Introduction

Colon disease was part of the major diseases which significantly harmed human health in the world at present, which included colorectal cancer, Amoeba intestinal disease, acute bacterial dysentery and colon polyps and so on [1, 2]. Conventional treatment such as chemotherapy and radiation therapy had some proven disadvantages, such as lack of spot specificity and exposure control [3]. The oral administration as the principal method was widely used, because of that it had good adaptability, controllability, and simplicity, compared with the other methods. In order to form a more effective colon specificity delivery system by the oral route, many drugs encapsulated system based on microparticle systems, inorganic nanometers and polymer systems had been reported [4,5,6,7]. The development of oral colonic drug delievery system (OCDDS) mainly included the following systems: (1) Time-delay release drug system; (2) pH sensitive release system; (3) Enzyme responsive release system; (4) Pressure dependent release system, etc. [8,9,10,11]. The enzymatic responsive release system had been extensively used due to its specific characteristics of the “key and lock” principle. Since the colony had many unique bacteria that produced unique enzymes. Their specific degradation of some macromolecular materials (such as pectin, guar gum and azo polymers) can lead to a specific release of the drug in the colon. There was also a guarantee for drugs didn’t release in the gastrointestinal tract due to the lack of the corresponding enzymes [12,13,14,15].

Pectin was a kind of vital substance which was suitable for enzyme response system and had good enzyme sensitivity. Pectin was a non-starch polysaccharide material extracted from many plant cell walls, which was a kind of medicine auxiliary material with wide source, low price and no toxicity [16,17,18,19,20]. But pectin was soluble in water and cannot effectively protect the drug, and its calcium salt is not soluble in water. Moreover, it also had the same properties as pectin, which can be degraded by specific enzymes in the colon. Pectin calcium gel was composed of pectin molecular free carboxyl combined with calcium ion by electrostatic force [21]. Therefore, in-depth study the structure improvement of pectin calcium gel could help to solve the problem existing in the application of pectin calcium gel. Nevertheless enzymatic responsive OCDDS for pectin still had some disadvantages. Enzymatic responsive OCDDS for pectin still showed leakage of drugs even in the absence of colonic enzymes for the diffusion time. Moreover, it cannot make the drug release as soon as possible under the action of bacteria [22,23,24,25,26]. So the pectin calcium colonic targeting delivery system was particularly needed to be improved to solve the above problems.

In recent years, the emergence of carbon materials (such as porous carbon, Multi-walled carbon nanotubes and related composites) had put forward more new ideas and ideas are for the development of OCDDS [27, 28]. In particular, Multi-walled carbon nanotubes as suitable drug carriers had showed many remarkably advantages, such as well as high surface area, biocompatibility and efficient absorption by mammalian cells. A large amount of research work has been devoted to clarifying the potential danger of carbon nanotubes as a drug carrier to the human body. The existing experimental data on the toxicity of carbon nanotubes is still incomplete and the experimental results are inconsistent. The study found that carbon nanotubes have an inhibitory effect on the growth of human embryonic kidney cell line HEK293, which can induce apoptosis and reduce cell adhesion [29], and can also cause keratinocyte damage [30]. However, some study also indicated that the commercial single-walled and MCNT have no acute toxic effects on the activity of rat alveolar giant salivary cell line NR8383 and human lung cancer cell line A459 [31]. In addition MCNT of 0.3–5 mg/m3 did not cause significant lung inflammation and tissue damage [32]. The main reason for the divergence of these toxicity experiments is that different researchers use different detection methods, and the carbon nanotubes used in the experiments are different. Therefore, the experimental results are inconsistent. In addition, the research on MCNT is mainly a non-oral administration route. So, the toxicity is also inconclusive. MCNT are another allotrope of carbon found, and its radial dimension is small. MCNT are considered to be a typical one-dimensional nanomaterial. The unique structure of MCNT determines its many physical and chemical properties. The C=C covalent bond constituting the carbon nanotube is the most stable chemical bond in nature, so that the carbon nanotube has very excellent mechanical properties. Theoretical calculations show that MCNT have extremely high strength and great toughness. Moreover, MCNT have a large specific surface area and pore volume, which is beneficial for drug loading. MCNT have been successfully used as carriers for various drugs. Although there were many reports on the application of Multi-walled carbon nanotubes in slow-controlled release systems, pH sensitive systems and functionalized systems, it was rarely applied to the colonic targeted delivery system. Also, these applications also demonstrated that Multi-walled carbon nanotubes had the potential and was suited for condition of the colonic targeted delivery system.

