• International Journal of Technology (IJTech)
  • Vol 13, No 2 (2022)

Preparation, Characterization, and Release Study of Nanosilica/Chitosan Composite Films

Preparation, Characterization, and Release Study of Nanosilica/Chitosan Composite Films

Title: Preparation, Characterization, and Release Study of Nanosilica/Chitosan Composite Films
Nadya Alfa Cahaya Imani, Yuni Kusumastuti, Himawan Tri Bayu Murti Petrus, Daniel Timotius, Nur Rofiqoh Eviana Putri, Mime Kobayashi

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Cite this article as:
Imani, N.A.C., Kusumastuti, Y., Petrus, H.T.B.M., Timotius, D., Putri, N.R.E., Kobayashi, M., 2022. Preparation, Characterization, and Release Study of Nanosilica/Chitosan Composite Films. International Journal of Technology. Volume 13(2), pp. 444-453

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Nadya Alfa Cahaya Imani Department of Chemical Engineering, Faculty of Engineering, Universitas Negeri Semarang, Sekaran Campus, Gunungpati, Semarang, 50229, Indonesia
Yuni Kusumastuti Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Sleman, Yogyakarta, 55281, Indonesia
Himawan Tri Bayu Murti Petrus - Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Sleman, Yogyakarta, 55281, Indonesia - Unconventional Geo-resources Research Center Faculty of Engineering Unive
Daniel Timotius Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Sleman, Yogyakarta, 55281, Indonesia
Nur Rofiqoh Eviana Putri Department of Chemical Engineering, Faculty of Engineering, Universitas Gadjah Mada, Sleman, Yogyakarta, 55281, Indonesia
Mime Kobayashi Division of Biological Science, Nara Institute of Science and Technology, 8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan
Email to Corresponding Author

Abstract
Preparation, Characterization, and Release Study of Nanosilica/Chitosan Composite Films

The development of film materials that can control the release of drugs is needed to create a smart drug delivery system. This paper reports the properties and kinetic studies of film models made of chitosan and nanosilica. Nanosilica was directly incorporated into the chitosan solution to modify and enhance the properties of the composites as potential drug carriers. Fourier transform infrared spectroscopy results acknowledge the successful fabrication of chitosan/nanosilica composite films. Wettability tests showed that the inclusion of nanosilica could make the film more hydrophilic by incorporating up to 5 wt%. The effective diffusion coefficients obtained by mathematical modeling were in the range of 10-6 cm2/min. Based on the kinetic studies, the power-law model is the most suitable model to explain the mechanism of drug released from composite films with kK values ranging from 0.3552 to 0.4279, the value of n in the range of 0.3103 to 0.3955, and the value of R2 in the range of 0.9008 to 0.9411. The overall result concludes that these chitosan/nanosilica composite films have great potential to be used as materials for drug carriers.

Chitosan; Composite Film; Drug delivery system; Kinetic model; Nanosilica

Introduction

Medicine is an important component of human healthcare as it is a way to provide therapeutic or healing effects for various diseases (Whittam et al., 2016). Conventionally, drugs have been administered to the body through the gastrointestinal tract, rectal injection, or directly into a vein (Batchelor and Marriott, 2013). These methods are inherently less effective because, at each time of administration, a large dose of the drugs has to be given for the drugs to reach the target locations (Wen et al., 2015). Drug administration must be repeated and often cause side effects. Side effects can be allergies or systemic poisoning caused by reactions between the drugs and stomach fluids or the patient’s blood. To avoid repeated drug administrations to patients so as to minimize the possibility of poisoning caused by excessive drug doses, a drug delivery system that can deliver controlled drug release is needed.     

