Sains Malaysiana 49(9)(2020): 2269-2279

http://dx.doi.org/10.17576/jsm-2020-4909-24

Improving Rate of Gelatin/Carboxymethylcellulose Dissolving Microneedle for Transdermal Drug Delivery

(Penambah Baik Kadar Larutan Jarum Mikro Gelatin/Karboksimetilselulosa untuk Penghantaran Ubat Transdermal)

NUR AFIQAH MUSTAFA KAMAL¹, TUAN MAZLELAA TUAN MAHMOOD³, ISHAK AHMAD^1,2 & SURIA RAMLI^1,2*

¹Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

²Polymer Research Center (PORCE), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia

³Drug and Herbal Development Centres, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Sultan Abdul Aziz, 50300 Kuala Lumpur, Federal Territory, Malaysia

Diserahkan: 15 Oktober 2019/Diterima: 8 Mei 2020

ABSTRACT

Gelatin has been widely used as a nature-derived biopolymer material due to its high biocompatibility and abundance. However, multiple fabrication steps for the moulding process may limit its application to microneedle technology as biomedical application. This research focused on physical, chemical, and mechanical characteristics of gelatin-based dissolving microneedle (DMN) by adding in various concentrations of carboxymethylcellulose. Carboxymethylcellulose (CMC) derived from kenaf bast fibre were extracted by alkaline treatment and esterification process, followed by fabrication of DMN with gelatin using centrifuge-casting method. The formulation of G/CMC6 demonstrated the highest mechanical strength of 11.2 N by texture analyzer; hence, G/CMC6 was chosen for further investigate of its intra- and intermolecular bond, amorphous study, and its geometry by Fourier Transform Infrared (FTIR), X-ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). FTIR showed various chemical interactions involved including hydrogen bonding, dipole-dipole and charge effect. The XRD result shows amorphous peak of gelatin decreased at 2θ = 20 - 21° with the addition of CMC. The height of microneedle arrays also decreased from its micromould by 36.7% due to agglomeration of CMC. Considering the biodegradability and the improvement of gelatin-based DMN mechanical properties by carboxymethylcellulose, the combination of gelatin and CMC is one of great potential for delivering drugs using microneedle.

Keywords: CMC; dissolving microneedle; gelatin; mechanical characteristics

ABSTRAK

Gelatin digunakan secara meluas sebagai sumber terbitan biopolimer semula jadi kerana sifatnya yang tinggi biokeserasian. Walau bagaimanapun, kaedah fabrikasi berganda bagi proses acuan dalam aplikasi teknologi jarum mikro adalah terhad. Kajian ini memfokus kepada sifat kimia, fizikal dan mekanikal jarum mikro terlarut (DMN) berasaskan gelatin dengan penambahan pelbagai variasi kepekatan selulosa karboksimetil (CMC). CMC yang digunakan merupakan terbitan daripada serabut kenaf yang diekstrak oleh rawatan alkali dan proses esterifikasi, kemudiannya gelatin dan variasi kepekatan CMC digunakan untuk memfabrikasikan jarum mikro terlarut dengan menggunakan kaedah tuangan-emparan. Formulasi G/CMC6 telah menunjukkan kekuatan mekanikal jarum mikro tertinggi dengan 11.2 N oleh analisis tekstur. Oleh itu, G/CMC6 dipilih untuk mengkaji ikatan intra- dan intermolekul, amorfus dan geometri menggunakan instrumentasi analisis spektroskopi transformasi Fourier infra merah (FTIR), pembelauan X-ray (XRD) dan mikroskopi imbasan elektron (SEM). FTIR menunjukkan terdapat interaksi kimia berlaku yang melibatkan ikatan hidrogen, dwikutub dan kesan cas. Keputusan XRD pula menunjukkan puncak amorfus gelatin semakin menurun pada 2θ = 20 - 21° dengan penambahan CMC. Panjang jarum mikro pula berkurangan semasa proses pengeringan, iaitu berkurangan sebanyak 36.7% daripada acuan atas faktor aglomerasi oleh CMC. Kajian ini telah membuktikan bahawa biodegradasi dan peningkatan mekanikal jarum mikro berasaskan gelatin dan CMC salah satu potensi untuk menghantar ubat dalam bidang farmaseutis.

Kata kunci: CMC; gelatin; jarum mikro; terlarut; sifat mekanikal

RUJUKAN

Ali, N.H., Amin, M.C.I.M. & Ng, S.F. 2019. Sodium carboxymethyl cellulose hydrogels containing reduced graphene oxide (rGO) as a functional antibiofilm wound dressing. Journal of Biomaterials Science, Polymer Edition 30(8): 629-645.

Atef, M., Rezaei, M. & Behrooz, R. 2014. Preparation and characterization agar-based nanocomposite film reinforced by nanocrystalline cellulose. International Journal of Biological Macromolecules 70: 537-544.

Barry, B. 2001. Novel mechanisms and devices to enable successful transdermal drug delivery. European Journal of Pharmaceutical Sciences 14: 101-114.

