Alginic acid/graphene oxide hydrogel film coated functional cotton fabric for controlled release of matrine and oxymatrine

Abstract

The present study describes the fabrication of a functional cotton fabric in which an alginic acid/graphene oxide hydrogel layer was coated on the surface of cotton fabric. The functional fabric was then used to absorb and release two classic Chinese traditional drugs, matrine and oxymatrine, to investigate the controlled release capability of the functional fabric. The obtained results indicated that the prepared functional fabric has a sandwich structure. This structure significantly enhanced the absorbing capability of the cotton fabric for both water and the two drugs. Moreover, with the incorporation of the graphene oxide, the functional cotton fabric could steadily release the absorbed drugs and prevent burst release. It was also found that the release speed of the two drugs could be controlled through tuning the environmental temperature. The prepared functional cotton fabric has large application potentials in many external medical care fields.

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1. Introduction

Matrine and oxymatrine (see structures in Fig. S1†), two quinolizidine alkaloids, have been viewed as two significant Chinese traditional drugs which are extracted from the dried root of Sophora Flavescenes Ait.^1,2 They have found various medical applications for the treatment of viral hepatitis, chronic hepatitis, leukemia, myocarditis, tumors, cancer etc. through regulating the immune reaction inside the human body.^3,4 Besides the clinical practice of oral administration, matrine and oxymatrine have been found to have anti-hypersensitive and anti-inflammation effects in human skin which inhibit the growth and spread of fungus and virus.⁵ Hence, matrine and oxymatrine have been extensively studied recently for application for skin diseases like psoriasis, dermatitis and eczema using external therapy approaches.^6,7

In recent decades, the designing and preparation of hydrogel systems for functionalized drug delivery applications have excited numerous research interests.^8–11 Being non-toxic, biocompatible and biodegradable, natural polysaccharide polymers have been extensively used as the hydrogel raw materials, among which the alginic acid (AA) is one of the most commonly used candidates.^12–15 However, the main defect of these biopolymer hydrogel is the weak interactions between the biopolymer and the target drug which might result in a burst release speed during the therapy process.^16,17 The graphene oxide (GO) is thus a desirable material to be incorporated into the hydrogel system for capturing the drug molecules and controlling the release speed since GO has a fused ring structure and contains a lot of oxygen containing functional groups within its structure.^18–23 Many studies have shown that the incorporation of GO could enhance the drug encapsulation and delivery capability of the hydrogel systems.^24–26 Furthermore, the cotton fabric also has exceptionally high absorption ability since it has a porous microstructure and abundant functional groups within its cellulose molecules.^27,28 Thus the alginate/GO hydrogel incorporated cotton fabric is potential to be a promising system for drug encapsulating and release.

Hence, in this study, the sodium agninate/GO hydrogel film (SA/GO) coated cotton fabric (AG-CF) was prepared through a wet coating approach. The drug delivery properties of the prepared functional fabric were then studied in which the matrine and oxymatrine were selected as the drug candidates. Compared with the neat cotton and pure SA coated cotton fabric, the AG coated functional fabrics had a higher absorption efficiency to the two selected drugs. Moreover, the AG coated functional fabrics could control the release of the matrine and oxymatrine more steadily than the pure SA coated cotton fabric. The functional cotton fabric prepared in this study has potentials in fabricating face mask or plaster for external applications like steaming therapy and hot compress therapy with drugs.

2. Experimental

2.1 Materials

Natural graphite powder was purchased from Aldrich (America). Sodium alginate (SA, viscosity 350–550 mPa s) was purchased from Acros (Belgium). Pure matrine and oxymatrine (purity ≥99.0%) was supplied by Beijing Yonge Water Biological Technology Co., Ltd. (China). 100% cotton fabric (CF, 33 wrap × 64 weft per inch, ∼1 mm of thickness) was purchased from Dalian 2nd Cotton Mill (China). Other reagents were of analytical grade and used as received without further purification. Deionized water (H₂O) was used exclusively in this study.

