Akyüz, G., Bergal, A., Andaç, M., Andaç, Ö., “Mathematical Modelling of Drug Release”, Res. Eng. Struct. Mater., 6(4): 327-350, 2020.
22. Alhalmi, A., Altowairi, M, Saeed, O., Alzubaidi, N., Almoiliqy, M., Abdulmalik, W., “Sustained Release Matrix System: An Overwiew”, World Journal Of Pharmacy And Pharmaceutıcal Scıences, 7-6, 1470-1486.
23. Dash, S., Murthy, P.N., Nath, L., Chowdhury, P., “Kinetic modeling on drug release from controlled drug delivery systems”, Acta Poloniae Pharmaceutica in Drug Research, 67-3, 217-223, 2010.
24. Singhvi, G., Singh, M., “Review: In-Vitro Drug Release Characterization Models”, International Journal of Pharmaceutical Studies and Research, 2-1, 77-84, 2011.
25. Paarakh, M., P., Jose, P.A., Setty, C. M., Chrıstoper, G.V.P., “Release Kınetıcs – Concepts and Applıcatıons”, International Journal of Pharmacy Research & Technology,8, 12-20, 2018.
26. Pastuszka, K.Do.W., Krzak, J., Macikowski, B., Berkowski, R., Osinski, B., Musiał, W. “Evaluation of the Release Kinetics of a Pharmacologically Active Substance from Model Intra-Articular Implants Replacing the Cruciate Ligaments of the Knee”, Materials, 12, 1202, 2019.