Bono, A., Ying, P.H., Yan, F.Y., Muei, C.L., Sarbatly, R. & Krishnaiah, D. 2009. Synthesis and characterization of carboxymethyl cellulose from palm kernel cake. Advance Nature Apploed Sciecnce 3(1): 5-11.

Chai, M.N. & Isa, M.I.N. 2013. The oleic acid composition effect on the carboxymethyl cellulose based biopolymer electrolyte. Journal Crystallization Process Technology 3: 1-4.

Chen, M.C., Ling, M.H., Lai, K.Y. & Pramudityo, E. 2012. Chitosan microneedle patches for sustained transdermal delivery of macromolecules. Biomacromolecules 13(12): 4022-4031.

Dangol, M., Yang, H., Li, C.G., Lahiji, S.F., Kim, S., Ma, Y. & Jung, H. 2016. Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via DMNs. Journal of Controlled Release 223: 118-125.

Esteghlal, S., Niakousari, M. & Hosseini, S.M.H. 2018. Physical and mechanical properties of gelatin-CMC composite films under the influence of electrostatic interactions. International Journal of Biological Macromolecules 114: 1-9.

Hosseini, S.F., Rezaei, M., Zandi, M. & Ghavi, F.F. 2013. Preparation and functional properties of fish gelatin-chitosan blend edible films. Food Chemistry 136(3-4): 1490-1495.

Hu, D., Wang, H. & Wang, L. 2016. Physical properties and antibacterial activity of quaternized chitosan/carboxymethyl cellulose blend films. LWT- Food Science and Technology 65: 398-405.

Hube, M.A., Ferrer, A., Tyagi, P., Yin, Y., Salas, C., Pal, L. & Rojas, O.J. 2017. Nanocellulose in thin films, coatings, and plies for packaging applications: A review. BioResources12(1): 2143-2233.

Ishak, M.R., Leman, Z., Sapuan, S.M., Edeerozey, A.M.M. & Othman, I.S. 2010. Mechanical properties of kenaf bast and core fibre reinforced unsaturated polyester composites. IOP Conference Series: Material Science Engineering 11: 012006.

Ito, Y., Hirono, M., Fukushima, K., Sugioka, N. & Takada, K. 2012. Two-layered DMNs formulated with intermediate-acting insulin. International Journal of Pharmaceutics 436(1-2): 387-393.

Hazirah, M.N., Isa, M.I.N. & Sarbon, N.M. 2016. Effect of xanthan gum on the physical and mechanical properties of gelatin-carboxymethyl cellulose film blends. Food Packaging and Shelf Life 9: 55-63.

Jafirin, S., Ahmad, I. & Ahmad, A. 2014. Carboxymethyl cellulose from kenaf reinforced composite polymer electrolytes based 49% poly(methyl methacrylate)-grafted natural rubber. Malaysian Journal of Analytical Sciences 18(2): 376-384.

Jahit, I.S., Nazmi, N.N.M., Isa, M.I.N. & Sarbon, N.M. 2016. Preparation and physical properties of gelatin/CMC/chitosan composite films as affected by drying temperature. International Food Research Journal 23(3): 1068-1074.

Kamath, M.G., Bhat, G.S., Parikh, D.V. & Mueller, D. 2005. Cotton fiber nonwovens for automotive composites. International Nonwovens Journal. doi/10.1177/1558925005os-1400105.

Kumsah, C.A., Pass, G. & Phillips, G.O. 1976. The interaction between sodium carboxymethylcellulose and water. Journal of Solution Chemistry 5(11): 799-806.

Lai, J.Y. 2010. Biocompatibility of chemically cross-linked gelatin hydrogels for ophthalmic use. Journal of Material Science: Materials in Medicine 21(6): 1899-1911.

Lan, W., He, L. & Liu, Y. 2018. Preparation and properties of sodium carboxymethyl cellulose/sodium alginate/chitosan composite film. Coatings 8(8): 291.

Marques, N.D.N., Balaban, R.D.C., Halila, S. & Borsali, R. 2018. Synthesis and characterization of carboxymethylcellulose grafted with thermoresponsive side chains of high LCST: The high temperature and high salinity self-assembly dependence. Carbohydrate Polymers 184: 108-117.

Naik, A., Kalia, Y.N. & Guy, R.H. 2000. Transdermal drug delivery: Overcoming the skin’s barrier function. Pharmaceutical Science & Technology Today 3: 318-326.

Naito, S., Ito, Y., Kiyohara, T., Kataoka, M., Ochiai, M. & Takada, K. 2012. Antigen-loaded DMN array as a novel tool for percutaneous vaccination. Vaccine 30(6): 1191-1197.

Nazmi, N.N., Isa, M.I.N. & Sarbon, N.M. 2017. Preparation and characterization of chicken skin gelatin/CMC composite film as compared to bovine gelatin film. Food Bioscience 19: 149-155.

Pan, J., Ruan, W., Qin, M., Long, Y., Wan, T., Yu, K., Zhai, Y., Wu, C. & Xu, Y. 2018. Intradermal delivery of STAT3 siRNA to treat melanoma via DMNs. Scientific Reports 8: 1117.