In our study, the Multi-walled carbon nanotubes were applied to the colonic targeted delivery system to solve practical clinical application problems. We have prepared enzymatic-sensitive pectin capped MCNT as colon-specific drug delivery using self-assembly method. The structure of the Pectin-MCNT was characterized by FT-IR, DSC and Raman techniques. To evalute the possibility of using Pectin-MCNT as colon-specific drug delivery system, the insoluble non-steroidal anti-inflammatory drugs, Celecoxib, was incorporated into MCNT. PM-tablet with about 12 mm in diameter was successfully prepared. The swell and degradation results showed that PM-tablet had a enzyme independent controlled drug release properties. The PM-tablet wasnot damaged in the gastrointestinal tract (pH 1.2, 6.8 and 7.4) and transport the drug to the colon. Moreover, the PM-tablet in presence of pectinase exhibited degradation release. It showed that they were degraded under the action of the enzyme and achieve a precise release in colon.

Experimental

Materials

Pectin (low-methoxyl) and pectinase were all purchased from Guoyao chemical reagent Co. Ltd. All the pectin was purified using the alcohol-precipitation procedure [33]. Sodium alginate, chitosan and calcium chloride were all purchased from Sigma–Aldrich (St. Louis, MO, USA). MCNT was obtained from Nanjing pioneer nano material technology Co. Ltd. Indomethacin (purity > 99.0%) was purchased from Wuhan yuan cheng gong chuang technology Co. Ltd. All other chemicals were used in accordance with the requirements of analytical/spectroscopic/HPLC grade. Deionized water in all experiments was prepared by ion exchange.

Preparation of the tablets

Synthesis of the MCNT-CEL

CEL was incorporated into MCNT by a solvent deposition method [34]. CEL was dissolved in methanol to obtain a homogeneous solution (10 mg/mL), and then the solution was ultrasonicated for 20 min to ensure that CEL was completely dissolved. MCNT was added into the above solution at a certain proportion (1:1) to get a mixture. Subsequently, the obtained mixture was stirred for 24 h at room temperature in a closed container until the adsorption equilibrium was completed. Finally, the solvent was evaporated in the air under gently stirring and then the precipitated powder was dried at 45 °C in the oven until no organic solvent residue. The samples were labeled IMT (Abbreviations for CEL-MCNT).

Preparation of pectin-MCNT-CEL tablet

MCNT colonial tablets with pectin contents were prepared by wet granulation method. The main compositions of formulations were MCNT-CEL, pectin and calcium chloride. The MCNT-CEL, pectin and calcium chloride were accurately weighted and mixed with 10% w/v PVP solution to prepare soft materials. Subsequently, the above mixture was granulated through a 16 mesh sieve and dried at 45 °C in the drying oven, and then they were blended with moderate magnesium stearate (0.5% w/w) to form the granules for preparation of tablets. At last the granules were compressed to form tablets using a tableting machine.

Characterization techniques

Physical evaluation of the PM-tablet

Prepared tablets were evaluated for hardness, thickness, friability. A vernier caliper was used to measure the thicknesses of tablets and mean thicknesses of 20 randomly tablets was calculated. The hardness and the brittle broken degrees was both determined by the tablet tester with four functions. (tianjin xinzhou technology co., LTD.). Ten tablets were pressed to study the hardness and tablets (weighing 6.5 g) were made free-fall movement for 4 min at 25 rpm to monitor the weight loss of tablets. All results were showed as the mean ± standard deviation (SD).

