Synthesis of thiolated nanochitosan as a carrier of biperidine using two cross linkers Tripolyphosphate (TPP) and Genipine and evaluation of their release and toxicity

Amini Toolarood Payin, Fakhimeh; Salarian, Reza; Hosseini, Seyed Mehdi; Shahavi, Mohammad Hasan; Ebadi, Tahmine

Synthesis of thiolated nanochitosan as a carrier of biperidine using two cross linkers Tripolyphosphate (TPP) and Genipine and evaluation of their release and toxicity

Document Type : Original Research

Authors

Fakhimeh Amini Toolarood Payin ¹

Reza Salarian ²

seyed mehdi hosseini ³

Mohammad Hasan Shahavi ⁴

tahmine ebadi ⁵

¹ graduated master's degree in biomedical engineering from Maziar University, Royan, IRAN

² department of biomedical engineering, Maziar University, Royan, IRAN

³ department of medicinal plants, Amol University of Special Modern Technologies, Amol, IRAN

⁴ Assistant professor,Faculty of Modern Technologies Engineering, Amol University of Special Modern Technologies, Amol, Iran

⁵ faculty of chemical engineering, babol noshirvani university of technology, Babol, P.O. Box 47148-73113

Abstract

Background: Modern science in drug delivery systems has long been paid to effectively design drug delivery systems, to reduce side effects, increasing bioavailability, targeted drug delivery, and passing through blood-brain barriers. Nanoparticles are very important as carriers because they carry different types of drugs to different parts of the body at the right time. Method: In the present study, thiolated nano chitosan loaded with Biperiden was synthesized by ion gel method using two types of crosslinkers (tripolyphosphate and genipin) and their efficiency was investigated. Results: FTIR analysis confirmed the successful synthesis of various stages of thiolated nano chitosan loaded with Biperiden by both crosslinkers. SEM images showed that as-synthesized nano-carriers have a nanorod structure and nanocarriers crosslinked by genipin had a more regular structure with a size of about 150 nm than nanocarrier crosslinked by TPP with a size of approximately 200 nm. In vitro drug release and cytotoxicity studies showed nano-carriers crosslinked by genipin have had a higher release and less cytotoxicity than nano-carriers crosslinked by TPP. Conclusion: Considering the lower toxicity and delayed release of nanoparticles synthesized with genipine than nanocarriers synthesized with TPP, the use of this nanocarrier increases the bioavailability of the drug and can be used as a suitable drug delivery system.

