Crosslinked γ-cyclodextrin metal organic framework for stable ibuprofen loading

Ibuprofen (IBU) is a commonly used non-steroidal anti-inflammatory drug (NSAIDs), but its solubility is poor in both aqueous and physiological environments . To improve its oral bioavailability and absorption, IBU is loaded into a material, with cyclodextrin metal–organic frameworks (CD-MOFs) being a promising drug carrier. To overcome the instability of CD-MOFs in humid conditions, a cross-linking agent Isophorone diisocyanate (IPDI) was introduced, and a novel cross-linked material CL-CD-MOFs was prepared. On this basis, two IBU-loaded materials, CL-CD-MOFs-IBU, were prepared through different reaction sequences. Research shows that CL-CD-MOFs exhibit stability in water and humid environments, whereas CD-MOFs readily dissolve. Furthermore, this material demonstrates higher IBU loading and encapsulation rates, as well as sustained drug release. Cell toxicity studies indicate that CL-CD-MOFs-IBU exhibit good biocompatibility.


Introduction
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID) with low systemic toxicity in clinical practice.It is commonly used for its anti-inflammatory, analgesic, antipyretic, and anti-rheumatic properties.Compared to other NSAIDs such as aspirin and indomethacin, ibuprofen carries a relatively lower risk of causing gastric damage as a side effect [1].Ibuprofen is also utilized in the treatment of chronic inflammation, degenerative diseases, and various types of cancer [2][3][4].Some studies have even indicated that ibuprofen can extend the lifespan of yeast, worms, and flies [5].However, due to its short half-life (only 1.5-2h), ibuprofen reaches its peak plasma concentration within 1-2h after administration, making it challenging for the human body to effectively absorb and utilize [6].Loading ibuprofen onto a polymer material can increase its half-life in vivo and maintain the stable blood drug concentration, providing a certain sustained-release effect.Therefore, selecting suitable high molecular materials as carriers is an effective approach to improve the pharmacokinetic characteristics of the drug [7][8][9].
Metal-organic frameworks (MOFs) are organic-inorganic hybrid porous crystalline materials assembled by metal ions or clusters with organic ligands through coordination bonds [10][11][12].MOFs possess excellent characteristics such as high surface area, high porosity, tunable structure-functionality, and strong encapsulation ability for guest molecules, making them promising for drug delivery applications [10][11][12][13][14].However, traditional MOF materials exhibit significant biotoxicity, which limits their application in the field of biomedicine.Therefore, in recent years, numerous researchers have been devoted to reducing the cytotoxicity of MOFs materials to improve their biocompatibility for better application in biomedicine.
Cyclodextrin (CD) is a cyclic carbohydrate formed through the degradation of amylase.Due to its high biocompatibility, CD has received extensive attention in the preparation of MOFs materials [15].CD has a unique three-dimensional cone-shaped cavity structure with hydrophobic interior and hydrophilic exterior.When combined with potassium ions, it forms Cyclodextrin Metal-Organic Frameworks (CD-MOFs), which exhibit large surface area, high porosity, good biocompatibility, and high drug-loading capacity [16,17].Moreover, compared to other carriers, CD-MOFs have the advantages of readily available and cost-effective starting materials, making them highly promising for applications in the field of biomedicine [18][19][20][21].Current research indicates that CD-MOFs have significant advantages in improving solubility, enhancing bioavailability, and reducing adverse reactions when loaded with drugs such as omeprazole [22], diflunisal [23], budesonide [24], and ibuprofen [25].For example, Karel et al synthesized CD-MOFs based on the γ-cyclodextrin (γ-CD) toroidal surface and loaded ibuprofen, resulting in a 100% extension of its half-life in plasma samples [25].However, CD-MOFs have drawbacks such as the instability of their cubic structure in water and the tendency to disintegrate in humid environments, leading to premature drug release and the sustained release effect difficult to maintain [26].