TEM and photograph analysis

The surface morphology of the samples was photographed by a camera (Sony, RX-100, Japan). The TEM (CSIS EM-208S, USA) was used to investigate the internal structure of the samples. The samples were fixed on the copper network to be characterized.

FT-IR analysis

FT-IR spectrometer (Thermo Nicolet 380, USA). was used to characterize the functional groups and chemical bonding of samples. The samples were characterized in the scanning range of 400–4000 cm−1.

DSC analysis

The crystalline characteristics of the samples were measured by a DSC instrument (HCR-1, Hengjiu, China). The temperature range was 50–200 °C at a heating rate of 10 °C/min.

Optimized prescriptions using the star design and response surface method

In order to optimize the excellent formulation and prepare the tablets with acceptable hardness and friability, the star design and response surface method was used to guide the completion of this experiment. Based on the single-factor study, the proportion of pectin, MCNT and pregelatinized starch in the excipients had a great influence on the properties of the tablets. According to the results of the preliminary investigation, the amounts of pectin (X1), MCNT (X2) and pregelatinized starch (X3) were the main factors for investigation. The range of each fraction was X1: 50–90%; X2: 20–100 mg; X3: 0–8%. According to the principle of star design, each factor was setted 3 levels, which was represent using available code values − 1, 0 and 1. For the 3-factor star design α = 1. 732. The proportional relationship between the code value and the actual the physical quantity was shown in Table 1.

Table 1 Levels of independent variables in codes and physical meaning
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Swelling study

A certain number of tablets were placed in different glass test beaker, which contained simulated gastric fluid (pH 1.2), simulated intestinal fluid (pH 6.8) or simulated intestinal fluid (pH 7.4), respectively. The tablets were allowed to swell in simulated gastric fluid (pH 1.2) for 2 h at 37 °C,and then the tablets were washed with a little water and removed to swell in simulated intestinal fluid (pH 6.8) for 4 h at 37 °C. After that, the tablets were still washed with a little water and removed to swell in simulated intestinal fluid (pH 7.4) for 4 h at 37 °C. The designed swelling process was completed. Subsequently, the tablets were all taken out periodically and put on a filter paper to remove excess water. The weight changes of tablets were measured when it reached a mass equilibrium.

The swelling degree (% SD) is calculated using the following equation:

$${\text{SD}}\% = W_{\text{t}} - W_{\text{o}} \, /W_{\text{o}} \times 100\%$$

where Wt was the weight of the tablets at a certain time point and Wo was the initial weight of the tablets.

Enzyme degradation study

On the basis of the swelling experiment, the tablets were placed in simulated gastric fluid (pH 1.2) for 2 h and in simulated intestinal fluid (pH 6.8) for 4 h. The swelling process of was completed. The tablets treated with the swelling were placed in simulated intestinal fluid (pH 7.4), which contained the pectin enzyme. The state and completeness of the tablets should be observed at intervals. The weight changes of tablets were also measured.

The degradation degree (% DD) is calculated using the following equation:

$${\text{SD}}\% = W_{\text{o}} - W_{\text{t}} \, /W_{\text{o}} \times 100\%$$

where Wt was the weight of the tablets at a certain time point and Wo was the initial weight of the tablets.

In vitro release profile study

Dissolution studies were carried out using a USP II paddle method with a dissolution instrument (RCZ-8B, Shanghai Huanghai Test Instrument Co. Ltd.). The dissolution media was artificial gastric fluid (pH1.2), phosphate buffer (pH 6.8) and phosphate buffer (pH 7.4) with 2.0 g/L pectinase, respectively. The dissolution process was divided into three phases. The tablets were added in artificial gastric fluid (pH 1.2) and kept for 2 h. Subsequently, The tablets were removed in the phosphate buffer (pH 6.8) for 4 h. At last, The tablets were removed in the phosphate buffer (pH 7.4) with pectinase and kept for 4 h. The stirring rate was setted at 100 rpm. 5 mL samples were taken out at designated intervals (1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 h). The amount of CEL dissolved was determined by spectroscopy (UV-T6, General Analysis Beijing General Instrument Co., Ltd.) at 254 nm (n = 6).

