Preparation and In Vitro Characterization of Carbamazepine-Loaded Chitosan-Coated/Uncoated PLGA and Zein Nanoparticles

Abstract

The aim of this study is to prepare CBZ-loaded chitosan (Ch)- coated/uncoated poly(lactic-co-glycolic acid) (PLGA) and Zein (using 20 mg or 40 mg Zein) nanoparticles (CBZ-PLGA-Zein-NPs or CBZ-PLGA-Zein-Ch-NPs) and to characterize (Particle size, PDI, zeta potential, percent encapsulation efficiency (EE%), FT-IR, DSC and XRD analyzes, and in vitro release study) them in vitro. These nanoparticles were prepared using a modified emulsification-solvent evaporation method. The particle sizes of CBZ-PLGA-Zein(20)-NPs, CBZ-PLGA-Zein(40)-NPs and CBZ-PLGA-Zein(20)-Ch-NPs were found to be about 222 nm, 245 nm and 221 nm, respectively. The PDI value of all NP formulations was below 0.3. This indicates a narrow particle size distribution. The EE% values of CBZ-PLGA-Zein(20)-NPs, CBZ-PLGA-Zein(40)-NPs and CBZ-PLGA-Zein(20)-Ch-NPs were determined as about 64%, 56% and 62%, respectively. The coating of the optimum formulation (containing 20 mg Zein) with chitosan did not lead to a significant difference in the particle size and EE% value of this formulation (P>0.05). A sustained release of CBZ from all prepared NPs formulations was achieved until 48th h. In conclusion, CBZ-PLGA-Zein(20 mg or 40 mg)-NPs and CBZ-PLGA-Zein(20 mg)-Ch-NPs were successfully prepared and characterized in vitro.

Keywords

• Epilepsy
• Chitosan
• Nanoparticles
• PLGA
• Zein

References

1. André de Almeida Campos L, Francisco Silva Neto A, Cecília Souza Noronha M, Ferreira de Lima M, Macário Ferro Cavalcanti I, Stela Santos-Magalhães N. 2023. Zein nanoparticles for drug delivery: Preparation methods and biological applications. Int J Pharm, 635: 122754. https://doi.org/10.1016/j.ijpharm.2023.122754
2. Caliandro R, Di Profio G, Nicolotti O. 2013. Multivariate analysis of quaternary carbamazepine-saccharin mixtures by X-ray diffraction and infrared spectroscopy. J Pharm Biomed Anal, 78-79: 269-279. https://doi.org/10.1016/j.jpba.2013.01.042
3. Clogston JD, Patri AK. Zeta potential measurement. 2011. Methods Mol Biol, 697: 63-70. https://doi.org/10.1007/978-1-60327-198-1_6
4. Dandamudi M, McLoughlin P, Behl G, Rani S, Coffey L, Chauhan A. 2021. Chitosan-coated PLGA nanoparticles encapsulating triamcinolone acetonide as a potential candidate for sustained ocular drug delivery. Pharmaceutics, 13(10): 1590. https://doi.org/10.3390/pharmaceutics13101590
5. Devinsky O, Vezzani A, O’Brien TJ, Jette N, Scheffer IE, de Curtis M. 2018. Epilepsy. Nat Rev Dis Primers, 4(1): 1-24. https://doi.org/10.1038/nrdp.2018.24
6. Gagliardi A, Paolino D, Costa N, Fresta M, Cosco D. 2021. Zein- vs PLGA-based nanoparticles containing rutin: A comparative investigation. Mater Sci Eng C Mater Biol Appl, 118: 111538. https://doi.org/10.1016/j.msec.2020.111538
7. Green SF, Nguyen P, Kaalund-Hansen K, Rajakulendran S, Murphy E. 2020. Effectiveness, retention, and safety of modified ketogenic diet in adults with epilepsy at a tertiary-care centre in the UK. J Neurol, 267(4): 1171-1178. https://doi.org/10.1007/s00415-019-09658-6
8. Guery D, Rheims S. 2021. Clinical management of drug resistant epilepsy: A review on current strategies. Neuropsychiatr Dis Treat, 17: 2229-2242. https://doi.org/10.2147/NDT.S256699

