Drug delivery system for controlled release of empagliflozin from alginate-chitosan nanocarrier system

A biocompatible nanocarrier system was prepared in this research through the reaction of calcium alginate (CA) with chitosan (CS). The structure of developed nanocarriers (CS-CA) was characterized by thermogravimetric analysis (TGA), Fourier transforms infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD) atomic force microscopy (AFM), and transmission electron microscopy (TEM). Swelling properties of CS-CA and CA, and their ability for loading and in vitro release of empagliflozin (EMP) were also investigated. The results showed the higher loading capacity of CS-CA compared to CA. For both nanocarriers, the drug release was higher at neutral pH (7.4 and 6.8) when compared to acidic pH (1.2). Despite the higher release of CA than CS-CA, the latter exhibited a favorable sustained drug release in all pH levels. As a result, CS-CA nanocarrier (EMP@CS-CANC) can be suggested as a new candidate for colon drug delivery of EMP.

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1. Rojas LB, Gomes MB. Metformin: an old but still the best treatment for type 2 diabetes. Diabetology & Metabolic Syndrome 2013; 5 (1): 1-5. doi: 10.1186/1758-5996-5-6
2. Zhu J, Zhong L, Chen W, Song Y, Qian Z et al. Preparation and characterization of pectin/chitosan beads containing porous starch embedded with doxorubicin hydrochloride: A novel and simple colon targeted drug delivery system. Food Hydrocolloids 2019; 95: 562-70. doi: 10.1016/j.foodhyd.2018.04.042
3. Englert C, Brendel JC, Majdanski TC, Yildirim T, Schubert S et al. US. Pharmapolymers in the 21st century: Synthetic polymers in drug delivery applications. Progress in Polymer Science 2018; 87: 107-64. doi: 10.1016/j.progpolymsci 2018.07.005
4 . Peng C, Huang Y, Zheng J. Renal clearable nanocarriers: Overcoming the physiological barriers for precise drug delivery and clearance. Journal of Controlled Release 2020; 322: 64-80. doi: 10.1016/j.jconrel .2020.03.020
5. Gadadare R, Mandpe L, Pokharkar V. Ultra rapidly dissolving repaglinide nanosized crystals prepared via bottom-up and top-down approach: influence of food on pharmacokinetics behavior. official journal of the American Association of Pharmaceutical Scientists 2015;16 (4): 787-99. doi: 10.1208/s12249-014-0267-8
6. Nie X, Chen Z, Pang L, Wang L, Jiang H et al. Oral Nano Drug Delivery Systems for the Treatment of Type 2 Diabetes Mellitus: An Available Administration Strategy for Antidiabetic Phytocompounds. International Journal of Nanomedicine 2020; 15: 10215. doi: 10.2147/IJN. S285134
7. Tong X, Pan W, Su T, Zhang M, Dong W et al. Recent advances in natural polymer-based drug delivery systems. Reactive and Functional Polymers 2020;148:104501. doi: 10.1016/ j.reactfunctpolym.2020.104501
8. Prajapati SK, Jain A, Jain A, Jain S. Biodegradable polymers and constructs: A novel approach in drug delivery. European Polymer Journal 2019; 120: 109191. doi: 10.1016/j.eurpolymj. 2019.08.018