Results and discussion

Synthesis and characterization of MCNT and Pectin-MCNT tablets

MCNT, pectin, drugs and other ingredients were pressed into tablets using wet granulation tabletting method. Tablets pressed directly with pectin were white (Fig. 1d). In contrast, when MCNT, pectin and other ingredients were grouped into tablets, the tablets showed a black color (Fig. 1c). It showed that the MCNT were distributed in the tablet system. The above results illustrated the MCNT successfully embedded in the pectin.

Fig. 1
figure 1

SEM of MCNT (a), TEM of MCNT (b, f) and MCNT-CEL (e), Photograph of PM-tablets (c) and PM-tablets without MCNT (d)

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In order to further analyze the components inside the tablet, TEM were utilized to complete this test. To prepare PM-tablet, MCNT-CEL was firstly synthesized using solvent evaporation method, which was an useful method for loading drugs into MCNT. The TEM results showed that the MCNT had a narrow tube structure, which was conducive to drug store inside the pipeline and improve the drug loading (Fig. 1a). In order to clearly see the pore structure of MCNT, it was studied by the TEM. We can clearly see the hollow tubular structure of the MCNT. The long tubular structure of MCNT was clearly visible and mutually entangled with each other (Fig. 1b, f). As saw in the Fig. 1e, in contrast to unload MCNT, there were some particles in the channels of MCNT. This further illustrated that the drug had been filled into the interior of the MCNT. This further proved that the pectin in the tablet had a perfect package for the drug.

The FI-IR analysis

The inclusion of CEL into the MCNT was confirmed by FI-IR. The FT-IR spectrum of samples (MCNT, CEL, MCNT-CEL) were presented in Fig. S1. The MCNT showed the wide adsorption bands in the range of 3600–3300 cm−1 due to the properties of carbonized materials. A sharp double peak at 3428 cm−1 and 3278 cm−1 for CEL was evidently showed. Furthermore, two single peaks were also shown at 1348 and 1164 cm−1. These characteristic peaks all belonged to the amino groups and sulfonyl groups in CEL, respectively. However, all the amino peaks were not showed in the spectrum of the MCNT-CEL, which may be due to covalent bonding between the CEL and the MCNT. The above results showed that the drug had been filled into the MCNT. For pectin, a strong and wide absorption peak appeared at 3814 cm−1 and 2993 cm−1, which was correspond to the carboxyl groups of pectin (Fig. S2). PM-tablet had a wide and flat absorption peak appeared from 3050 cm−1 and 3637 cm−1 (Fig. S2), which cannot clearly determine its assigned functional groups. So functional groups for the MCNT-CEL cannot clearly show its characteristics, which may be due to their complex composition for the tablets. These results showed that PM-tablet was successfully prepared. The FI-IR spectra of PM-tablet containing pectin at 50%, 60%, 70%, 80% and 90% was further carried out to study the effect of pectin on the structure of PM-tablet (Fig. 2). The Pectin50-MCNT-tablet showed a sharp peak at around 1635 cm−1 and the wide adsorption bands in the range of 3000–3700 cm−1. The PM-tablet with 50%, 60%, 70%, 80% or 90% of pectin all showed the almost same characteristic peaks. This showed that the content of pectin had no obvious effect on the structure.

Fig. 2
figure 2

FTIR spectra of Pectin-MCNT-tablet with different amounts of pectin (50%, 60%, 70%, 80%, 90%)

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The DSC analysis of PM-tablet and its associated components

The crystalline characteristics of MCNT, CEL, MCNT-CEL, pectin, CaCl2 and their formulations were further studied using DSC. As we all know, the characteristic peak of the pure drug at the melting point can be detected in the DSC curves. However, if the drug was in an amorphous state, the absorption peak will not appear on the DSC profiles. As shown in Fig. 3, pure CEL showed a sharp characteristic peak at around 164.7 °C, which was consistent with its melting point. In contrast, there were not any characteristic peak in the profiles of MCNT and pectin. Moreover, the characteristic peaks of CEL in MCNT-CEL were weakened, which indicated that CEL had been incorporated into the channels of MCNT. In addition, the CaCl2 showed a sharp characteristic peak at around 158.4 °C and the double characteristic peaks at about 210.3 °C and 220.7 °C. Surprisingly, the characteristic peaks of the drug were covered by the PM-tablet. This may be due to that the characteristic peaks of the various components in the PM-tablet overlapped each other. So it was also difficult to tell if the drug’s crystalline form was affected. It was observed that the absorption intensity of the PM-tablet was increased when increasing the pectin ratio in the PM-tablet (Fig. S3).