2.2 Preparation of AG-CF

The GO was prepared from natural graphite powder using modified Hummer's method described elsewhere.¹⁸ The typical procedure of preparing the AG-CF was processed as follows. Certain amount of GO was first put into 20 mL of H₂O and sonicated for 2 h to obtain a uniform dispersion. At the same time, 0.5 g SA was dissolved in 30 mL of H₂O with continuous mechanical stirring until a transparent SA solution was obtained. After the GO dispersion was added, the resulted solution was stirred for another 1 h. The CF (10 cm × 2 cm in shape, 0.32 g) which has been immersed in 50 mL of H₂O for 10 min was then dipped into the SA/GO solution and taken out quickly. The SA/GO coated CF was then quickly put into 100 mL of 10 M CaCl₂ solution with gentle magnetic stirring. After 10 min of crosslinking, the SA/GO hydrogel coated CF was taken out and washed with H₂O for three times to remove the uncrosslinked SA/GO and the CaCl₂ residual. Finally, the AG-CF composites with GO content of 0.5 wt% and 1.0 wt% were obtained and named as AG0.5-CF and AG1.0-CF, respectively. For comparison, pure SA hydrogel coated CF was also prepared following similar procedures and named as AG0-CF. After the AG-CF was freeze-dried and weighed, it was calculated that for a 10 cm × 2 cm rectangular CF sample (0.32 g), the weight of the hydrogel adhered on the CF was ∼0.06 g. The schematic illustration for the preparation of AG-CF was shown in Fig. 1.

Fig. 1 Schematic illustration of AG-CF preparation.

2.3 Characterizations

Scanning electron microscopy (SEM) was conducted by the JEOL SEM 6490. The composites samples were freeze dried first before testing. Fourier transform infrared (FT-IR) spectra of the samples were recorded using a Perkin Elmer 100 spectrophotometer with a resolution of 4 cm⁻¹ and 16 scans. The matrine and oxymatrine concentrations were quantified by high performance liquid chromatography (HPLC) using a Waters 2489 spectrometer with a Brava C18-BDS column (5 μm, 25 × 0.46 cm) exclusively. The absorption wavelength of 230 nm was selected for detection and the mobile phase was a mixture of 80% acetonitrile, 19.9% H₂O and 0.1% phosphoric acid.

The swelling ratio (SR, %) of freeze-dried AG-CF samples was conducted by immersing the samples in 100 mL of H₂O for 18 h at 25 °C to reach the equilibrium. The SR was calculated as:

where m₀ is the mass weight of the initially freeze-dried AG-CF samples and m_t is the mass ratio of the swollen ones.

2.4 Drug encapsulating and release study

The hydrogel coated fabric sample (10 cm × 2 cm) was submerged into 50 mL of 0.5 mg mL⁻¹ drug solution. The solution was stirred at room temperature until the equilibrium was reached. During the encapsulating process, the drug solution samples were withdrawn at predetermined intervals and analyzed with the HPLC spectrometer.

Thereafter, the fabric sample was taken out of the drug solution and washed with H₂O for several times to remove the unabsorbed drug. The fabric sample was then immersed in a conical flask with 50 mL of release medium (20 mM sodium phosphate buffer solution with pH 7.4). The conical flask was then incubated at 25 ± 0.1 °C, 37 ± 0.1 °C and 60 ± 0.1 °C respectively with constant shaking at 100 rpm (Grant OLS200 Shaking water bath machine). At predetermined time intervals, the solution sample were collected from the release medium and replaced by equal quantity of fresh release medium. The collected samples were analyzed by the HPLC spectrometer.

3. Results and discussion

The morphology of the AG-CF was investigated first. Fig. 2 shows the SEM images of the AG-CF. As could be seen, a thin layer of AG hydrogel film was coated on the surface of the CF. From the magnified SEM image of the AG film shown in Fig. 2(b), it could be seen that the AG hydrogel film had a porous structure with abundant small holes. The porous structure enables the AG-CF with molecule encapsulating and delivery capability. The digital image shown in Fig. S2† also revealed that the hydrogel film was uniformly embedded on the surface of the CF.

