|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|
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
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.
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 ´ 10-6 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.
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.
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