Syed Abdul Azeez, Afreen Sultana, Amtul Hajera
Prof. Dr. Syed Abdul Azeez, Afreen Sultana*, Amtul Hajera
Department of Pharmaceutics, Deccan School of Pharmacy, Affiliated to Osmania University, Dar-Us-Salam, Aghapura, Hyderabad - 500001, Telangana-India.
Volume - 12,
Issue - 4,
Year - 2022
Sodium alginate (SA)-based ß-cyclodextrin(ß-CD) can show an amazing adsorption capacity and are considered as secure and biocompatible frameworks for evacuating harmful particles from the body. Tyrosine, an amino acid which is found in certain nourishment and food constituents is changed over into p-Cresyl sulfate by intestine microbiota and on the off chance that this cannot be evacuated from the body, it will come-up as a dangerous uremic toxin in the body and rapid removal of this toxic molecule is relevant especially for patients affected by chronic kidney disease. Based on the necessity in the removal of this protein bound uremic toxin, Innovative cyclodextrin polymers were synthesized with different concentrations of sodium alginate to form nanosponges which are able to remove p-Cresol (Phenolic molecule), before it converted into the toxic form i,e,. p-Cresyl sulfate in the body. Furthermore, in vitro studies were carried out using optimal concentrations of sodium alginate with ß-cyclodextrin-NS formulations by assessing physicochemical properties, stability, phenol adsorption capacity and in vitro toxicity. Nanosponges (NSs) were found to be of 1:2 proportion of ß-cyclodextrin with sodium alginate respectively as NS2-formulation with an adsorption efficiency of in-vitro phenol toxin is 72%. In contrast, this subsidiary was more-steady in gastrointestinal media. In conclusion, this idea proposes that CD-NS details are secure and successful in expelling harmful atoms from the body. Their potential utilization in veterinary or human medication may diminish dialysis recurrence and lead to decreased phenol arrangement which concurrently decreases the cardiovascular and renal burden.
Cite this article:
Syed Abdul Azeez, Afreen Sultana, Amtul Hajera. β-Cyclodextrin with Sodium Alginate based Nanosponges Preparation and Characterization in the Removal of Organic Toxin: p-Cresol in the Simulated Biological Fluids. Asian Journal of Research in Pharmaceutical Sciences. 2022; 12(4):261-1. doi: 10.52711/2231-5659.2022.00045
Syed Abdul Azeez, Afreen Sultana, Amtul Hajera. β-Cyclodextrin with Sodium Alginate based Nanosponges Preparation and Characterization in the Removal of Organic Toxin: p-Cresol in the Simulated Biological Fluids. Asian Journal of Research in Pharmaceutical Sciences. 2022; 12(4):261-1. doi: 10.52711/2231-5659.2022.00045 Available on: https://ajpsonline.com/AbstractView.aspx?PID=2022-12-4-1
1. Go, A.S., Chertow, G.M., Fan, D., McCulloch, C.E., Hsu, C.-Y., 2004. Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and Hospitalization. N. Engl. J. Med. 351, 1296–1305.
2. Hill, N.R., Fatoba, S.T., Oke, J.L., Hirst, J.A., O’Callaghan, C.A., Lasserson, D.S Hobbs, F.D.R., 2016. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS ONE 11, e0158765.
3. Perlman, R.L., Finkelstein, F.O., Liu, L., Roys, E., Kiser, M., Eisele, G., Burrows-Hudson, S., Messana, J.M., Levin, N., Rajagopalan, S., Port, F.K., Wolfe, R.A., Saran, R., 2005. Quality of life in chronic kidney disease (CKD): a cross-sectional analysis in the Renal Research Institute-CKD study. Am. J. Kidney Dis. 45, 658–666.
4. GBD, 2017. Causes of Death Collaborators, 2018. Global, regional, and national age-sex- specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet 392, 1736–1788.