Fig. 2 (a) SEM image and (b) magnified SEM image of AG-CF.

Fig. 3 shows the FT-IR spectra of the neat cotton fabric, AG0-CF, AG0.5-CF and AG1.0-CF. It has been known that the forming principle of the alginate hydrogel using CaCl₂ as the crosslinking agent was the ionic cross-linking via Ca²⁺ bridges between the L-guluronic acid residues on adjacent chains of the alginate. Thus, the alginate hydrogel can be fabricated in various forms, like spheres and fibers, bulks, and the film in the present study. As shown, the neat CF had a broad peak at ∼3292 cm⁻¹. Since the CF was composed of cellulose structure with abundant –OH groups, this peak was attributed to the stretching vibration of the –OH group. The SA hydrogel had two characteristic peaks at ∼1627 cm⁻¹ and 1435 cm⁻¹, which were assigned to the symmetric and asymmetric COO⁻ stretching vibration of the carboxylate salt group. When the GO was incorporated into the SA, the –OH vibration peak shifted from 3410 cm⁻¹ to 3372 cm⁻¹, indicating a hydrogen interactions between the SA and GO. After the hydrogel was coated onto the CF surface, the peak at ∼3292 cm⁻¹ shifted to a smaller wavelength position (∼3267 cm⁻¹), indicating the CF and the SA had hydrogen bonding interactions. When the GO was incorporated into the system, the resulting –OH vibration peak broadened and had a further shift to smaller wavelengths at ∼3234 cm⁻¹ and 3175 cm⁻¹, which meant the GO generated more hydrogen bonding. Besides, the COO⁻ vibration peak also shifted to smaller wavelength at 1422 cm⁻¹, which further demonstrated the presence of the hydrogen bonding and the existence of the interactions between the hydrogel film and the CF.

Fig. 3 FT-IR spectra of SA hydrogel, AG1.0 hydrogel, neat cotton fabric, AG-0CF, AG0.5-CF and AG1.0-CF.

The swelling capacity is of significance for evaluating the structure of the AG-CF system. Fig. 4 shows the swelling properties of the AG-CF samples. Generally, the SR for AG hydrogel was from 20–50.²⁹ In the present study, the SRs for AG0, AG0.5 and AG1.0 were 43.8, 35.3 and 31.2 respectively, as shown in Fig. S3.† Compared with AG0, the decrease in SR of AG0.5 and AG1.0 was because the incorporation of the GO induced a higher crosslinking degree which restricted the adsorption of the hydrogel molecules to the H₂O. It could be seen from Fig. 4 that all hydrogel coated CF samples reached their equilibrium when being put into the H₂O for around 9 h.

Fig. 4 The swelling properties of AG0-CF, AG0.5-CF and AG1.0-CF.

Moreover, Table 1 gives the detailed water absorbing weight of all the samples. It could be seen that since the AG hydrogel film only occupied ∼15 wt% of the AG-CF, the AG-CF actually absorbed three times of water amount compared with the AG hydrogel. The water was retained in the AG-CF system due to the existence of the hydrogel film. From Fig. 4 and Table 1, it could be also observed that the AG0.5-CF and AG1.0-CF had higher SR than AG0-CF. This might because in the AG-CF system, the cotton fabric had the main contribution to the water adsorption since the cotton had porous microstructures and took up ∼85% mass content of the AG-CF. Although for pure hydrogel, the AG0.5 and AG1.0 had smaller SR, the existence of the GO in the AG0.5-CF and AG1.0-CF could provide much more functional oxygen groups which could stabilize more adsorbed H₂O molecules for a long period of time, resulting a relatively higher SR. Thus, the abundant functional groups contained in the AG hydrogel film help the CF store more water within the CF when the absorbing equilibrium was reached.