To improve the stability of CD-MOFs in water environments, researchers have explored surface modifications and physical loading approaches.For instance, Singh et al [27] enhanced the water stability of CD-MOFs by surface modification with cholesterol.However, the hydrophobic layer was susceptible to penetration and disruption by water molecules, leading to structural collapse.Li et al [28] introduced fullerene (C60) into CD-MOFs to increase their water stability, but the improvement on the stability of CD-MOFs was limited, and the occupancy of the hydrophobic cavity of γ-CD by C60 could reduce the drug-loading capacity of CD-MOFs.Cross-linked CD-MOFs prepared by utilizing the hydroxyl groups on CD-MOFs for further modification and functionalization offer several advantages.They not only remove metal ions, avoiding adverse reactions caused by high concentrations of metal ions in biological systems and enhancing biocompatibility, but also retain the inherent advantages of the original morphology, thereby improving the stability of CD-MOFs in aqueous solutions.For instance, Singh et al [29] employed diphenyl carbonate as a cross-linker and triethylamine (TEA) as a catalyst to chemically cross-link the carbonate ester bonds with the hydroxyl groups on CD-MOFs.This resulted in the preparation of cross-linked cyclodextrin metal-organic frameworks with nano-and micro-sized cubic structures.The method not only enhanced the stability of CD-MOFs in water but also shortened the reaction time without affecting their cubic structure.
In this study, a novel cross-linked CD-MOFs material was prepared based on the presence of modifiable and functionalizable hydroxyl groups on the CD-MOFs structure.Isophorone diisocyanate (IPDI) was used as a cross-linking agent, and the solvent diffusion method was employed to fabricate the cross-linked CD-MOFs.The advantage of IPDI was the ability to react with water, allowing the residual crosslinker after the synthesis reaction to react with water and be removed as small molecules, facilitating the purification of the final product.In this study, the cross-linking interaction was employed to load ibuprofen, enhancing the stability of CD-MOFs in water, delaying drug release, and simultaneously improving the drug encapsulation rate and drug loading capacity.

Preparation of CD-MOFs
163 mg of γ-CD was dissolved in 5 ml of KOH aqueous solution.The solution was then filtered through a 13 mm syringe filter with a 0.45 μm polytetrafluoroethylene (PTFE) membrane into another beaker.The beaker was placed in a closed container containing 5 ml of methanol to allow for evaporation and diffusion of methanol into the solution.The reaction was carried out at 50 °C for 6h.Afterward, 5 ml of the reaction solution was taken and mixed with 40 mg of cetyltrimethylammonium bromide (CTAB) and 5 ml of methanol.The mixture was stirred until dissolved and left to stand overnight.Finally, the obtained solution was centrifuged at 4000 rpm for three minutes to remove the supernatant.The resulting CD-MOFs were washed several times with N,Ndimethylformamide.
2.3.Preparation of CL-CD-MOFs 0.25 g of the synthesized CD-MOFs from step 2.2 were dissolved in a suitable amount of DMF solvent.Then, 0.1382 g of the crosslinking agent isophorone diisocyanate was added, and the reaction was carried out at 70 °C for 4 h.The solution after the reaction was centrifuged at 4000 rpm for three minutes to remove the supernatant.The remaining solid was washed with DMF several times and dried overnight under vacuum at 60 °C, resulting in CL-CD-MOFs.
2.4.Preparation of CL-CD-MOFs-IBU-1 163 mg of γ-CD and 26 mg of ibuprofen were dissolved in 5 ml KOH aqueous solution and then filtered using a 13 mm syringe filter with a 0.45 μm PTFE filter membrane into a separate beaker.The beaker was then placed in a sealed container containing 5 ml of methanol, and the methanol was allowed to evaporate and diffuse into the solution for 6 h at 50 °C.5ml of the solution after the reaction was mixed with 40 mg of cetyltrimethylammonium bromide and 5 ml of methanol, stirred and left overnight.The obtained solution was centrifuged (4000 rpm) for three minutes to remove the supernatant, and CD-MOFs-IBU were obtained after being washed with DMF several times.0.25 g of synthesized CD-MOFs-IBU was dissolved in a suitable amount of DMF solvent and 0.1382 g of IPDI was added, and the reaction was carried out at 70 °C for 4 h.The solution after the reaction was centrifuged at 4000 rpm for three minutes to remove the supernatant.The remaining solid was washed with DMF several times and dried overnight under vacuum at 60 °C, resulting in CL-CD-MOFs-IBU-1.

Preparation of CL-CD-MOFs-IBU-2
0.25 g of CD-MOFs synthesized in step 2.2 was taken and dissolved in an appropriate amount of DMF solvent.Then, 0.1382 g of the cross-linking agent, IPDI, was added and the mixture was reacted at 70 °C for 4 h.Afterwards, 26 mg of ibuprofen was added to the reaction solution, stirred for 2 h, and centrifuged at 4000 rpm for three minutes.Finally, the obtained precipitate was washed three times with methanol, dried overnight under vacuum at 60 °C, and CL-CD-MOFs-IBU-2 was obtained.