5. Kuehn BM. Excess Deaths From End-Stage Kidney Disease Early in Pandemic. JAMA. 2021;326(4):300.
6. Watanabe, Kimio; Watanabe, Tsuyoshi; Nakayama, Masaaki: Cerebro-renal interactions: Impact of uremic toxins on cognitive function. (2014) NeuroToxicology
7. Sun, C. Y.; Chang, S. C.; Wu, M. S.: Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. (2012)
8. Vanholder, Raymond; Schepers, Eva; Pletinck, Anneleen; Nagler, Evi V.; Glorieux, Griet: The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate: A Systematic Review. (2014) Journal of the American Society of Nephrology
9. Opdebeeck, B.; Maudsley, S.; Azmi, A.; De, Maré A.; De, Leger W.; Meijers, B. et al.: Indoxyl Sulfate and p-Cresyl Sulfate Promote Vascular Calcification and Associate with Glucose Intolerance. (2019) Journal of the American Society of Nephrology
10. Koppe, L.; Pillon, N. J.; Vella, R. E.; Croze, M. L.; Pelletier, C. C.; Chambert, S. et al.: p-Cresyl sulfate promotes insulin resistance associated with CKD. (2013) Journal of the American Society of Nephrology
11. Wong, Jakk; Piceno, Yvette M.; DeSantis, Todd Z.; Pahl, Madeleine; Andersen, Gary L.; Vaziri, Nosratola D.: Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. (2014) American journal of nephrology
12. Sankowski, Bartłomiej; Księżarczyk, Karolina; Rackowska, Emilia; Szlufik, Stanisław; Koziorowski, Dariusz; Giebułtowicz, Joanna: Higher cerebrospinal fluid to plasma ratio of p-cresol sulfate and indoxyl sulfate in patients with Parkinson’s disease. (2020) Clinica Chimica Acta
13. Gryp T, Vanholder R, Vaneechoutte M, Glorieux G. p-Cresyl Sulfate. Toxins (Basel). 2017;9(2):52. Published 2017 Jan 29.
14. Ananya, K., Preethi, S., Amit, B.P., Gowda, D., 2020. Recent review on Nano sponge. Int. J. Res. Pharm. Sci. 11, 1085–1096.
15. Hu, C.-M.J., Fang, R.H., Copp, J., Luk, B.T., Zhang, L., 2013. A biomimetic nanosponge that absorbs pore-forming toxins. Nat. Nanotechnol. 8, 336–340. ISO 10993-5, 2009. Biological evaluation of medical devices —Part 5: Tests for in vitro cytotoxicity.
16. Bilensoy, E., Hincal, A.A., 2009. Recent advances and future directions in amphiphilic cyclodextrin nanoparticles. Expert. Opin. Drug Del. 6, 1161–1173.
17. Kurkov, S.V., Loftsson, T., 2013. Cyclodextrins. 453, 167–180.
18. Varan, G., Varan, C., Erdoğar, N., Hıncal, A.A., Bilensoy, E., 2017. Amphiphilic cyclodextrin nanoparticles. Int. J. Pharm. 531, 457–469.
19. Carrier, R.L., Miller, L.A., Ahmed, I., 2007. The utility of cyclodextrins for enhancing oral bioavailability. 123, 78-99.
20. Hirayama, F., Uekama, K., 1999. Cyclodextrin-based controlled drug release system. Adv. Drug Deliv. Rev. 36, 125–141.
21. Loftsson, T., Brewster, M.E., 2011. Pharmaceutical applications of cyclodextrins: Effects on drug permeation through biological membranes. J. Pharm. Pharmacol. 63, 1119–1135.
22. Uekama, K., Hirayama, F., Irie, T., 1998. Cyclodextrin drug carrier systems. Chem. Rev. 98, 2045–2076.
23. Swaminathan, S., Cavalli, R., Trotta, F., 2016. Cyclodextrin-based nanosponges: a versatile platform for cancer nanotherapeutics development. WIREs Nanomed. Nanobiotechnol. 8, 579–601.
24. Trotta, F., Zanetti, M., Cavalli, R., 2012. Cyclodextrin-based nanosponges as drug carriers. Beilstein. J. Org. Chem. 8, 2091–2099.
25. Torne, S.J., Ansari, K.A., Vavia, P.R., Trotta, F., Cavalli, R., 2010. Enhanced oral paclitaxel bioavailability after administration of paclitaxel-loaded nanosponges. Drug Delivery 17, 419–425.
