Sains Malaysiana 49(9)(2020): 2251-2260

http://dx.doi.org/10.17576/jsm-2020-4909-22

Synthesis and Characterization of Acylated Low Molecular Weight Chitosan and Acylated Low Molecular Weight Phthaloyl Chitosan

(Sintesis dan Pencirian Kitosan Berjisim Molekul Rendah Terasil dan Kitosan Ftaloil Berjisim Molekul Rendah Terasil)

RAHADIAN PERMADI, VICIT RIZAL EH SUK & MISNI MISRAN*

Department of Chemistry, Faculty of Science, Universiti Malaya, 50603 Kuala Lumpur, Federal Territory

Malaysia

Received: 15 October 2019/Accepted: 8 May 2020

ABSTRACT

Oral drug delivery is one of the most convenient routes due to its painless administration and high patient compliance. However, oral administration is becoming more difficult to be conducted due to its poor water solubility, poor dissolution rate, and low oral bioavailability in the gastrointestinal tract. Herein, we develop a strategy to produce a chemically modified chitosan using depolymerization and introducing hydrophobic groups onto the chitosan backbone through acylation. By modifying the structure of chitosan, we aim to overcome limitations of drug delivery before and after the oral administration. The successful acylation of protected (using phthalic anhydride) chitosan and unprotected (without phthalic anhydride) chitosan was proved by Fourier transform infrared (FTIR). FTIR was conducted not only to characterize the functional group changes but also to find quantization of degree of acylation (DA) and the degree of substitution (DS) of chitosan before and after acylation. The particle size of chitosan was found ranges from 300-500 nm with zeta potential value shifted from -50 mV to a more positive value as acid anhydrides concentration increased. The Field Emission Scanning Electron Microscopy (FESEM) images showed the low molecular weight of chitosan and acylated chitosan nanoparticle possess non-spherical form with hollow structure. In addition, the size obtained was in accordance with the size measured by particle size. Hydrophobically modified chitosan has been successfully synthesized via acylation on both primary hydroxyl and amine groups on the backbone of chitosan. This chemically modified chitosan can enhance drug solubilization as well as improving biocompatibility and degradability.

Keywords: Acylation; biomaterials; chitosan; oral drug delivery; polymer synthesis

ABSTRAK

Penghantaran ubatan melalui oral merupakan cara paling mudah berikutan tidak menyakitkan dan dipatuhi oleh pesakit. Walau bagaimanapun, kaedah oral menjadi susah untuk dijalankan berikutan keterlarutan air yang rendah, kadar pelarutan yang rendah dan bioketersediaan oral yang rendah pada saluran perut usus. Di sini, kami membangunkan strategi untuk menghasilkan kitosan terubah suai kimia menggunakan kaedah pempolimeran dan memperkenalkan kumpulan hidrofobik pada rantaian kitosan melalui tindakan pengasilan. Dengan mengubah suai struktur kitosan, kajian ini bertujuan untuk mengatasi batasan penghantaran ubatan sebelum dan selepas pengambilan secara oral. Kejayaan proses pengasilan pada kitosan terlindung (menggunakan anhidrida phthalik) dan kitosan tak terlindung (tanpa anhidrida phthalik) telah dibuktikan menggunakan spektroskopi inframerah transformasi Fourier (FTIR). FTIR bukan sahaja digunakan untuk pencirian kumpulan berfungsi tetapi juga untuk mengkuantumkan darjah pengasilan (DA) dan darjah penukargantian (DS) kitosan sebelum dan selepas pengasilan. Purata saiz zarah kitosan adalah antara 300-500 nm dengan nilai keupayaan zeta dianjakkan dari -50 mV ke nilai yang semakin positif selari dengan peningkatan kepekatan asid anhidrida. Mikrograf daripada mikroskop pengimbas elektron medan pancaran (FESEM) menunjukkan nanozarah kitosan berjisim molekul rendah dan kitosan terasil mempunyai bentuk tak sfera dengan struktur berongga. Tambahan lagi, saiz yang diperoleh adalah bertepatan dengan purata zarah saiz yang telah diukur. Kitosan terubah suai hidrofobik telah berjaya disintesis melalui pengasilan pada kumpulan hidroksil primer dan amina pada rantaian kitosan. Kitosan terubah suai kimia ini berupaya untuk meningkatkan pemelarutan ubatan dan juga menambahbaik biokeserasian dan penguraian.

Kata kunci: Biobahan; kitosan; pengasilan; penghantaran ubatan oral; sintesis polimer

REFERENCES

Araujo, F., das Neves, J., Martins, J.P., Granja, P.L., Santos, H.A. & Sarmento, B. 2017. Functionalized materials for multistage platforms in the oral delivery of biopharmaceuticals. Progress in Materials Science 89: 306-344.

Balata, G.F., Abdelhady, M.I.S., Mahmoud, G.M., Matar, M.A. & Abd El-Latif, A.N. 2018. Formulation of saudi propolis into biodegradable chitosan chips for vital pulpotomy. Current Drug Delivery 15(1): 97-109.

Banerjee, A., Qi, J.P., Gogoi, R., Wong, J. & Mitragotri, S. 2016. Role of nanoparticle size, shape and surface chemistry in oral drug delivery. Journal of Controlled Release 238: 176-185.

Bondar, O.V., Saifullina, D.V., Shakhmaeva, I.I., Mavlyutova, I.I. & Abdullin, T.I. 2012. Monitoring of the zeta potential of human cells upon reduction in their viability and interaction with polymers. Acta Naturae 4(1): 78-81.