Park, D., Park, H., Seo, J. & Lee, S. 2014. Sonophoresis in transdermal drug deliverys. Ultrasonics 54: 56-65.

Prausnitz, M.R. & Langer, R. 2008. Transdermal drug delivery. Nature Biotechnology 26(11): 1261-1268.

Qi, X.M., Liu, S.Y., Chu, F.B., Pang, S., Liang, Y.R., Guan, Y. & Sun, R.C. 2015. Preparation and characterization of blended films from quaternized hemicelluloses and carboxymethyl cellulose. Mater 9(1): 4.

Rahman, N.A., Kamarudin, N.S., Esaa, F., Kalila, M.S. & Kamarudin, S.K. 2019. Bacterial cellulose as a potential hard gelatin capsule. Jurnal Kejuruteraan SI 2(1): 151-156.

Ramli, S., Ja’afar, S.M., Sisak, M.A.A., Zainuddin, N. & Rahman, I.A. 2015. Formulation and physical characterization of microemulsions based carboxymethyl cellulose as vitamin c carrier. Malaysian Journal of Analytical Sciences 19(1): 275-283.

Rani, M., Rudhziah, S., Ahmad, A. & Mohamed, N. 2014. Biopolymer electrolyte based on derivatives of cellulose from kenaf bast fiber. Polymers 6(9): 2371-2385.

Salleh, K.M., Zakaria, S., Sajab, M.S., Gan, S. & Kaco, H. 2019. Superabsorbent hydrogel from oil palm empty fruit bunch cellulose and sodium carboxymethylcellulose. International Journal of Biological Macromolecules131: 50-59.

Salleh, K.M., Zakaria, S., Sajab, M.S., Gan, S., Chia, C.H., Jaafar, S.N.S. & Amran, U.A. 2018. Chemically crosslinked hydrogel and its driving force towards superabsorbent behaviour. International Journal of Biological Macromolecules118: 1422-1430.

Su, J.F., Yuan, X.Y., Huang, Z., Wang, X.Y., Lu, X.Z., Zhang, L.D. & Wang, S.B. 2012. Physicochemical properties of soy protein isolate/carboxymethyl cellulose blend films crosslinked by Maillard reactions: Color, transparency and heat-sealing ability. Materials Science and Engineering: C 32(1): 40-46.

Sullivan, S.P., Murthy, N. & Prausnitz, M.R. 2008. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Advanced Materials 20(5): 933-938.

Tabari, M. 2017. Investigation of carboxymethyl cellulose (CMC) on mechanical properties of cold water fish gelatin biodegradable edible films. Foods 6(6): 41. 

Thakur, R.R.S., Tekko, I.A., Al-Shammari, F., Ali, A.A., McCarthy, H. & Donnelly, R.F. 2016. Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery. Drug. Deliv. Transl. Res. 6(6): 800-815.

Tongdeesoontorn, W., Mauer, L.J., Wongruong, S., Sriburi, P. & Rachtanapun, P. 2011. Effect of carboxymethyl cellulose concentration on physical properties of biodegradable cassava starch-based films. Chemistry Central Journal 5(1): 1-8.

 Tuan-Mahmood, T.M., McCrudden, M.T.C., Torrisi, B.M., McAlister, E., Garland, M.J., Singh, T.R.R. & Donnelly, R.F. 2013. Microneedles for intradermal and transdermal drug delivery. European Journal Pharmaceutical Sciences 50(5): 623-637.

Tong, Q., Xiao, Q. & Lim, L.T. 2008. Preparation and properties of pullulan-alginate-carboxymethylcellulose blend films. Food Research International 41: 1007-1014.

Waghule, T., Singhvi, G., Dubey, S.K., Pandey, M.M., Gupta, G., Singh, M. & Dua, K. 2019. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotheraphy 109: 1249-1258.

Wu, J., Sun, X., Guo, X., Ge, S. & Zhang, Q. 2017. Physicochemical properties, antimicrobial activity and oil release of fish gelatin films incorporated with cinnamon essential oil. Aquacultuure and Fisheries 2(4): 185-192.

Wu, J., Ge, S., Liu, H., Wang, S., Chen, S., Wang, J. & Zhang, Q. 2014. Properties and antimicrobial activity of silver carp (Hypophthalmichthys molitrix) skin gelatin-chitosan films incorporated with oregano essential oil for fish preservation. Food Packaging and Shelf Life 2(1): 7-16.

Yang, J., Liu, X., Fu, Y. & Song, Y. 2019. Recent advances of microneedles for biomedical applications: Drug delivery and beyond. Acta Pharmaceutica Sinica B 9(3): 469-483.

Zhang, Y., Jiang, G., Yu, W., Liu, D. & Xu, B. 2018. Microneedles fabricated from alginate and maltose for transdermal delivery of insulin on diabetic rats. Materials Science and Engineering: C 85: 18-26.

*Pengarang untuk surat-menyurat; email: su_ramli@ukm.edu.my