26. Torne, S., Darandale, S., Vavia, P., Trotta, F., Cavalli, R., 2013. Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery. Pharm. Dev. Technol. 18, 619–625.
27. Swaminathan, S., Pastero, L., Serpe, L., Trotta, F., Vavia, P., Aquilano, D., Trotta, M., Zara, G., Cavalli, R., 2010. Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity. Eur. J. Pharm. Biopharm. 74, 193–201.
28. Lembo, D., Swaminathan, S., Donalisio, M., Civra, A., Pastero, L., Aquilano, D., Vavia, P., Trotta, F., Cavalli, R., 2013. Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy. Int. J. Pharm. 443, 262–272.
29. Darandale, S.S., Vavia, P.R., 2013. Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. J. Incl. Phenom. Macro. 75, 315–322.
30. Swaminathan, S., Pastero, L., Serpe, L., Trotta, F., Vavia, P., Aquilano, D., Trotta, M., Zara, G., Cavalli, R., 2010. Cyclodextrin-based nanosponges encapsulating camptothecin: Physicochemical characterization, stability and cytotoxicity. Eur. J. Pharm. Biopharm. 74, 193–201.
31. Ansari, K.A., Vavia, P.R., Trotta, F., Cavalli, R., 2011. Cyclodextrin-Based Nanosponges for Delivery of Resveratrol. In Vitro Characterisation, Stability Cytotoxicity and Permeation Study. AAPS PharmSciTech 12, 279–286.
32. Cavalli, R., Akhter, A.K., Bisazza, A., Giustetto, P., Trotta, F., Vavia, P., 2010. Nanosponge formulations as oxygen delivery systems. Int. J. Pharm. 402, 254–257.
33. Mihailiasa, M., Caldera, F., Li, J., Peila, R., Ferri, A., Trotta, F., 2016. Preparation of functionalized cotton fabrics by means of melatonin loaded β-cyclodextrin nanosponges. Carbohydr Polym 142, 24–30.
34. Li, D., Ma, M., 1999. Nanosponges: From inclusion chemistry to water purifying technology. Chem. Tech. 29, 31–37.
35. Hu, C.-M.J., Fang, R.H., Copp, J., Luk, B.T., Zhang, L., 2013. A biomimetic nanosponge that absorbs pore-forming toxins. Nat. Nanotechnol. 8, 336–340. ISO 10993-5, 2009. Biological evaluation of medical devices —Part 5: Tests for in vitro cytotoxicity.
36. C. Varan, A. Anceschi, S. Sevli, N. Bruni, L. Giraudo, E. Bilgiç, P. Korkusuz, A.B. İskit, F. Trotta, E. Bilensoy, Preparation and Characterization of Cyclodextrin Nanosponges for Organic Toxic Molecule Removal, International Journal of Pharmaceutics (2020)
37. Preparation of Simulated Gastric Fluid, Bioscience Education [Internet], Available from :
38. https://bioscience-education.blogspot.com/2014/06/preparation-of-simulated-gastric-fluid.html?m=1, 20-June-2014.
39. Preparation of Simulated Intestinal Fluid, Bioscience Education [Internet], Available from:https://bioscience-education.blogspot.com/2014/06/preparation-of-simulated-intestinal.html?m=1 , 27-June-2014.
40. Electronic Supplementary Material (ESI) for Food & Function. This journal is © The Royal Society of Chemistry 2020. Available from : d0fo02319a1.pdf
41. Andi Sri, Suriati Amal et, al,. Preparation of Artificial Saliva Formulation, Research gate, October 2015.
42. Erika Stippler, Sabine Kopp, Jennifer B. Dressman et, al,. Comparison of US Pharmacopeia Simulated Intestinal Fluid TS (without pancreatin) and Phosphate Standard Buffer pH 6.8, TS of the International Pharmacopoeia with Respect to Their Use in In Vitro Dissolution Testing. May-2004.
43. Krstonošić, Milica Atanacković; Hogervorst, Jelena Cvejić; Mikulić, Mira; Gojković-Bukarica, Ljiljana. Development of HPLC method for determination of phenolic compounds on a core shell column by direct injection of wine samples. Acta Chromatographica, (), 1–5, Feb-2019.