9. Kandilli B, Uğur AB, Çetin M, Miloğlu FD. 2018. A simple HPLC-UV method for simultaneous determination of levetiracetam and carbamazepine. HUJPHARM, 38(2): 58-64.
10. Kandilli B, Ugur Kaplan AB, Cetin M, Taspinar N, Ertugrul MS, Aydin IC, et al. 2020 Carbamazepine and levetiracetam-loaded PLGA nanoparticles prepared by nanoprecipitation method: in vitro and in vivo studies. Drug Dev Ind Pharm, 46(7): 1063-1072. https://doi.org/10.1080/03639045.2020.1769127
11. Kanner AM, Bicchi MM. 2022. Antiseizure medications for adults with epilepsy: A review. JAMA, 327(13): 1269-1281. https://doi.org/10.1001/jama.2022.3880
12. Krstić M, Popović M, Dobričić V, Ibrić S. 2015. Influence of solid drug delivery system formulation on poorly water-soluble drug dissolution and permeability. Molecules, 20(8): 14684-98. https://doi.org/10.3390/molecules200814684
13. Liu E, Su Z, Yang C, Ji Y, Liu B, Meng X. 2021. Fabrication, characterization and properties of DHA-loaded nanoparticles based on zein and PLGA. Food Chem, 360: 129957. https://doi.org/10.1016/j.foodchem.2021.129957
14. Lo JCY. 2014. Carbamazepine. In: Wexler P, editor. Encyclopedia of Toxicology (Third Edition). Academic Press, Oxford, UK, pp: 665-667.
15. Ma X, Müller F, Huang S, Lowinger M, Liu X, Schooler R, et al. 2020. Influence of carbamazepine dihydrate on the preparation of amorphous solid dispersions by hot melt extrusion. Pharmaceutics, 12(4): 379. https://doi.org/10.3390/pharmaceutics12040379
16. Maan JS, Duong T vi H, Saadabadi A. Carbamazepine. 2024. URL: http: //www.ncbi.nlm.nih.gov/books/NBK482455/ (accessed 26 February 2024).
17. Manole AM, Sirbu CA, Mititelu MR, Vasiliu O, Lorusso L, Sirbu OM. 2023. State of the art and challenges in epilepsy—A narrative review. J Pers Med, 13(4): 623. https://doi.org/ 10.3390/jpm13040623
18. Mura S, Hillaireau H, Nicolas J, Le Droumaguet B, Gueutin C, Zanna S. 2011. Influence of surface charge on the potential toxicity of PLGA nanoparticles towards Calu-3 cells. Int J Nanomedicine, 6: 2591-2605. https://doi.org/10.2147/IJN.S24552
19. Pascoli M, de Lima R, Fraceto LF. 2018. Zein nanoparticles and strategies to improve colloidal stability: A mini-review. Front Chem, 6: 6. https://doi.org/10.3389/fchem.2018.00006
20. Pauluk D, Padilha AK, Khalil NM, Mainardes RM. 2019. Chitosan-coated zein nanoparticles for oral delivery of resveratrol: Formation, characterization, stability, mucoadhesive properties and antioxidant activity. Food Hydrocolloids, 94: 411-417. https://doi.org/10.1016/j.foodhyd.2019.03.042
21. Pearce RE, Lu W, Wang Y, Uetrecht JP, Correia MA, Leeder JS. 2008. Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine. Drug Metab Dispos, 36(8): 1637-1649. https://doi.org/10.1124/dmd.107.019562
22. Pinto MAL, Ambrozini B, Ferreira APG, Cavalheiro ÉTG. 2014. Thermoanalytical studies of carbamazepine: hydration/dehydration, thermal decomposition, and solid phase transitions. Braz J Pharm Sci, 50(4): 877-884.