Choi, H.J., Kim, M.C., Kang, S.M. & Montemagno, C.D. 2014. The osmotic stress response of split influenza vaccine particles in an acidic environment. Archives of Pharmacal Research 37(12): 1607-1616.

Choi, H.J., Ebersbacher, C.F., Kim, M.C., Kang, S.M. & Montemagno, C.D. 2013. A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment. PloS ONE 8(6): e66316.

Ensign, L.M., Cone, R. & Hanes, J. 2012. Oral drug delivery with polymeric nanoparticles: The gastrointestinal mucus barriers. Advanced Drug Delivery Reviews 64(6): 557-570.

He, Y., Miao, J., Chen, S., Zhang, R., Zhang, L., Tang, H. & Yang, H. 2019. Preparation and characterization of a novel positively charged composite hollow fiber nanofiltration membrane based on chitosan lactate. RSC Advances 9(8): 4361-4369.

Homayun, B., Lin, X.T. & Choi, H.J. 2019. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics 11(3): 129.

Hu, Q.B. & Luo, Y.C. 2018. Recent advances of polysaccharide-based nanoparticles for oral insulin delivery. International Journal of Biological Macromolecules 120(Part A): 775-782.

Kasaai, M.R. 2008. A review of several reported procedures to determine the degree of N-acetylation for chitin and chitosan using infrared spectroscopy. Carbohydrate Polymers 71(4): 497-508.

Khajuria, D.K., Patil, O.N., Karasik, D. & Razdan, R. 2018. Development and evaluation of novel biodegradable chitosan based metformin intrapocket dental film for the management of periodontitis and alveolar bone loss in a rat model. Archives of Oral Biology 85: 120-129.

Klodzinska, E., Szumski, M., Dziubakiewicz, E., Hrynkiewicz, K., Skwarek, E., Janusz, W. & Buszewski, B. 2010. Effect of zeta potential value on bacterial behavior during electrophoretic separation. Electrophoresis 31(9): 1590-1596.

Kurita, K., Ikeda, H., Yoshida, Y., Shimojoh, M. & Harata, M. 2002. Chemoselective protection of the amino groups of chitosan by controlled phthaloylation: Facile preparation of a precursor useful for chemical modifications. Biomacromolecules 3(1): 1-4.

Lee, D., Quan, Z.S., Lu, C., Jeong, J.A., Song, C., Song, M.S. & Chai, K.Y. 2012. Preparation and physical properties of chitosan benzoic acid derivatives using a phosphoryl mixed anhydride system. Molecules 17(2): 2231-2239.

Lee, K.Y., Jo, W.H., Kwon, I.C., Kim, Y.H. & Jeong, S.Y. 1998. Structural determination and interior polarity of self-aggregates prepared from deoxycholic acid-modified chitosan in water. Macromolecules 31(2): 378-383.

Mai, T.T.T., Ha, P.T., Pham, H.N., Le, T.T.H., Pham, H.L., Phan, T.B.H. & Nguyen, X.P. 2012. Chitosan and O-carboxymethyl chitosan modified Fe₃O₄ for hyperthermic treatment. Advances in Natural Sciences: Nanoscience and Nanotechnology 3(1): 015006.

Mekhail, G.M., Kamel, A.O., Awad, G.A.S. & Mortada, N.D. 2012. Anticancer effect of atorvastatin nanostructured polymeric micelles based on stearyl-grafted chitosan. International Journal of Biological Macromolecules 51(4): 351-363.

Priyadarshini, N, Sampath, M., Kumar, S. & Kamachi Mudali, U. 2013. Particle size variation and prediction of molecular weight of Bi (III) dydrolyzed polymer using light scattering technique. ISRN Inorganic Chemistry 2013: Article ID. 194120.

Ren, X., Chen, C., Hou, Y., Huang, M., Li, Y.B., Wang, D.Q. & Zhang, L. 2018. Biodegradable chitosan-based composites with dual functions acting as the bone scaffold and the inflammation inhibitor in the treatment of bone defects. International Journal of Polymeric Materials and Polymeric Biomaterials 67(12): 703-710.

Takayama, K., Hirata, M., Machida, Y., Masada, T., Sannan, T. & Nagai, T. 1990. Effect of interpolymer complex-formation on bioadhesive property and drug release phenomenon of compressed tablet consisting of chitosan and sodium hyaluronate. Chemical & Pharmaceutical Bulletin 38(7): 1993-1997.

Tan, H.W. & Misran, M. 2013. Polysaccharide-anchored fatty acid liposome. International Journal of Pharmaceutics 441(1-2): 414-423.

Tiew, S.X. & Misran, M. 2017. Encapsulation of salicylic acid in acylated low molecular weight chitosan for sustained release topical application. Journal of Applied Polymer Science 134(36): 44849.

Werle, M., Takeuchi, H. & Bernkop-Schnurch, A. 2009. Modified chitosans for oral drug delivery. Journal of Pharmaceutical Sciences 98(5): 1643-1656.

Wu, C., Zhou, S.Q. & Wang, W. 1995. A dynamic laser light-scattering study of chitosan in aqueous-solution. Biopolymers 35(4): 385-392.

Yu, Z., Li, B.Q., Chu, J.Y. & Zhang, P.F. 2018. Silica in situ enhanced PVA/chitosan biodegradable films for food packages. Carbohydrate Polymers 184(2018): 214-220.

Yuan, Y. & Lee, T.R. 2013. Surface science techniques. Springer Series in Surface Sciences 51(1): 3-34.

*Corresponding author; email: misni@um.edu.my