Table 1 Detailed swelling ratio values of the AG samples and AG-CF samples

Sample name	Swelling ratio (SR)	m(AG) (g)	m(CF) (g)	H2O absorbed (g)	m(H2O)/m(AG)
AG0	43.8	0.06	0	2.568	42.8
AG0.5	35.3	0.06	0	2.058	34.3
AG1.0	31.2	0.06	0	1.812	30.2
AG0-CF	14.8	0.06	0.32	5.244	87.4
AG0.5-CF	15.6	0.06	0.32	5.548	92.5
AG1.0-CF	15.4	0.06	0.32	5.472	91.2

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The drug encapsulating and release behavior of the AG-CF samples were then investigated. Fig. 5 shows the drug encapsulating efficiency of the AG-CF samples, in which the matrine and oxymatrine were used as the target drug. Table 2 also gives the detailed values of the drug encapsulating efficiency. It could be observed that the drug loaded by the samples was dramatically affected by the AG coating. Since pure CF had no AG coating, the CF quickly got the absorption equilibrium within 3 hours of time. Moreover, without the AG layer, the drug loaded could not be retained within the CF structure. The hydrogel film here acted as a bridge and pathway which the drugs can be stored by the cotton fabric and released afterwards. It is well known that the hydrogel system is a promising candidate for the encapsulation and release of the drugs. Without the coating of the alginate hydrogel film, the pure cotton fabric can not hold sufficient drugs within its structure also it had high absorption ability. Meanwhile, for AG-CF samples, the micropores of the AG hydrogel acted as a gate to tune the loading speed of both the matrine and oxymatrine, in which the drug encapsulating process was much steadier.³⁰

Fig. 5 The equilibrium loaded (a) matrine and (b) oxymatrine amount in neat CF, AG0-CF, AG0.5-CF and AG1.0-CF.

Table 2 Detailed values of matrine encapsulating efficiency of the AG-CF samples (for a 10 cm × 2 cm sample in 50 mL of 0.5 mg mL⁻¹ drug solution)

Sample name	Encaps. matrine (mg)	Matrine content (mg g^−1)	Encaps. oxymatrine (mg)	Oxymatrine content (mg g^−1)
CF	2.56	8.0	2.59	8.1
AG0-CF	11.3	29.8	11.7	30.8
AG0.5-CF	15.4	40.4	16.8	44.3
AG1.0-CF	16.5	43.3	18.4	48.6

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The encapsulating efficiency was also affected much by the existence of the GO. As could be seen from Fig. 5 and Table 2, the incorporation of the GO remarkably enhanced the ultimate drug loading amount in the AG-CF samples. Moreover, with the increase of the GO amount in the AG hydrogel, the drug amount encapsulated also increased. Since the GO contained a lot of oxygen containing groups within its structure like –OH groups and –COOH groups, these groups could interact with the matrine and oxymatrine. The interactions facilitated the encapsulating of the AG0.5-CF and AG1.0-CF sample to the two drugs. It was also found that the encapsulating efficiency of the AG-CF samples to oxymatrine was higher than that of the matrine. From the structure of the matrine and oxymatrine (Fig. S1†), it could be observed that due to the existence of the oxygen ion, the polarity of the oxymatrine is higher than the matrine. Based on this fact, the oxymatrine interacted better with the GO through n–π stacking, resulting in a better encapsulating efficiency to that of the marine.

The drug release behavior of the AG-CF samples under different temperatures was then investigated. Fig. 6–8 show the cumulate release of matrine and oxymatrine from different CF samples under 25 °C, 37 °C and 60 °C. Table S1† also shows the detailed release rate of these two drugs. The reason why these three temperatures were chosen was that 25 °C was near room temperature, 37 °C was near body temperature, and 60 °C was near the highest heating temperature which human body could bear.

Fig. 6 Cumulate release of (a) matrine and (b) oxymatrine from neat CF, AG0-CF, AG0.5-CF and AG1.0-CF at 25 °C.

Fig. 7 Cumulate release of (a) matrine and (b) oxymatrine from neat CF, AG0-CF, AG0.5-CF and AG1.0-CF at 37 °C.

Fig. 8 Cumulate release of (a) matrine and (b) oxymatrine from neat CF, AG0-CF, AG0.5-CF and AG1.0-CF at 60 °C.