Fig. 3
figure 3

DSC patterns of MCNT, CEl, MCNT-CEL, pectin, CaCl2 and PM-MCNT

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Prescription optimization study

The relationship between the various factors and response values was evaluated by studying the three-dimensional response surface plots, which were used to optimize tablet prescriptions. Figure 4 showed the effect of pectin and pregelatinized starch on hardness. The amounts of pregelatinized starch were found to have a significant effect on the hardness of the formulation in comparison to the amount of pectin. Increase in the amount of starch paste led to an increase the hardness of the formulation. This may be due to that pregelatinized starch in the concentration of 5–40% in tablet granulation acts as a binder. Figure 4 showed the effect of pectin on hardness. No evident effect was seen on changing the level of pectin (50–90%) on the hardness of the formulation. This may be explained by the nature of the pectin itself. Pectin was a type of macromolecule polysaccharide. The structure was dominated by linear polysaccharides, which contain chain structures formed from several hundred to over one thousand glycogen [35]. So it can not make too much contribution to the hardness of the tablet. The effect of MCNT on hardness was showed in Fig. 4. Although MCNT had a rigid structure, MCNT embedded in the framework of calcium pectin did not have a significant effect on the hardness of the PM-tablet. However, different results appeared in the experimental results of the friability. Increase in the amount of MCNT resulted to an increase the friability of the formulation. It showed that MCNT can increase the fragility of the PM-tablet. Based on the impact of the above factors on tablets, the optimized tablet prescription was determined combination with the response surface consequences analysis. Each effect surface had its own optimal region, which can be superposed to further narrow the scope of the optimal region. Therefore, we superimpose the contour map corresponding to the effect surface to obtain optimized area. The optimal formulation for tablets was finally determined as: X1 = 70%, X2 = 60 mg, X3 = 22.5%.

Fig. 4
figure 4

Response surface plots showing effect of pectin, MCNT and pregelatinized starch on Hardness (N) and Friability (%)

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Swelling study

PM-tablet as a carrier was used to deliver MCNT-drugs to the colon. Swelling behavior of PM-tablet determined the release process and the degradation of them to a great extent. In order to evaluate that the PM-tablet could withstand the various pH conditions of the gastrointestinal tract, swelling studies were used to measure the integrity of the PM-tablet in the simulated gastrointestinal tract. As shown in Fig. S4, the diameter of the Pectin50-MCNT-tablet increased from 11.01 mm to 17.2 mm after 10 h swelling test. Moreover, the diameter of the Pectin90-MCNT-tablet increased from 11.01 mm to 18.3 mm after 10 h swelling test. The increase in diameter did not destroy this structure of the PM-tablet. It can be seen that the PM-tablet still maintained its excellent integrity in the whole swelling process (Fig. S4). The stable structure proved that they were difficult to be destroyed in the gastrointestinal tract without pectinase. Moreover, it was surprised that there was no leakage phenomenon for the MCNT in the medium. This may be due to that pectin calcium cross linked by the pectin and calcium chloride had a solid “Egg-shell” structure, which was difficult to be damaged by the gastrointestinal environments. Pectin calcium was a rigid gel and its structure was especially stable. It was only biodegradable in the presence of pectinase. And it had a three-dimensional network structure, which effectively encapsulated carbon nanotubes in it. So pectin calcium in the medium (pH 1.2, pH 6.8 and pH 7.4) was not influenced by numerous pH medium and maintained its complete structure, which can effectively prevent the leakage of MCNT. It was also ensured that drugs were taken to the colon without any obstruction.