Characterization
The KBr disk-shaped samples containing 1 wt% of material were prepared using KBr press technique.The Fourier transform infrared spectroscopy (FTIR) spectra of each sample were recorded using Thermo Nicolet IN10 infrared spectrometer in the range of 400-4000 cm −1 with a resolution of 4 cm −1 and an average of 64 scans.The surface morphology of the samples was observed using a scanning electron microscope (SEM) (ZEISS Sigma 300) at an acceleration voltage of 10.0 kV.The particle morphology of the prepared samples was observed using FEL Tecnai G2 F30 field emission transmission electron microscopy (TEM) at an acceleration voltage of 80 KV.The powder sample was tested for x-ray diffraction (XRD) using Ultima IV diffractometer.The crystallization of dried CD-MOFs was placed on a carrier slide, and the scanning speed was set to 10°/min for the testing at 10°−80°2θ angle range using a diffractometer.Dynamic light scattering (DLS) of polymer nanoparticles was performed on Malvern Zetasizer nano-zs90 instrument at room temperature.The thermogravimetric analysis (TGA) curve of the sample was determined using a TG Q50 thermogravimetric analyzer by placing 20-30 mg of the sample in an aluminum crucible, setting the temperature range to 30 °C-800 °C, increasing the temperature at a rate of 10 °C min −1 , and using 20 ml min −1 of N 2 flow rate.A 1 mg•mL −1 suspension of the sample was prepared, and its ZETA potential was measured using dynamic light scattering on a Malvern ZETAsizer Nano ZS90.The water static contact angle of the sample was measured at room temperature using a JY-82 contact angle measuring instrument (Germany).The sample was placed in a test tube with 100mg and then 7 ml of deionized water was added to the test tube, shaken for 1 min, and the state of the sample was observed to evaluate its water stability.To test the moisture resistance of the samples, they were placed in plastic culture dishes and observed for 8 h in a high humidity environment.The N 2 adsorption performance of the sample was measured using the Micromeritics ASAP2460 instrument.100-200 mg of washed sample was dried overnight under vacuum, and then the sample was treated with degassing at a temperature of 50 °C for 4-5 h, followed by testing the sample for N 2 adsorption performance at liquid nitrogen temperature (77 K, −196 °C).
The encapsulation rate and drug loading of the sample were measured through UV-vis spectroscopy.Firstly, IBU solutions with concentrations of 1 mg ml −1 , 2 mg ml −1 , 4 mg ml −1 , and 8 mg ml −1 were prepared, and the absorbance was measured at a wavelength of 265 nm using a UV-vis spectrophotometer to obtain a standard curve.To evaluate the encapsulation rate and drug loading of the sample, a 10 mg ml −1 IBU solution was prepared, and an appropriate amount of the sample was dissolved in the IBU solution, stirred at room temperature with a magnetic stirrer at 200 rpm for 1 h to mix well, and then allowed to stand for 10 min.The supernatant was collected and the absorbance was measured at a wavelength of 265 nm using a UV-vis spectrophotometer.Finally, the drug content in the sample was calculated based on the standard curve of IBU.
The formulas for calculating drug loading and encapsulation rate are as follows [30].Phosphate buffer (PBS) is prepared by adding 8 g NaCl, 0.2 g KCl, 0.24 g KH 2 PO 4 , and 1.44 g NaHPO 4 to 1000 ml of deionized water.The pH is then adjusted to 7.4.A dialysis bag method was used to determine the in vitro drug release characteristics of the sample, with the prepared PBS as the release medium.10 mg of the sample was weighed and added to a dialysis bag, then added to 100 ml of phosphate buffer solution (pH 7.4).It was placed in a constant temperature shaker at 37 °C, the speed was set to 50 rpm, and 5 ml was taken at 0 h, 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, and 12 h, with an equal volume of release medium added.The sample solution was taken, filtered through a 0.22 μm membrane, the absorbance at 265 nm was measured, and the cumulative release of IBU was calculated.