One of the most studied drug delivery systems is the use of a polymer film (thin membrane layer). This form of film has the advantage of being flexible in how it is administered to the body (Chan et al., 2019; Hatanaka et al., 2019). The drug delivery system in the form of films usually uses polymers from natural materials (biopolymers) as the matrix because these materials have biocompatible properties (properties where a material does not cause rejection reactions by the human immune system that detect and attack foreign objects), are biodegradable (the ability of a material to be degraded inside the body), and are nontoxic (Chan et al., 2019; Kalantari et al., 2019; Samadian et al., 2020). One biopolymer that has been gaining attention for this purpose is chitosan. Chitosan is a natural polysaccharide and a derivative of chitin, which can be found in the exoskeleton of shelled animals (crustaceans) (Sedaghat et al., 2017). This compound has antibacterial properties, is nontoxic, and is easy to modify, so it is often chosen to be used for various applications in the fields of food,  textiles, waste treatment, agriculture, and health (Revathi and Thambidurai, 2017; Mohamed et al., 2018; Kamdem et al., 2019; Si et al., 2019). Chitosan is also a polymer that has a positive charge (polycation), which makes it good to be used as a matrix for drug delivery systems in the form of a film because it will increase the adhesive properties (ability to stick) of the film (Krisanti et al., 2020; Singh et al., 2020). In its application as a film for drug delivery, like other biopolymers, chitosan has a disadvantage that it is easy to swell; that is, swelling occurs when the film is in a liquid system. This swelling can cause discomfort when the patient uses this film-shaped drug release system. In addition, a high swelling rate will trigger an initial burst release (rapid drug release at the beginning) (Ammar et al., 2009). Therefore, efforts are needed to modify the film from this material to improve its characteristics, especially for applications as a  delivery system of drugs or other components.
      One way to increase the ability of chitosan film as a drug delivery system is by adding inorganic materials. According to Uragami et al. (2002) and Kusumastuti et al. (2017), the formation of an organic–inorganic film could create a vastly functional materials by combining the film-forming properties of organic polymers and the stability and strength of inorganic compounds. Furthermore, the potential use of organic/inorganic composites as biomaterials in tissue engineering has been reported by Kusumastuti et al. (2018). Also, research conducted by Liu et al. (2019) reported that the addition of an inorganic material, namely nanosilica, can decrease the percentage swelling of the chitosan film and increase the tensile strength of the film. Nanosilica is used because this material has properties such as nontoxic, large drug loading capacity, easy to modify, and biocompatible (Bharti et al., 2015). Another similar study was also conducted by Wu et al. (2019), where mesoporous silica was obtained from tetraethyl orthosilicate and it was added to chitosan for making films, which are able to be applied for food packaging application. The results of the study showed that the prepared hybrid films can slow the release of curcumin and have good antimicrobial activity.
        Herein, film as a drug delivery system was prepared by mixing chitosan and nanosilica powder. Curcumin, which is known to have potential as an anticancer drug, was used as a model drug for drug release. Nanosilica addition aimed to modify the structure of the chitosan film so that it can increase resistance to control the speed of drug release. In this study, we report the properties of the films that have been made and investigated their potential as a controlled drug delivery system. Furthermore, we also report mathematical modeling and kinetic studies of drug release from the film. Thus, a simple thin-film model can be obtained and used to foresee the drug release profile of a system for wound dressing. 

Conclusion

Composite films made of nanosilica and chitosan have been successfully prepared by varying the ratio of the amount of nanosilica to chitosan. The addition of nanosilica to the film matrix up to 5% by weight of nanosilica/weight of chitosan increased the hydrophobic properties of the film. However, higher nanosilica content led to smaller WCA values or more hydrophilic films. Performance tests on drug release show that all films containing a mixture of nanosilica have higher drug-retaining ability than films made only with chitosan. The calculation results show that the effective diffusion values of chitosan/nanosilica films are in the range of 4.1935 ´ 10-to 9.9372 ´ 10-6 cm2/min and the most suitable drug release mechanism follows the power-law model with R2 value ranging from 0.9008 to 0.9411. From the results, it can be stated that chitosan and nanosilica composites have great potential to be used as materials for drug carriers. However, further study of the optimal methods and conditions for film formation is needed to make this controlled drug delivery system even more effective.

Acknowledgement

        The authors appreciate and acknowledge the partial financial support provided by the Global Collaboration Program of the Nara Institute of Science and Technology (FY2016-2018) sponsored by MEXT, Japan.

References

Ammar, H.O., Ghorab, M., Kamel, R., 2009. Polymeric Matrix System for Prolonged Delivery of Tramadol Hydrochloride, Part I?: Physicochemical Evaluation. AAPS Pharmaceutical Science and Technology, Volume 10(1), pp. 7–20. doi: 10.1208/s12249-008-9167-0

Barleany, D.R., Ananta, C.V., Maulina, F., Rochmat, A., Alwan, H., Erizal, 2020. Controlled Release of Metformin Hydrogen Chloride from Stimuli-Responsive Hydrogel Based on Poly(N-Isopropylacrylamide)/Chitosan/Polyvinyl Alcohol Composite. International Journal of Technology, Volume 11, pp. 511–521. doi: 10.14716/ijtech.v11i3.2330

Batchelor, H.K., Marriott, J.F., 2013. Formulations for Children: Problems and Solutions. British Journal of Clinical Pharmacology, Volume 79(3), pp. 405–418. doi: 10.1111/bcp.12268

Bharti, C., Gulati, N., Nagaich, U., Pal, A., 2015. Mesoporous Silica Nanoparticles in Target Drug Delivery System: A Review. International Journal of Pharmaceutical Investigation, Volume 5(3), pp. 124–133. doi: 10.4103/2230-973X.160844