23. Qushawy M, Prabahar K, Abd-Alhaseeb M, Swidan S, Nasr A. 2019. Preparation and evaluation of carbamazepine solid lipid nanoparticle for alleviating seizure activity in pentylenetetrazole-kindled mice. Molecules, 24(21): 3971. https://doi.org/10.3390/molecules24213971
24. Sakhi M, Khan A, Iqbal Z, Khan I, Raza A, Ullah A. 2022. Design and characterization of paclitaxel-loaded polymeric nanoparticles decorated with trastuzumab for the effective treatment of breast cancer. Front Pharmacol, 13: 855294. https://doi.org/10.3389/fphar.2022.855294”
25. Sarmast ST, Abdullahi AM, Jahan N. 2020. Current classification of seizures and epilepsies: Scope, limitations and recommendations for future action. Cureus, 12(9): e10549. https://doi.org/10.7759/cureus.10549.
26. Scioli Montoto S, Sbaraglini ML, Talevi A, Couyoupetrou M, Di Ianni M, Pesce GO. 2018. Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation. Colloids Surf B Biointerfaces, 167: 73-81. https://doi.org/10.1016/j.colsurfb.2018.03.052
27. Stafstrom CE, Carmant L. 2015. Seizures and epilepsy: An overview for neuroscientists. Cold Spring Harb Perspect Med, 5(6): a022426. https://doi.org/10.1101/cshperspect.a022426
28. Swider E, Koshkina O, Tel J, Cruz LJ, de Vries IJM, Srinivas M. 2018. Customizing poly(lactic-co-glycolic acid) particles for biomedical applications. Acta Biomater, 73: 38-51. https://doi.org/10.1016/j.actbio.2018.04.006
29. Ugur Kaplan AB, Cetin M, Bayram C, Yildirim S, Taghizadehghalehjoughi A, Hacimuftuoglu A. 2023. In vivo evaluation of nanoemulsion formulations for metformin and repaglinide alone and combination. J Pharm Sci, 112(5): 1411-1426. https://doi.org/10.1016/j.xphs.2023.01.008
30. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R. 2019. Ketogenic Diet and Epilepsy. Nutrients, 11(10): 2510. https://doi.org/10.3390/nu11102510
31. Uzunović A, Vranić E, Hadzidedić S. 2010. Impairment of the in vitro release of carbamazepine from tablets. Bosn J Basic Med Sci, 10(3): 234-238. https://doi.org/10.17305/bjbms.2010.2693
32. Valo H, Peltonen L, Vehviläinen S, Karjalainen M, Kostiainen R, Laaksonen T. 2009. Electrospray encapsulation of hydrophilic and hydrophobic drugs in poly(l-lactic acid) nanoparticles. Small, 5(15): 1791-1798. https://doi.org/10.1002/smll.200801907
33. Wang Z, Chen B, Quan G, Li F, Wu Q, Dian L. 2012. Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica. Int J Nanomedicine, 7: 5807-5818. https://doi.org/10.2147/IJN.S37650
34. WHO. 2024. Epilepsy. URL: https://www.who.int/news-room/fact-sheets/detail/epilepsy (accessed 26 February 2024).
35. Wu D, Fei F, Zhang Q, Wang X, Gong Y, Chen X. 2022. Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy. Sci Adv, 8(2): eabm3381. https://doi.org/10.1126/sciadv.abm3381
36. Zybina A, Anshakova A, Malinovskaya J, Melnikov P, Baklaushev V, Chekhonin V. 2018. Nanoparticle-based delivery of carbamazepine: A promising approach for the treatment of refractory epilepsy. Int J Pharm, 547(1): 10-23. https://doi.org/10.1016/j.ijpharm.2018.05.023