Keywords

Chitosan nanoparticles

ion gel method

Biperiden

Tripolyphosphate

Genipin

20.1001.1.23222115.1401.13.3.6.3

Subjects

Nanotechnology

1. Mehta, P., Dry powder inhalers: a focus on advancements in novel drug delivery systems. Journal of drug delivery, 2016. 2016.
2. Mincea, M., A. Negrulescu, and V. Ostafe, Preparation, modification, and applications of chitin nanowhiskers: a review. Rev. Adv. Mater. Sci, 2012. 30(3): p. 225-242.
3. Kaparissides, C., et al., Recent advances in novel drug delivery systems. Journal of Nanotechnology online, 2006. 2: p. 1-11.
4. Xiao, Y., et al., Sorafenib and gadolinium co-loaded liposomes for drug delivery and MRI-guided HCC treatment. Colloids and Surfaces B: Biointerfaces, 2016. 141: p. 83-92.
5. Hasan, A.S., et al., Reduction of the in vivo burst release of insulin-loaded microparticles. Journal of Drug Delivery Science and Technology, 2015. 30: p. 486-493.
6. Petkar, K.C., et al., Nanostructured materials in drug and gene delivery: a review of the state of the art. Critical Reviews™ in Therapeutic Drug Carrier Systems, 2011. 28(2).
7. Singh, R. and J.W. Lillard Jr, Nanoparticle-based targeted drug delivery. Experimental and molecular pathology, 2009. 86(3): p. 215-223.
8. Kamaly, N., et al., Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chemical reviews, 2016. 116(4): p. 2602-2663.
9. Luo, Y. and Q. Wang, Recent development of chitosan-based polyelectrolyte complexes with natural polysaccharides for drug delivery. International journal of biological macromolecules, 2014. 64: p. 353-367.
10. Abd Elgadir, M., et al., Impact of chitosan composites and chitosan nanoparticle composites on various drug delivery systems: A review. Journal of food and drug analysis, 2015. 23(4): p. 619-629.
11. Naskar, S., K. Kuotsu, and S. Sharma, Chitosan-based nanoparticles as drug delivery systems: a review on two decades of research. Journal of drug targeting, 2019. 27(4): p. 379-393.
12. Fonseca-Santos, B. and M. Chorilli, An overview of carboxymethyl derivatives of chitosan: Their use as biomaterials and drug delivery systems. Materials Science and Engineering: C, 2017. 77: p. 1349-1362.
13. Fernández-Urrusuno, R., et al., Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharmaceutical research, 1999. 16(10): p. 1576-1581.
14. Rostami, E., Progresses in targeted drug delivery systems using chitosan nanoparticles in cancer therapy: A mini-review. Journal of Drug Delivery Science and Technology, 2020. 58: p. 101813.
15. Wassmer, S., et al., Chitosan microparticles for delivery of proteins to the retina. Acta biomaterialia, 2013. 9(8): p. 7855-7864.
16. Sadeghi, M., F. Ganji, and S.M. Taghizadeh, Preparation and Optimization of Labeled Chitosan Nanoparticles and Evaluation of their Release from Transdermal Drug Delivery System. IRANIAN JOURNAL OF POLYMER SCIENCE AND TECHNOLOGY (PERSIAN),[online], 2015. 28(4): p. 333-344.
17. Kumar, S., et al., Preparation and characterization of indomethacin loaded ionically crosslinked microspheres using chitosan. Der Pharmacia Lett., 2012. 4: p. 33-41.
18. Tripathy, S., et al., Synthesis, characterization of chitosan–tripolyphosphate conjugated chloroquine nanoparticle and its in vivo anti-malarial efficacy against rodent parasite: A dose and duration dependent approach. International journal of pharmaceutics, 2012. 434(1-2): p. 292-305.
19. Goyal, S. and S. Arora, IN-SITU NASAL GEL OF LEVODOPA FOR BRAIN TARGETING USING CHITOSAN–THIOGLYCOLIC ACID CONJUGATE AND MUSK KETONE BY EFFLUX TRANSPORT MODULATION. 2015.
20. Md, S., et al., Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. European Journal of Pharmaceutical Sciences, 2013. 48(3): p. 393-405.
21. Garbayo, E., E. Ansorena, and M.J. Blanco-Prieto, Drug development in Parkinson's disease: from emerging molecules to innovative drug delivery systems. Maturitas, 2013. 76(3): p. 272-278.
22. Sharma, S., S. Lohan, and R. Murthy, Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery. Drug development and industrial pharmacy, 2014. 40(7): p. 869-878.
23. Domaratzki, R.E. and A. Ghanem, Encapsulation and release of cladribine from chitosan nanoparticles. Journal of applied polymer science, 2013. 128(3): p. 2173-2179.
24. Omer, A.M., et al., Formulation of quaternized aminated chitosan nanoparticles for efficient encapsulation and slow release of curcumin. Molecules, 2021. 26(2): p. 449.
25. Mi, F.L., et al., In vitro evaluation of a chitosan membrane cross-linked with genipin. J Biomater Sci Polym Ed, 2001. 12(8): p. 835-50.
26. Nasrabadi, M., A. Morsali, and S.A. Beyramabadi, An applied quantum-chemical model for genipin-crosslinked chitosan (GCS) nanocarrier. International Journal of Biological Macromolecules, 2020. 165: p. 1229-1240.
27. Ubaid, M. and G. Murtaza, Fabrication and characterization of genipin cross-linked chitosan/gelatin hydrogel for pH-sensitive, oral delivery of metformin with an application of response surface methodology. International journal of biological macromolecules, 2018. 114: p. 1174-1185.
28. Khatun, B., et al., Genipin crosslinked curcumin loaded chitosan/montmorillonite K-10 (MMT) nanoparticles for controlled drug delivery applications. Journal of microencapsulation, 2018. 35(5): p. 439-453.
29. Muzzarelli, R.A., et al., Genipin-crosslinked chitosan gels and scaffolds for tissue engineering and regeneration of cartilage and bone. Marine drugs, 2015. 13(12): p. 7314-7338.
30. Shahnaz, G., et al., Thiolated chitosan nanoparticles for the nasal administration of leuprolide: bioavailability and pharmacokinetic characterization. International journal of pharmaceutics, 2012. 428(1-2): p. 164-170.
31. Anitha, A., et al., Development of mucoadhesive thiolated chitosan nanoparticles for biomedical applications. Carbohydrate Polymers, 2011. 83(1): p. 66-73.
32. Li, Y.-H., et al., Characterization of the modified chitosan membrane cross-linked with genipin for the cultured corneal epithelial cells. Colloids and Surfaces B: Biointerfaces, 2015. 126: p. 237-244.
33. Zhang, Y., Y. Yang, and T. Guo, Genipin-crosslinked hydrophobical chitosan microspheres and their interactions with bovine serum albumin. Carbohydrate polymers, 2011. 83(4): p. 2016-2021.
34. Barahuie, F., et al., Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system. International journal of nanomedicine, 2017. 12: p. 2361.
35. Kamiloglu, S., et al., Guidelines for cell viability assays. Food Frontiers, 2020. 1(3): p. 332-349.
36. Kapuscinski, J., DAPI: a DNA-specific fluorescent probe. Biotechnic & Histochemistry, 1995. 70(5): p. 220-233.
37. Sankararamakrishnan, N., et al., Removal of hexavalent chromium using a novel cross linked xanthated chitosan. Bioresource Technology, 2006. 97(18): p. 2377-2382.
38. Gupta, A., S.R. Vidyarthi, and N. Sankararamakrishnan, Studies on glutaraldehyde crosslinked xanthated chitosan towards the removal of mercury (II) from contaminated water streams. Environmental Engineering & Management Journal (EEMJ), 2015. 14(5).
39. Peng, X., et al., Effective biosorption of patulin from apple juice by cross-linked xanthated chitosan resin. Food Control, 2016. 63: p. 140-146.
40. Chen, A., et al., Carbon disulfide-modified magnetic ion-imprinted chitosan-Fe (III): a novel adsorbent for simultaneous removal of tetracycline and cadmium. Carbohydrate polymers, 2017. 155: p. 19-27.
41. Bagheri, M., et al., Application of chitosan-citric acid nanoparticles for removal of chromium (VI). International journal of biological macromolecules, 2015. 80: p. 431-444.
42. Csaba, N., M. Köping-Höggård, and M.J. Alonso, Ionically crosslinked chitosan/tripolyphosphate nanoparticles for oligonucleotide and plasmid DNA delivery. Int J Pharm, 2009. 382(1-2): p. 205-14.
43. Ta, Q., et al., Chitosan nanoparticles for enhancing drugs and cosmetic components penetration through the skin. European Journal of Pharmaceutical Sciences, 2021. 160: p. 105765.
44. Sadigh-Eteghad, S., et al., Effects of Levodopa loaded chitosan nanoparticles on cell viability and caspase-3 expression in PC12 neural like cells. Neurosciences Journal, 2013. 18(3): p. 281-283.