Bruschi, M.L., 2015. Mathematical Models of Drug Release. Elsevier, United Kingdom. doi: 10.1016/B978-0-08-100092-2.09993-8

Chan, S.Y., Goh, C.F., Lau, J.Y., Tiew, Y.C., Balakrishnan, T., 2019. Rice Starch Thin Films as a Potential Buccal Delivery System: Effect of Plasticiser and Drug Loading on Drug Release Profile. International Journal of Pharmaceutics, Volume 562, pp. 203–211. doi: 10.1016/j.ijpharm.2019.03.044

Dash, S., Murthy, P.N., Nath, L., Chowdhury, P., 2010. Kinetic Modeling on Drug Release from Controlled Drug Delivery Systems. Acta Poloniae Pharmaceutica, Volume 67(3), pp. 217–223

Dwivedi, C., Pandey, I., Pandey, H., Ramteke, P.W., Pandey, A.C., Mishra, S.B., Patil, S., 2017. Electrospun Nanofibrous Scaffold as a Potential Carrier of Antimicrobial Therapeutics for Diabetic Wound Healing and Tissue Regeneration. In: Nano- and Microscale Drug Delivery Systems, Grumezescu, A.M., (ed.), Elsevier, United Kingdom, pp. 147–164. doi: 10.1016/B978-0-323-52727-9.00009-1

Fahim, I.S., Mamdouh, W., Salem, H.G., 2015a. Chitosan Nanocomposite Mesoporous Membranes: Mechanical and Barrier Properties as a Function of Temperature. Journal of Materials Science Research, Volume 4(4). doi: 10.5539/jmsr.v4n4p1

Fahim, I.S., Marei, N., Salem, H.G., Mamdouh, W., 2015b. Effect of Graphene and Fullerene Nanofillers on Controlling the Pore Size and Physicochemical Properties of Chitosan Nanocomposite Mesoporous Membranes. Journal of Nanomaterials, Volume 2015. doi: 10.1155/2015/979561

Hatanaka, T., Saito, T., Fukushima, T., Todo, H., Sugibayashi, K., Umehara, S., Takeuchi, T., Okamura, Y., 2019. Potential of Biocompatible Polymeric Ultra-Thin Films, Nanosheets, as Topical and Transdermal Drug Delivery Devices. International Journal of Pharmaceutics, Volume 565, pp. 41–49. doi: 10.1016/j.ijpharm.2019.04.059

Hazra, K., Kumar R., Sarkar, B.K., Chowdary, Y.A., Devgan, M., Ramaiah, M., 2015. UV-Visible Spectrophotometric Estimation of Curcumin in Nanoformulation. International Journal of Pharmacognosy, Volume 2(3), pp. 127–130. doi: 10.13040/IJPSR.0975-8232

Imani, N.A.C., 2018. Pengaruh Penambahan Nanosilika terhadap Karakter Fisik Film Kitosan serta Kecepatan Pelepasan Kurkumin. Master’s Thesis, Graduate Program, Department of Chemical Engineering, Universitas Gadjah Mada, Yogyakarta, Indonesia

Kalantari, K., Afifi, A.M., Jahangirian, H., Webster, T.J., 2019. Biomedical Applications of Chitosan Electrospun Nanofibers as a Green Polymer—Review. Carbohydrate Polymers, Volume 207, pp. 588–600. doi: 10.1016/j.carbpol.2018.12.011

Kamdem, D.P., Shen, Z., Nabinejad, O., 2019. Development of Biodegradable Composite Chitosan-Based Films Incorporated with Xylan and Carvacrol for Food Packaging Application. Food Packaging and Shelf Life, Volume 21, pp. 100344. doi: 10.1016/j.fpsl.2019.100344

Krisanti, E.A., Lazuardi, D., Kiresya, K.K., Mulia, K., 2020. Tablet Formulation Containing Chitosan-Alginate Microparticles: Characterization and Release Profile of Xanthones. International Journal of Technology, Volume 11(5), pp. 900–909. doi: 10.14716/ijtech.v11i5.4338

Kusumastuti, Y., Petrus, H.T.B.M., Fiska, Y., 2017. Synthesis and Characterization of Biocomposites Based on Chitosan and Geothermal Silica. AIP Conference Proceedings, Volume 1823, pp. 020127. doi: 10.1063/1.4978200