In vitro cytotoxicity of the sample was determined using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-htetrazolium bromide (MTT) assay.L929 cells were used in the experiment.Cultured L929 cells were seeded at a density of 1 × 10 4 per well in a 96-well plate, and 200 μl of dulbecco's modified eagle medium (DMEM) complete medium was added.The plate was placed in a 37 °C constant temperature incubator and cultured for 24 h until the cells completely adhered to the wall.Different samples with a concentration of 0.5 mg mL −1 were added to the culture plate, and a culture medium without a sample was set as the control group.Five parallel wells were set for each sample.After incubating for 24, 48, and 72 h, the culture medium was removed, 3-(4,5dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide MTT solution was added, and the plate was further incubated for 4h.The MTT was then discarded, and the plate was shaken for 15 min to dissolve the crystals.Finally, the optical density (OD) value of each well was measured using an ELISA reader, and the cell survival rate (%) was calculated.

Results and discussion
FTIR was used to analyze CD-MOFs, CL-CD-MOFs, CL-CD-MOFs-IBU-1, and CL-CD-MOFs-IBU-2 for identifying functional groups and their chemical compositions, as shown in figure 1.In the CD-MOFs spectrum, the characteristic peak at 3430 cm −1 represents the stretching vibration of -OH in γ-CD, while the peak at 2930 cm −1 is the stretching vibration of C-H in -CH3 and -CH2.The peak at 1028 cm −1 is the characteristic vibration of C-O-C, and the peak at 1650 cm −1 is the vibration of adsorbed water [30,31].Compared with CD-MOFs, a characteristic peak of N-H stretching vibration at 1558 cm −1 appears in the CL-CD-MOFs spectrum, indicating that the isocyanate group in IPDI has successfully reacted with the hydroxyl group in γ-CD, and the crosslinking agent has been successfully introduced.The peak at 1700 cm −1 is the -COOH group in IBU.Moreover, the peak of CL-CD-MOFs-IBU-1 is stronger than that of CL-CD-MOFs-IBU-2, which may be because IBU was added first during the synthesis of CL-CD-MOFs-IBU-1.Thus, more hydrogen bonds were formed between the carboxyl groups in IBU and the hydroxyl groups in the carrier material, and IBU was more easily retained.In contrast, the addition of IPDI to produce a crosslinking reaction in CL-CD-MOFs-IBU-2 resulted in spatial hindrance on the surface of CL-CD-MOFs and prevented subsequent addition of IBU to participate in the reaction in the material, leading to a decreased loading of IBU.
Further analysis of the structure of CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 was carried out through x-ray diffraction (XRD), as shown in figure 2. The XRD patterns of the two samples loaded with IBU were very similar, with narrow and sharp diffraction peaks, indicating a high degree of crystallinity of the samples.The peak positions of the two methods were basically the same, suggesting that the two synthesis methods did not cause any change in the overall structure of the material.
The surface morphology of CD-MOFs, CL-CD-MOFs, CL-CD-MOFs-IBU-1, and CL-CD-MOFs-IBU-2 were characterized by scanning electron microscopy (SEM), and the results were shown in figure 3. Figures 3(a) and (b) showed that CD-MOFs and CL-CD-MOFs have similar cubic structures and roughly the same particle size, indicating that the IPDI cross-linking does not affect the overall size of CD-MOFs [27].However, the pore size on the surface of CL-CD-MOFs became smaller due to the cross-linking of IPDI.This was mainly because the addition of the cross-linking agent IPDI can replace the potassium ions and hydroxyl groups of γ-CD to undergo cross-linking reaction, which changes the surface and reduces the pore size due to cross-linking, making it denser and more resistant to water molecules.The DLS curve (figure S1) demonstrates that the z-average diameter of CL-CD-MOFs is 492.2 nm, which is consistent with the SEM test results.No test data is available for CD-MOF dissolved in water.Contact angle measurement is an important method to characterize the surface wettability of materials [32].The contact angle of hydrophilic materials is below 90 degrees, while that of hydrophobic materials is between 90 and 150 degrees.As shown in figure 4, the contact angle of CD-MOFs was 55 degrees, showing hydrophilic properties, while the contact angle of cross-linked CL-CD-MOFs was 101 degrees, showing hydrophobic properties.When water droplets came into contact with the surface of CL-CD-MOFs, the ability of wetting decreased due to the difficulty of infiltrating the surface space structure of the cross-linking material by water molecules, resulting in an increase in the contact angle of the material surface.Static contact angle testing of water showed that the surface structure of CD-MOFs has been transformed from hydrophilic to hydrophobic through cross-linking.