It could be seen from Fig. 6 to Fig. 8 that under all three temperatures, the neat CF released all the drugs within 2 hours, and the speed was very fast and uncontrollable. It is known that the cotton fabric has numerous oxygen containing groups which could adsorb drugs. However, without the hydrogel coating, the loaded drugs are quickly released in a limited period of time. For AG-CF samples, the speeds for all release processes were steadier compared with the neat CF, indicating that the AG hydrogel coating layer was able to lower down the release speed of both the matrine and oxymatrine. For AG0-CF, the release equilibrium was reached within 12 h of time and all six release rates were higher than 80%. Meanwhile, for AG0.5-CF and AG1.0-CF, a steady release of the matrine and oxymatrine could be achieved, indicating that the introduction of GO into the functional fabric system inhibited the release of the drugs. Moreover, it could be also seen that at different temperatures, the release speeds of the drugs distinguished much. At 25 °C, less than 50% of the drugs were released, both for AG0.5-CF and AG1.0-CF. When the temperature reached higher, the drug release rated increased at the same time. At temperature of 60 °C, ∼90% of the drugs loading in the functional fabric samples could be released. Thus, after a whole drug release process, the residual drugs loaded in the cotton fabric can be washed out when the water temperature was higher than 60 °C, and the cotton fabric can be ready for next-time drug loading, which achieved a recycle use. The GO amount also affected the release speed, in which more GO delayed more of the drug release. It could be found from the results that the release speed of the drugs can be well controlled through tuning the release temperature and the GO incorporation amount. Thus, it can be conclude that the hydrogel coating here made the drugs to be released steadily when certain temperature was reached. The function of the GO incorporation into the SA hydrogel coating was to tune the release speed of the functional cotton fabric.

It could be also found that the release speed of the oxymatrine was slower than that of the matrine, in which the functional fabric took about 22 h to reach the matrine release equilibrium while took about 26 hour to reach the oxymatrine release equilibrium. This was also due to the better interactions between the GO and oxymatrine which delay the release speed of the oxymatrine. Based on the above discussion, the mechanism why heat triggered the drug release was that the drugs were encapsulated and trapped in the cotton fabric by the AG hydrogel coating, in which the GO interacted with the encapsulated drugs. When the temperature increased, the thermal energy surpassed the interaction energy such as hydrogen bonding, p–π interactions, π–π interactions and van der Vaal forces. The drugs then released from the cotton fabric to the external environment through the AG hydrogel film. The tuning of the GO amount was actually tuning the interaction energy which affected the release temperature and drug release amounts.

The overall results indicated that compared with the neat fabric, the prepared AG-CF functional fabric could remarkable reduce the release speed of the matrine and oxymatrine, and prevent the burst release of drugs caused by the pristine fabric. The introduction of GO also caused a much steady release of the drugs. As the fabric based materials, the prepared AG-CF samples have very good application potentials as the face mask or plaster for external applications like steaming therapy and hot compress therapy with drugs.

4. Conclusions

To conclude, the functional cotton fabric was fabricated through coating the alginate/GO hydrogel onto the surface of the cotton fabric and was used to absorb and release drugs. The results show that the AG-CF functional fabric had a sandwich structure. The introduction of the GO into the system significantly influenced the swelling behavior of the functional fabric. Furthermore, the AG-CF functional fabric could effectively absorb the drugs, matrine and oxymatrine, from the drug solutions. More importantly, the prepared AG-CF functional fabric could release the drugs steadily, preventing the commonly observed drug burst release. Through tuning the release temperature and the incorporation amount of GO, the release speed could be controlled. The cotton fabric based AG-CF fabricated in this study has wide application potentials in the field of external medical applications, such as the face mask or plaster.

Acknowledgements

This work was supported by Natural Science Foundation of Jiangsu Province, China (BK20160938), Students Practice Innovation Program of Nanjing Forestry University (DXSKC-201607), Top-notch Academic Programs Project of Jiangsu Higher Education Institutions (TAPP) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra15543j

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