It can be observed in Figs. 5 and 6, the swelling degree was affected by the concentration of pectin. Pectin90-MCNT-tablet showed a higher swelling degree than that of the other tablets in various pH medium. The swelling degree of the Pectin90-MCNT-tablet reached 336% after 10 h swelling process, which had the largest change in diameter. It also indicated that the swelling degree increased with increasing pectin concentration. It can be due to that the water in the swelled tablets was absorbed by the pectin. So the amount of water bound was determined by the amount of pectin. In addition, the swelling rate of the PM-tablet exhibited irregular changes in the different pH media. The swelling rate of PM-tablet in the first 2 h was considered to be altered greatly, when they were placed in a simulated gastric fluid medium (pH 1.2). This indicated that pectin in the tablets rapidly absorbed the water in the medium (Fig. 6). The swelling rate began to slow down after 2 h absorption, when the water reaches certain saturation. The swelling degree of PM-tablet in 3–6 h was considered to be enhanced slightly and the swelling rate was close to the platform stage (Fig. 5). The results of Fig. 6 also supported this point. This may be explained by the following reasons. The water absorbed by the PM-tablet in the first 2 h was from the acidic medium (pH 1.2). But the pH gradient was formed owing to the different pH conditions inside and outside of the PM-tablet, when they were removed from the acidic medium (pH 1.2) to the alkaline medium (pH 6.8). And then the pH gradient between the inside and outside of the PM-tablet formed. Subsequently, the PM-tablet absorbed some water from the alkaline medium. Although the rate of increase in swelling was affected by the pH gradient, the degree of swelling continued to grow. All of these analyzes supported the point that PM-tablet retained their integrity under the influence of altered pH environments.

Fig. 5
figure 5

Swelling degree of Pectin-MCNT-Tablet with different amounts of pectin in the simulated conditions of gastrointestinal tract (pH 1.2, pH 6.8 and pH 7.4)

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Fig. 6
figure 6

Swelling behaviour of Pectin-MCNT-Tablet with different amounts of pectin in the simulated conditions of gastrointestinal tract (pH 1.2, pH 6.8 and pH 7.4)

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Enzyme degradation study

Degradation was a major character, which determined the drug release behavior of the PM-tablet. In order to evaluate that the PM-tablet could degrade in the colon with the enzyme environment, the PM-tablet was placed in the simulated conditions of stomach (pH 1.2) for 2 h and intestine (pH 6.8) for 4 h firstly. Subsequently, they were removed into the medium (pH 7.4) in the presence of pectinase to confirm that they accurately degraded in the colon. The results showed that a significant degradation of PM-tablet with different amounts of pectin appeared under the pectinase condition (Fig. S5A). This showed that PM-tablet had the ideal enzyme response properties. It was further showed that the degradation behavior of PM-tablet was significantly affected by the amounts of pectin. In pH 7.4 medium with pectinase, the degradation degree of PM-tablet with 90% pectin was found to be higher than that of PM-tablet with 50% pectin. Moreover, the stable degradation equilibrium was completed more rapidly in PM-tablet with 90% pectin than in PM-tablet with 50% pectin. Increased degradation degree of PM-tablet may be due to that the amount of pectin determined the extent to which the tablet destroyed after enzymatic degradation. After 90% pectin was degraded by pectinase, the remaining 10% of the composition were hard to support the structure of the whole tablet, so the PM-tablet with 90% pectin was broken down to a greater extent. In contrast, when 50% pectin of tablets were degraded, their integrity had remained higher than that of 90% of pectin tablets. In addition, the degradation of PM-tablet was not substantially affected by the amounts of the MCNT. As the amount of MCNT increased, the degradation of PM-tablet with different amounts of the MCNT did not show a significant difference (Fig. S5B). This may be due to the fact that MCNT with the rigid structure did not bind with pectin, which was also consistent with the FI-IR result. It noted that MCNT has no direct effect on the degradation of PM-tablet. The degree of pectin degradation determined the structure of the PM-tablet and the route of drug release. Therefore, the amounts of pectin played a decisive role for the degradation behavior of the PM-tablet.