The CD-MOFs and CL-CD-MOFs samples were added to water to test their water stability, and the results were shown in figure 5.After the CD-MOFs particles were added to water, they gradually began to dissolve in the water.After 1 min of shaking, all the CD-MOFs particles were dissolved.In contrast, the CL-CD-MOFs floated on the surface of the water after being added to the water, and after 1 min of shaking, the particles of CL-CD-MOFs still remained floating on the water surface, showing a distinct white particle form, indicating good water stability of the CL-CD-MOFs.The weak coordination of the metal-organic ligands in the CD-MOFs makes it easy for the water molecules with strong nucleophilicity to destroy their structure.Water molecules can easily enter the interior of the material, causing the CD segments inside the CD-MOF material in contact with water to move, resulting in the collapse of the internal skeleton structure of the material, leading to the complete  The hygroscopicity(deliquescence) experiments were conducted on CD-MOFs and CL-CD-MOFs, and the results are shown in figures 6(a) and (b).CD-MOFs gradually dissolved in a high-humidity environment, while CL-CD-MOFs remained stable and presented as white powder in a humid environment.The test results further confirmed that the surface of CL-CD-MOFs, due to the dense cross-linking structure and the presence of spatial hindrance, can effectively isolate the contact between internal coordinating agents and water molecules, as well as the protective effect of IPDI cross-linking on CD chain segments, preventing chain movement from damaging the framework and ensuring the stable existence of the material in a humid environment.
Further tests and analyses were conducted on the specific surface area of CD-MOFs and CL-CD-MOFs.The nitrogen adsorption-desorption isotherms of the samples are shown in figure 7.Both materials exhibited typical type I adsorption behavior, with the adsorption isotherms rapidly increasing at P/Po = 0.0-0.2,indicating the existence of microporous structures.The BET model was used to calculate the specific surface area of CD-MOFsas 255.3 m2 g −1 and CL-CD-MOFs as 240.2 m2 g −1 , indicating a slight decrease in the specific surface area of the crosslinked material.This may be due to the crosslinking effect, which reduces the pores on the CL-CD-MOFs material, leading to a decrease in specific surface area.
The ZETA potentials of CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 materials in ethanol were measured using a ZETA potential analyzer, with the results shown in figure 8.The ZETA potential on the surface of CL-CD-MOFs-IBU-1 particles was 0.590 mV, while CL-CD-MOFs-IBU-2 particles showed a ZETA potential of −6 mV.This is likely due to steric hindrance on the surface of CL-CD-MOFs material, making it difficult for IBU to enter the interior of the material.Most of the IBU reacted on the surface of the material, with some residual IBU remaining after washing.The number of -COOH groups on the surface of the material increased, ultimately resulting in a negatively charged material.In contrast, IBU entered the interior of CL-CD-MOFs-IBU-1 and reacted inside, resulting in less residual surface IBU and a ZETA potential of 0.590 mV.
The loading and encapsulation efficiencies of CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 were tested, and the results are shown in table 1.The loading efficiency of CL-CD-MOFs-IBU-1 was 6.16 wt%, and the encapsulation efficiency was 84.62%.The loading efficiency of CL-CD-MOFs-IBU-2 was 4.76 wt%, and the encapsulation efficiency was 65.4%.The loading and encapsulation efficiencies of CL-CD-MOFs-IBU-1 were both higher than those of CL-CD-MOFs-IBU-2.This is mainly because IBU in pre-loaded CL-CD-MOFs-IBU-1 can participate in the reaction first, and form hydrogen bonds with the active hydroxyl groups on CD-MOFs, which effectively enhances the stability of the material and enables IBU to be more stably loaded onto CD-MOFs.In the subsequent synthesis, the surface of the material can form a grid structure after IPDI crosslinking, which not only enhances the stability of the material, but also effectively fixes IBU in CL-CD-MOFs.In contrast, when synthesizing CL-CD-MOFs-IBU-2, IPDI first participates in the reaction with CD-MOFs, and the isocyanate group in the IPDI structure reacts with the active hydroxyl groups in CD-MOFs to form a grid structure on the surface of the material, which increases the steric hindrance of the surface and makes it more difficult for the subsequently added IBU drug molecules to enter and participate in the reaction inside CD-MOFs, ultimately resulting in a decrease in the IBU content in the material.