44. Hard Gelatin Capsules: Formulation and Manufacturing Considerations [Internet], by Pharmapproach in Pharmaceutical Technology, Available from : https://www.pharmapproach.com/hard-gelatin-capsules-formulation-and-manufacturing-considerations/ : May 16- 2021.
45. Litou C, Vertzoni M, Goumas C, Vasdekis V, Xu W, Kesisoglou F, Reppas C. Characteristics of the human upper gastrointestinal contents in the fasted state under hypo- and A-chlorhydric gastric conditions under conditions of typical drug – drug interaction studies. Pharm Res 2016 Jun 14;33(6):1399–1412. Available from: http:// link.springer.com/10.1007/s11095-016-1882-8.
46. Crupi, V., Majolino, D., Mele, A., Melone, L., Punta, C., Rossi, B., Toraldo, F., Trotta, F., Venuti, V., 2014. Direct evidence of gel–sol transition in cyclodextrin-based hydrogels as revealed by FTIR-ATR spectroscopy. Soft Matter 10, 2320–2326.
47. N. M. Vageesh, Ramya Sri Sura, K Gulijar Begum, B Swathi. Formulation Development and In vitro Evaluation of Floating Tablets of Lafutidine by Employing Effervescent Technology. Asian J. Pharm. Res. 2017; 7(3): 189-197.
48. Shankar B. Kalbhare, Mandar J. Bhandwalkar, Rohit K. Pawar, Abhirup R. Sagre. Sodium Alginate cross-linked Polymeric Microbeads for oral Sustained drug delivery in Hypertension: Formulation and Evaluation. Asian J. Res. Pharm. Sci. 2020; 10(3):153-157.
49. Sampada V. Kadam, Nilima U. Rane, Chandrakant S. Magdum. Formulation and Evaluation of Orodispersible Tablets of Levamisole Hydrochloride. Asian J. Pharm. Tech. 2019; 9(2):63-68.
50. Priyanka V Dhalkar, Shivani S Jagtap, Suraj T Jadhav, Myuresh R. Redkar., Biradev S Karande. Formulation and Evaluation of in situ Gel Model Naproxen. Asian J. Pharm. Tech. 2019; 9(3):204-207.
51. Ashok Thulluru, S. Shakir Basha, C. Bhuvaneswara Rao, Ch. S. Phani Kumar, Nawaz Mahammed, K. Saravana kumar. Optimization of HPMC K100M and Sodium Alginate Ratio in Metronidazole Floating Tablets for the Effective Eradication of Helicobacter pylori. Asian J. Pharm. Tech. 2019; 9(3):195-203.
52. N. Sandhya Rani, M. Teja Krishna, V. Saikishore. . Design and Development of Sweet Potato Starch Blended Sodium Alginate Mucoadhesive Microcapsules of Glipizide. Research J. Pharma. Dosage Forms and Tech. 2012; 4(2): 119-123.
53. Megha B. Hiroji, Nagesh C., Devdatt Jani, Chandrashekhara S. Development and Evaluation of Transdermal Drug Delivery System using Natural Polysaccharides. Research J. Pharma. Dosage Forms and Tech. 2012; 4(5): 278-284.
54. LP Hingmire, VN Deshmukh, DM Sakarkar. LP Hingmire, VN Deshmukh, DM Sakarkar. Development and Evaluation of Sustained Release Matrix Tablets Using Natural Polymer as Release Modifier. Research J. Pharm. and Tech. 1(3): July-Sept. 2008; Page 193-196.
55. I Nyoman Suryadinata, Astina Putra, Tutiek Purwanti, Dewi Melani Hariyadi. Characterization of Microspheres in Alginate-Gelatin matrix with Ionotropic gelation method and Aerosolization Technique. Research J. Pharm. and Tech 2020; 13(9):4239-4243.
56. Sumit Kumar, Dinesh Chandra Bhatt. Influence of Sodium Alginate and Calcium Chloride on the Characteristics of Isoniazid Loaded Nanoparticles. Research J. Pharm. and Tech. 2021; 14(1):389-396.