Kusumastuti, Y., Kobayashi, M., Purwaningtyas, F., Najmina, M., Petrus, H.T.B.M., Putri, N.R.E., Budhijanto, Tanihara, M., 2018. Characterization of Three Dimensional Scaffolds from Local Chitosan/Alginate/Geothermal Silica for Potential Tissue Engineering Applications. Journal of Engineering Science and Technology, Volume 13(11), pp. 3500–3515

Liu, Y., Cai, Z., Sheng, L., Ma, M., Xu, Q., 2019. Influence of Nanosilica on Inner Structure and Performance of Chitosan Based Films. Carbohydrate Polymers, Volume 212, pp. 421–429. doi: 10.1016/j.carbpol.2019.02.079

Mohamed, M.H., Ajaero, C., McMartin, D.W., Peru, K.M., Friesen, V., Simair, M., Headley, J.V., Wilson, L.D., 2018. Solubilized Chitosan Biopolymers for Sequestration of Organic Acids in Aquatic Environments after Biodegradation in a Constructed Wetland Treatment System. International Journal of Technology, Volume 9, pp. 1140–1150. doi: 10.14716/ijtech.v9i6.2301

Rallini, M., Kenny, J.M., 2017. Nanofillers in Polymers. In: Modification of Polymer Properties, Elsevier, United Kingdom, pp. 47–86

Revathi, T., Thambidurai, S., 2017. Synthesis of Chitosan Incorporated Neem Seed Extract (Azadirachta indica) for Medical Textiles. International Journal of Biological Macromolecules, Volume 104, pp. 1890–1896. doi: 10.1016/j.ijbiomac.2017.02.081

Samadian, H., Maleki, H., Allahyari, Z., Jaymand, M., 2020. Natural Polymers-Based Light-Induced Hydrogels: Promising Biomaterials for Biomedical Applications. Coordination Chemistry Reviews, Volume 420, pp. 213432. doi: 10.1016/j.ccr.2020.213432

Sedaghat, F., Yousefzadi, M., Toiserkani, H., Najafipour, S., 2017. Bioconversion of Shrimp Waste Penaeus merguiensis Using Lactic Acid Fermentation: An Alternative Procedure for Chemical Extraction of Chitin and Chitosan. International Journal of Biological Macromolecules, Volume 104, pp. 883–888. doi: 10.1016/j.ijbiomac.2017.06.099

Si, J., Yang, Y., Xing, X., Yang, F., Shan, P., 2019. Controlled Degradable Chitosan/Collagen Composite Scaffolds for Application in Nerve Tissue Regeneration. Polymer Degradation and Stability, Volume 166, pp. 73–85. doi: 10.1016/j.polymdegradstab.2019.05.023

Singh, G., Nayal, A., Malhotra, S., Koul, V., 2020. Dual Functionalized Chitosan Based Composite Hydrogel for Haemostatic Efficacy and Adhesive Property. Carbohydrate Polymers, Volume 247, pp. 116757. doi: 10.1016/j.carbpol.2020.116757

Timotius, D., Kusumastuti, Y., Imani, N.A.C., Rochmadi, Putri, N.R.E., Rahayu, S.S., Wirawan, S.K., Ikawati, M., 2020. Kinetics of Drug Release Profile from Maleic Anhydride-Grafted-Chitosan Film. Materials Research Express, Volume 7(4), pp. 046403. doi: 10.1088/2053-1591/ab80d9

Uragami, T., Okazaki, K., Matsugi, H., Miyata, T., 2002. Structure and Permeation Characteristics of an Aqueous Ethanol Solution of Organic–Inorganic Hybrid Membranes Composed of Poly(Vinyl Alcohol) and Tetraethoxysilane. Macromolecules, Volume 35(24), pp. 9156–9163. doi: 10.1021/ma020850u

Wen, H., Jung, H., Li, X., 2015. Drug Delivery Approaches in Addressing Clinical Pharmacology-Related Issues: Opportunities and Challenges. AAPS Journal, Volume 17(6), pp. 1327–1340. doi: 10.1208/s12248-015-9814-9

Whittam, A.J., Maan, Z.N., Duscher, D., Wong, V.W., Barrera, J.A., Januszyk, M., Gurtner, G.C., 2016. Challenges and Opportunities in Drug Delivery for Wound Healing. Advances in Wound Care, Volume 5(2), pp. 79–88. doi: 10.1089/wound.2014.0600

Wu, C., Zhu, Y., Wu, T., Wang, L., Yuan, Y., Chen, J., Hu, Y., Pang, J., 2019. Enhanced Functional Properties of Biopolymer Film Incorporated with Curcurmin-Loaded Mesoporous Silica Nanoparticles for Food Packaging. Food Chemistry, Volume 288, pp. 139–145. doi: 10.1016/j.foodchem.2019.03.010