Further testing and analysis of IBU in vitro release from CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 were conducted and the results are shown in figure 9.As seen from the figure, the drug release of CL-CD-MOFs-IBU-1 reached 15% at 1 h and 30% at 12 h, while the release of CL-CD-MOFs-IBU-2 reached 19% at 1 h and 38% at 12 h.The in vitro release experiment results showed that both materials have a sustained-release effect, and CL-CD-MOFs-IBU-1 exhibited a more persistent release ability than CL-CD-MOFs-IBU-2.This may be   due to IBU in CL-CD-MOFs-IBU-1 participating in the reaction first, reacting with active hydroxyl groups on CD-MOFs material to form hydrogen bonds, increasing the difficulty of IBU separation from the material and prolonging the release time of IBU from the carrier material.In CL-CD-MOFs-IBU-2, IPDI participated in the reaction with CD-MOFs first, where the isocyanate group in the IPDI structure reacted with the active hydroxyl group in CD-MOFs, resulting in a decrease in hydrogen bonds formed between IBU and CD-MOFs, reducing the stability of the CL-CD-MOFs-IBU-2 material and decreasing the difficulty of IBU release from the carrier material, and subsequently shortening the required release time.
The thermal stability of CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 was studied through TGA and the thermal degradation curves are shown in figure 10.The overall thermogravimetric curves of the two materials are roughly the same, divided into five stages of weight loss.The weight loss from 20 °C to 120 °C is due to the volatilization of adsorbed free water and solvent molecules in the material, while the weight loss from 120 °C to 170 °C is due to the thermal decomposition of IBU encapsulated in the material at high temperature.The weight loss from 170 °C to 245 °C is attributed to the loss of coordinated water molecules and hydroxyl groups.The weight loss rate is the fastest from 245 °C to 400 °C, which may be due to the thermal decomposition of γ-cyclodextrin and the collapse of the crystal structure under high temperature.The weight loss of the sample is slow from 400 °C to 555 °C, which may be related to the carbonization of the sample.IBU interacts with  γ-cyclodextrin through inclusion reaction, and γ-cyclodextrin acts as a wall material, protecting IBU from external environmental influences.Moreover, hydrogen bonds are formed between IBU and the carrier material during the reaction, which further enhances the stability of IBU in the material [33].
In order to study the cytotoxicity of the material, the MTT analysis method was used, and the results are shown in figure 11.Polyurethane (PU) was used as the control group, and the cell survival rates of the control group and ibuprofen were close to 100%, while the cell survival rates of CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 were 92.13%, 85.10%, and 77.13% at 24 h, 48 h, and 72 h, respectively, and 89.97%, 80.93% and 76.17%, respectively.Compared with the control group and ibuprofen, the cytotoxicity of the two samples is lower, and the cell survival rate is above 75%.Therefore, CL-CD-MOF loaded with IBU can be used as a safe drug delivery system.The cytotoxicity of CL-CD-MOFs-IBU-1 is slightly lower than that of CL-CD-MOFs-IBU-2, which may be due to the difference in IBU content between CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2.

Conclusion
This study prepared a new cross-linked CL-CD-MOFs material and based on this, prepared two drug-loaded materials, CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 by changing the order of IPDI and IBU in the reaction.The infrared spectrum results showed that IPDI was successfully cross-linked with CD-MOFs and IBU was loaded in the polymer.The XRD results showed that two samples had high crystallinity.The SEM results showed that the morphology and particle size of the material before and after crosslinking did not change significantly, but the pore size on the surface decreased due to cross-linking.TGA and nitrogen adsorption experiments showed good thermal stability and similar specific surface area of the two materials.Water stability and moisture resistance experiments showed that CL-CD-MOFs were stable in water, while CD-MOFs were easily dissolved in water.Therefore, this study improved the poor water stability of CD-MOFs by cross-linking with IPDI, while retaining the excellent characteristics of CD-MOFs.Further analysis of drug loading performance showed that CL-CD-MOFs-IBU-1 and CL-CD-MOFs-IBU-2 had high drug loading rate and encapsulation efficiency.Compared with cross-linking before loading, loading before cross-linking had a more obvious improvement in IBU loading rate and encapsulation efficiency.The in vitro drug release experiment showed that CL-CD-MOFs-IBU-1 had a longer drug release time.The MTT method was used to study the cytotoxicity of the two materials and it was found that both materials showed low cytotoxicity and good biocompatibility.Therefore, CL-CD-MOFs synthesized by IPDI cross-linking is a well-performed drug carrier with good water stability, thermal stability, and drug loading properties, which is beneficial to the development and utilization of CD-MOF in the field of biomedicine.
= ÉE Mass of drug in carrier Mass of drug fed initially % 100% = Drug loading weight of IBU Total weight of sample 100%