9. Kumar S, Bhanjana G, Verma RK, Dhingra D, Dilbaghi N et al. Metformin-loaded alginate nanoparticles as an effective antidiabetic agent for controlled drug release. Journal of Pharmacy and Pharmacology 2017; 69 (2): 143-50. doi: 10.1111/jphp.12672
10. Al-Hashimi N, Babenko M, Saaed M, Kargar N, ElShaer A. The impact of natural and synthetic polymers in formulating micro and nanoparticles for anti-diabetic drugs. Current Drug Delivery 2021;18 (3): 271-88. doi: 10.2174/1567201817666200810111726
11. Chauhan P, Mahajan S, Prasad GB. Preparation and characterization of CS-ZnO-NC nanoparticles for imparting anti-diabetic activities in experimental diabetes. Journal of Drug Delivery Science and Technology 2019; 52: 738-47. doi: 10.2217/nnm.12.205
12. Li p, Dai Y, Zhang J, Wang A, Wei Q. Chitosan-alginate nanoparticles as a novel drug delivery system for nifedipine. International Journal of Biomedical Science 2008; 4 (3): 221–228. PMCID: PMC3614711 (www.ijbs.org Int J Biomed Sci vol. 4 no. 3 September 2008)
13. Katuwavila NP, Chandani Perera ADL, Samarakoon SR, Soysa P, Karunaratne V, Amaratunga GAJ et al. Chitosan-alginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells. Journal of Nanomaterials 2016; 12: 3178904. doi: 10.1155/2016/3178904
14. Azevedo MA, Bourbon AI, Vicente AA, Cerqueira MA. Alginate/chitosan nanoparticles for encapsulation and controlled release of vitamin B2. International Journal of Biological Macromolecules 2014; 71: 141-146. doi: 10.1016/j.ijbiomac.2014.05.036
15. Afshar M, Dini G, Vaezifar S, Mehdikhani M, Movahedi B. Preparation and characterization of sodium alginate/polyvinyl alcohol hydrogel containing drug-loaded chitosan nanoparticles as a drug delivery system. Journal of Drug Delivery Science and Technology 2020 Apr 1;56:101530. doi: 10.1016/j.jddst.2020.101530
16. Kaur P, Gondil VS, Chhibber S. A novel wound dressing consisting of PVA-SA hybrid hydrogel membrane for topical delivery of bacteriophages and antibiotics. International Journal of Pharmaceutics 2019; 572: 118779. doi: 10.1016/j.ijpharm.2019.118779
17. Chegeni M, Rozbahani ZS, Ghasemian M, Mehri M. Synthesis and application of the calcium alginate/SWCNT-Gl as a bio-nanocomposite for the curcumin delivery. International Journal of Biological Macromolecules 2020; 156: 504-13. doi: 10.1016/j.ijbiomac.2020.04.068
18. Nesamony J, Singh PR, Nada SE, Shah ZA, Kolling WM. Calcium alginate nanoparticles synthesized through a novel interfacial cross-linking method as a potential protein drug delivery system. Journal of pharmaceutical sciences 2012; 101 (6): 2177-84. doi: 10.1002/jps.23104
19. Zhang R, Lei L, Song Q, Li X. Calcium ion cross-linking alginate/dexamethasone sodium phosphate hybrid hydrogel for extended drug release. Colloids and Surfaces B: Biointerfaces 2019; 175: 569-75. doi: 10.1016/j.colsurfb.2018.11.083
20. Shafabakhsh R, Yousefi B, Asemi Z, Nikfar B, Mansournia MA et al. Chitosan: A compound for drug delivery system in gastric cancer-a review. Carbohydrate Polymers 2020; 242: 116403. doi: 10.1016/j.carbpol.2020.116403.
