EFFECT OF SILYMARIN PARTICLE SIZE ON ITS SOLUBILITY AND ORAL BIOAVAILABILITY, THE ENHANCEMENT OF PHARMACOLOGICAL ACTIONS
Main Article Content
Keywords
silymarin nanoparticles, hepatoprotection, hepatic histopathology, albumin and protein values
Abstract
Due to the many side effects associated with conventional medicine, people turned their attention towards natural drugs, which have fewer or no side effects. However, their uses are restricted due to lower solubility and bioavailability. Plant-based nanoparticles have been demonstrated as more effective alternatives, and nanoparticles are reported to increase the bioavailability and solubility of natural medicines to make their better use. The nanotechnology system is innovative to enhance the therapeutic effects and bioavailability of naturally occurring drugs. Therefore, silymarin nanoparticles were prepared using two different methods. Characterization analysis confirmed the reduction in particle size and conversion to amorphous states. The achieved nanoparticles have the required size, optimum zeta potential, and PDI. Results from solubility and bioavailability studies are very encouraging. The prepared nanoparticles were tested for hepatoprotection; they proved better than the unprocessed drug in terms of better effects on hepatic marker enzymes, serum total albumin and protein values, and hepatic histopathology. The prepared nano drug is recommended for clinical trials.
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12. Shakya AK. Drug-induced hepatotoxicity and hepatoprotective medicinal plants: a review. Indian Journal of Pharmaceutical Education and Research, 54(2), 234-50 (2020).
13. Marmouzi I, Bouyahya A, Ezzat SM, El Jemli M, Kharbach M. The food plant Silybum marianum (L.) Gaertn.: Phytochemistry, Ethnopharmacology, and clinical evidence. Journal of Ethnopharmacology, 265, 113303-113303 (2021).
14. Adetuyi BO, Omolabi FK, Olajide PA, Oloke JK. Pharmacological, biochemical and therapeutic potential of milk thistle (silymarin): a review. World News of Natural Sciences, 37(2021), 75-91 (2021).
15. Giustarini D, Milzani A, Dalle-Donne I, Rossi R. How to Increase Cellular Glutathione. Antioxidants, 12(5), 1-20 (2023).
16. Samee A, Amir RM, Ahmad A, Watto FM, Ali M, Azam MT, Sheeraz M, Fatima H, Zahoor Z, Zahid M, Ashraf H. Effectiveness of Milk Thistle on Human Body against Diseases: A Comprehensive Review. Scholars Bulletin, 9(2), 8-18 (2023).
17. Assis-Júnior EM, Melo AT, Pereira VB, Wong DV, Sousa NR, Oliveira CM, Malveira LR, Moreira LS, Souza MH, Almeida PR, Lima-Júnior RC. Dual effect of silymarin on experimental non- alcoholic steatohepatitis induced by irinotecan. Toxicology and Applied Pharmacology, 327(2017), 71-9 (2017).
18. Mangwani N, Singh PK, Kumar V. Medicinal plants: adjunct treatment to tuberculosis chemotherapy to prevent hepatic damage. Journal of Ayurveda and Integrative Medicine, 11(4), 522- 28 (2020).
19. Kheong CW, Mustapha NR, Mahadeva S. A randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis. Clinical Gastroenterology and Hepatology. 2017 Dec 1;15(12):1940-9.
20. Colletta C, Colletta A, Placentino G. Lifestyle and silymarin: a fight against liver damage in NAFLD associated-prediabetic disease. Journal of Diabetes & Metabolic Disorders, 19(2020), 883- 94 (2020).
21. Curcio A, Romano A, Cuozzo S, Di Nicola A, Grassi O, Schiaroli D, Nocera GF, Pironti M. Silymarin in combination with vitamin C, vitamin E, coenzyme Q10 and selenomethionine to improve liver enzymes and blood lipid profile in NAFLD patients. Medicina, 56(10), 544 (2020).