In vitro release profile study

In order to evaluate the possible effect of pectinase on the release of PM-tablet in the simulated colonic environment, the in vitro release of CEL from the PM-tablet containing pectin at 50%, 60%, 70%, 80% and 90% were carried out in pH 1.2, 6.8 and 7.4 buffer solutions at 37 °C. Figure 7 showed that the swelling behavior of pectin had a significantly effect on the drug release curves. In the first 6 h, as the amount of pectin increased, the accumulated release amounts of drug released gradually also increased. This can be explained in that the rate of swelling of pectin increased when amount of pectin enhanced. It had been reported that pectin could form a saturated swelling gel by absorbing water, which was the medium for drug dissolution [36]. Rapid absorption of water provided a pathway for drug diffusion. So the rate of drug release from the tablets also increased with the increase of the amount of pectin. However, the accumulated release amounts of drug released from the PM-tablet with different amounts of pectin was all less than 30% within the first 6 h. This may be due to the fact that the drug was inside the MCNT with a rigid structure and the MCNT had an undesirable fluidity in a pectin-based tablet. So that the drug released from the MCNT cannot smoothly diffuse out of the swelling tablets. This was likewise the reason for that pectin and MCNT were combined to make tablets. It could had control over the release of drugs and targeted specifically to the colon without rapid premature release. This was further confirmed by the swelling tests. The PM-tablet achieved an increase in diameter from 1 to 5 in the gastrointestinal tract simulation environment and maintained their integrity.

Fig. 7
figure 7

Dissolution profiles of Pectin-MCNT-Tablet with different amounts of pectin (50%, 60%, 70%, 80% and 90%)

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After release in no enzyme environment, the PM-tablet was enclosed in medium with enzyme environment. The results showed that the PM-tablet in presence of pectinase exhibited degradation release compared to PM-tablet without pectinase. PM-tablet showed a faster release at 7 h, which may be attributed to the presence of pectinase which degrade pectin and thus accelerate drug release. Moreover, the release behavior of CEL was mainly affected by the amounts of the pectin. The accumulative release amounts of CEL increased on increasing the amounts of the pectin. This could be explained by that the higher the pectin content, the more severe structural damage of the tablet after enzymatic hydrolysis. Drugs moved more easily into the dissolution medium. For example, accumulated release amounts of drug released from Pectin90-MCNT-Drug-Tablet were much faster than that of Pectin50-MCNT-Tablet in 7 h. This was also confirmed by the degradation tests. The degradation degree of Pectin90-MCNT-Drug-Tablet was significantly higher than that of Pectin50-MCNT-Tablet in the environment containing pectinase. This also showed that pectin played a major role in the integrity of the tablets and drug release. It further reported that the PM-tabletachieved the purpose of transporting the drug to the colon site and then releasing the drug under the degradation of the pectinase. The PM-tablet showed an enzyme independently controlled drug release behavior.

Conclusion

The PM-tablet was successfully develoted and characterized. The characterized results showed that the drug had been filled into the interior of the MCNT and the MCNT successfully embedded in the pectin. The swelling study indicated that the PM-tablet could withstand the various pH conditions of the gastrointestinal tract and effectively prevent the leakage of MCNT. Moreover, the swelling degree increased with increasing pectin concentration, which may be explained by that the amount of water bound was determined by the amount of pectin. Enzyme degradation study showed that the PM-tablet had an enzyme independently controlled drug release behavior. In addition, the degradation behavior of PM-tablet was also adversely affected by the amounts of pectin. At last, the vitro dissolution results showed that the accumulative release of the PM-tablet with different amounts of pectin was well less than 30% for 6 h in no enzyme environment. However, the PM-tablet in presence of pectinase exhibited degradation release compared to PM-tablet without pectinase. The PM-tablet achieved the purpose of carrying the drug to the colon site and then releasing the drug under the degradation of the pectinase. The PM-tablet showed an enzyme independently controlled drug release behavior. The enzyme depended drug release tendency of MCNT could be useful especially for its exploitation as colon specific drug delivery system.