Introduction

Developing practical drug delivery systems (DDSs) to deliver chemotherapy agents to the tumor site towards improving the therapeutic efficacy of anti-cancer drugs is among the contesting topics of interest to researchers of various trends1. Nonetheless, the majority of employed anti-cancer drugs have poor solubility and low bioavailability, which restricts their healing effect2. Curcumin is an antioxidant agent with a polyphenol structure extracted from Curcuma long3. This moderately small molecule has been the purpose of numerous studies on compounds with anti-inflammatory, anti-cancer, antimicrobial, and free radical scavenging effects4,5. Studies confirm the capability of curcumin to prevent cardiovascular disease and cancer, improve the function of brain nerve cells, prevent Alzheimer's, and protect the liver and other organs6,7. Notwithstanding the mentioned favorable aspects, curcumin biomedical applications hindered the result of the low water solubility (11 ng/mL), bioavailability (1%), and slight cell uptake8. Curcumin can be encapsulated in nanoparticle DDSs to overcome these limitations. An innovative DDS must have a high loading capacity and controlled release capability to deliver therapeutics across the biological barrier and restrict the side effects to the patients9. Hence, high surface area and porosity, defined pore structure, placement in nano-dimensions, and so forth are among the necessities in the reticular design of drug-carrying frameworks10,11. Porous materials with unique characteristics can operate as active sites for holding guest molecules for drug delivery purposes12. COFs are a hopeful extension of porous material synthesized via covalent bonds by 2D or 3D porous crystalline structure, and the specific spatial organization of subunits gives them coveted properties13,14. Owing to abundant and tunable micro and mesopores, predictability of composition and topology, low biotoxicity and density, and biocompatible and biodegradable nature due to metal-free polymeric structure, COFs have become a prominent candidate in drug delivery applications15. Nevertheless, cavities with small pore volumes considerably lessen drug loading efficiency, leading to insufficient drug delivery16. Meanwhile, the M41S family of ordered mesoporous silica group, concentratedly, MCM-41 is among the most advised DDSs because of particular virtues including, a high degree of porosity, structural stability, narrow size distribution, huge surface area, high degree of porosity (pore volumes ranging from 0.1 to 1.5 cm3/g), and is non-cytotoxic8,17. Regarding the detailed characteristics, it seems the combination of these groups can be fruitful in overcoming the limitations of COFs application in drug delivery. Merging the hydrophilic interactions, significant pore volume, and surface area features of MCM-NH218 with π-π stacking and hydrophobic interactions, and the abundance of conjugated nitrogen atoms resulting from COF backbone19 as the active agents against pH changes can be promising to improve the active pharmaceutical ingredients (APIs) loading and release efficiency from the joined hybrid carrier.

By trusting this knowledge, this paper aims to represent the advancement of curcumin (Fig. 1) loading and delivery by applying COF/NH2-MCM-41 nanohybrid. Due to the probable toxicity when using organic solvents, nanostructure synthesis, and drug loading processes were performed based on solvent-free green methods (solid-state). The structure and properties of the as-synthesized DDSs checked out before and after C-loading. Subsequently, release profiles were assayed subject to different pH statuses. In line with this, we performed in vitro antitumor experimentation with C-loaded PI-COF/MCM-NH2 nanohybrid (termed C@Hybrid) and confirmed the proficiency to quell MDA-MB-231 human breast cancer cell viability.

Fig. 1
figure 1

Chemical structure and 3D model of curcumin, Gray corresponds to carbon, red to oxygen and to cyan color hydrogen atoms.