22. Beydilli H, Yilmaz N, Cetin ES, Topal Y, Celik OI, Sahin C, Topal H, Cigerci IH, Sozen H. Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free- radical damage in rat liver. Iranian Red Crescent Medical Journal, 17(4), e25310 (2015).
23. Shriram RG, Moin A, Alotaibi HF, Khafagy ES, Al Saqr A, Abu Lila AS, Charyulu RN. Phytosomes as a plausible nano-delivery system for enhanced oral bioavailability and improved hepatoprotective activity of silymarin. Pharmaceuticals, 15(7), 790-809 (2022).
24. El-Far M, Salah N, Essam A, Abd El-Azim AO, El-Sherbiny IM. Silymarin nanoformulation as a potential anticancer agent in experimental Ehrlich ascites carcinoma-bearing animals. Nanomedicine, 13(15), 1865-58 (2018).
25. Anushiravani A, Haddadi N, Pourfarmanbar M, Mohammadkarimi V. Treatment options for nonalcoholic fatty liver disease: a double-blinded randomized placebo-controlled trial. European journal of gastroenterology & hepatology, 31(5), 613-7 (2019).
26. Wang X, Zhang Z, Wu SC. Health benefits of Silybum marianum: Phytochemistry, pharmacology, and applications. Journal of agricultural and food chemistry, 68(42), 11644-64 (2020).
27. Zhu HJ, Brinda BJ, Chavin KD, Bernstein HJ, Patrick KS, Markowitz JS. An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metabolism and Disposition. 2013 Sep 1;41(9):1679-85.
28. Hosseini S, Rezaei S, Moghaddam MR, Elyasi S, Karimi G. Evaluation of oral nano-silymarin formulation efficacy on prevention of radiotherapy-induced mucositis: A randomized, double- blinded, placebo-controlled clinical trial. PharmaNutrition, 15(2021), 100253 (2021).
29. Sher M, Zahoor M, Shah SW, Khan FA. Is particle size reduction linked to drug efficacy: an overview into nano initiatives in Pharmaceuticals. Zeitschrift für Physikalische Chemie. 2023 Jun 2(0).
30. Khan FA, Zahoor M, Islam NU, Hameed R. Synthesis of Cefixime and Azithromycin Nanoparticles. Journal of Nanomaterials, 2016, 29-37 (2016).
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Nov 21, 2023
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Mujahid Sher, Ishtiaq Hussain, Farhat Ali Khan, Hamid Hussain Afridi, Wiaam Mujahid Sher, Naila Gulfam, Muhammad Saqib Khalil, Akhtar Aman, Muhammad Sulaiman, & Zeeshan Ahmad. (2023). EFFECT OF SILYMARIN PARTICLE SIZE ON ITS SOLUBILITY AND ORAL BIOAVAILABILITY, THE ENHANCEMENT OF PHARMACOLOGICAL ACTIONS. Journal of Population Therapeutics and Clinical Pharmacology, 30(18), 2527–2560. https://doi.org/10.53555/jptcp.v30i18.3484
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Author Biographies
Mujahid Sher
Department of Pharmacy, Abbottabad University of Science and Technology, Abbottabad, Pakistan. Orcid.org/0000-0002-4594-9821.
Ishtiaq Hussain
Department of Pharmacy, Abbottabad University of Science and Technology, Abbottabad, Pakistan.
Farhat Ali Khan
Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir Upper 18000, Pakistan.
Hamid Hussain Afridi
Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir Upper 18000, Pakistan.
Wiaam Mujahid Sher
Khyber Medical College, KP, Pakistan
Naila Gulfam
Jinnah College for Women, University of Peshawar, KP, Pakistan
Muhammad Saqib Khalil
Sarhad University of Information Technology, Peshawar, Pakistan;
Akhtar Aman
Department of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir Upper 18000, Pakistan.
Muhammad Sulaiman
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing China.
Zeeshan Ahmad
Department of Microbiology, Hazara University Manshera, Pakistan