21. Nalinbenjapun S, Ovatlarnporn C. Chitosan-5-aminosalicylic acid conjugates for colon-specific drug delivery: Methods of preparation and in vitro evaluations. Journal of Drug Delivery Science and Technology 2020; 57: 101397. doi: 10.1016/j.jddst.2019.101397
22. Ren G, Clancy C, Tamer TM, Schaller B, Walker GM et al. Cinnamyl O-amine functionalized chitosan as a new excipient in direct compressed tablets with improved drug delivery. International Journal of Biological Macromolecules 2019; 141: 936-46. doi: 10.1016/j. ijbiomac.2019.08.265
23. Berger J, Reist M, Mayer JM, Felt O, Peppas NA et al. Structure and interactions in covalently and ionically crosslinked chitosan hydrogels for biomedical applications. European Journal of Pharmaceutics and Biopharmaceutics 2004; 57 (1): 19-34. doi: 10.1016/s0939- 6411(03)00161-9
24. Nalini T, Basha SK, Sadiq AM, Kumari VS, Kaviyarasu K. Development and characterization of alginate/chitosan nanoparticulate system for hydrophobic drug encapsulation. Journal of Drug Delivery Science and Technology 2019; 52: 65-72. doi: 10.1016/j.jddst.2019.04.002
25. Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. The Lancet 2019; 393 (10166): 31-9. doi: 10.1016/S0140-6736(18)32590-X
26. Rineh A, Mahmoodi N, Abdollahi M, Foroumadi A, Sorkhi M et al. Synthesis, analgesic and anti‐inflammatory activity of 4‐(2‐ phenoxyphenyl) semicarbazones. Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry 2007; 340 (8): 409-15. doi: 10.1002/ardp.200700045
27. Amirmahani N, Mahmoodi NO, Mohammadi Galangash M, Ghavidast A. Advances in nanomicelles for sustained drug delivery. Journal of Industrial and Engineering Chemistry 2017; 55 (1): 21-34. doi: 10.1016/j.jiec.2017.06.050
28. Mahmoodi NO, Ghavidast A, Amirmahani N. A comparative study on the nanoparticles for improved drug delivery systems. Journal of Photochemistry and Photobiology B: Biology 2016; 162: 681-693. doi: 10.1016/j.jphotobiol.2016.07.037
29. Peniche C, Howland I, Carrillo O, Zaldıvar C, Argüelles-Monal W. Formation and stability of shark liver oil loaded chitosan/calcium alginate capsules. Food Hydrocolloids 2004;18 (5): 865-71. doi: 10.1016/j.foodhyd.2004.02.001
30. Huang J, Peng T, Li Y, Zhan Z, Zeng Y et al. Ocular cubosome drug delivery system for timolol maleate: preparation, characterization, cytotoxicity, ex vivo, and in vivo evaluation. Aaps Pharmscitech 2017; 18 (8): 2919-26. doi: 10.1208/s12249-017-0763-8
31. Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine 2010; 6 (1): 153-60. doi: 10.1016/j.nano.2009.05.009
32. Nunthanid J, Puttipipatkhachorn S, Yamamoto K, Peck GE. Physical properties and molecular behavior of chitosan films. Drug Development and Industrial Pharmacy 2001; 27 (2): 143-57. doi: 10.1081/ddc-100000481
33. Hua S, Ma H, Li X, Yang H, Wang A. pH-sensitive sodium alginate/poly (vinyl alcohol) hydrogel beads prepared by combined Ca2+ crosslinking and freeze-thawing cycles for controlled release of diclofenac sodium. International Journal of Biological Macromolecules 2010; 46 (5): 517-23. doi: 10.1016/j.ijbiomac.2010.03.004
34. Soulairol I, Sanchez-Ballester NM, Aubert A, Tarlier N, Bataille B et al. Evaluation of the super disintegrant functionnalities of alginic acid and calcium alginate for the design of orodispersible mini tablets. Carbohydrate Polymers 2018; 197: 576-85. doi: 10.1016/j. carbpol.2018.06.002
35. Tripathi S, Mehrotra GK, Dutta PK. Physicochemical and bioactivity of cross-linked chitosan–PVA film for food packaging applications. International Journal of Biological Macromolecules 2009; 45 (4): 372-6. doi: 10.1016/j.ijbiomac.2009.07.006
36. Wu T, Li Y, Shen N, Yuan C, Hu Y. Preparation and characterization of calcium alginate-chitosan complexes loaded with lysozyme. Journal of Food Engineering 2018; 233: 109-16. doi: 10.1016/j.jfoodeng.2018.03.020
37. Basu SK, Rajendran A. Studies in the development of nateglinide loaded calcium alginate and chitosan coated calcium alginate beads. Chemical and Pharmaceutical Bulletin 2008; 56 (8): 1077-84. doi: 10.1248/cpb.56.1077