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Experimental section

Materials

All commercial reagents including melamine, pyromellitic dianhydride (PMDA), cetyltrimethylammonium bromide (CTAB), ethylamine (EA), tetraethylorthosilicate (TEOS), toluene, 3-Aminopropyl triethoxysilane (APTES), Methyl-thiazolyldiphenyl-tetrazolium bromide (MTT), Tween® 80 (Polysorbate), and curcumin were analytic grade reagents, purchased from Merck (Germany) and used without latter purification. Dimethylsulfoxide (DMSO), ethanol (EtOH) and the other reagents used for the washing of the as-prepared samples, were purchased from commercial suppliers' sources. Phosphate-buffered saline (PBS) salts were obtained from Sigma Aldrich. The dialysis bag (cut off 12,000 KD) was purchased from Merck Company.

Sample preparation

PI-COF synthesis method

The PI-COF nanoporous structure was synthesized per a barely modified reference procedure20. Synthesis includes directly heating the ground mixture of melamine and PMDA with a 1:1.5 molar ratio in a tube furnace subject to an Ar atmosphere. The mixture was put into a porcelain crucible and heated at 5℃/min up to 300 ℃ for 4 h. The resultant light-yellow product is well-grounded into powder and washed with warm water to remove any remaining monomer. The applied synthetic procedure was simple, green, and environment-friendly due to no solvent involved in the reaction.

Synthesis of MCM-NH2

The MCM-41 mesoporous was synthesized by a room temperature method using TEOS and CTAB as the source of silicon and structural directing template, respectively. A combination of TEA and CTAB in DI water was stirred for 30 min until a clear solution formed. The MCM-41 white gel was obtained by adjusting the pH and adding the silica source to the solution after stirring for 2 h. The product was centrifuged and rinsed with deionized water. Then, the dried powder (MCM-41) was heated with air to 550 °C for 6 h to complete surfactant elimination. The amino form of MCM-41 (MCM-NH2) was yielded via post-synthesis grafting of the APTES on MCM-41. For this purpose, 1 g of calcined MCM-41 was stirred along with 1.6 g APTES in 50 ml toluene at 60 °C for 1 h. Last, the resultant sample was dried in an oven at 80 °C for 2 h after three-times washing with dichloromethane21.

Preparation of PI-COF/MCM-NH2 mesoporous Hybrid

The PI-COF/MCM-NH2 mesoporous system was created through a during-synthesis method formulated by adding an appointed portion of MCM-NH2 to the COF-forming monomers (Fig. 2). After mechanical abrasion of the three components in the mortar, the solid was heated in an inert gas atmosphere furnace for four hours at a temperature of 300 °C. The final product was generated by drying the filtered solid in a vacuum oven at 50°C22.

Fig. 2
figure 2

Schematic representation of the synthesis of PI-COF/MCM-NH2 mesoporous hybrid.

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Drug loading and release behavior

Curcumin is loaded on mesoporous substrates of PI-COF, MCM-NH2, and the hybrid form by melting method. For this purpose, a 1:3 ratio of API:carrier was blended well in a mortar and heated for a defined time in a temperature range slightly above the melting point of curcumin. After cooling to ambient temperature, the resulting solids were washed several times with a mixture of water and ethanol and finally dried at room temperature. The loaded DDSs were named C@COF, C@MCM, and C@Hybrid. The C loading efficiency was assayed by studying the changes in the thermal behavior of the DDSs in the pure and C-presence conditions using the following equation.

$$ {\text{Drug loading content }}\left( \% \right) \, = \left( {{\text{Actual weight of API}}/{\text{Theorical weight of API taken}}} \right) \, \times { 1}00 $$
(1)

The curcumin release study using the preceding nanoformulations for the period ranging between 0.5–48 h was carried out through a dialysis bag followed by incubation in the phosphate-buffered saline solution (37 °C, 48 h) of different pH values, i.e., acidic (pH = 4.8), mildly acidic (pH = 6.5) and physiological (pH = 7.4). Drug delivery was accomplished by immersing the bag containing 8 mg API-loaded nanocarriers in 25 mL PBS. At specified time intervals, 5 mL of incubation solution was drawn for UV–Vis absorbance measurement by returned to the buffer medium immediately. The curcumin release data is kinetically analyzed in keeping with diverse model-dependent orders (Table 1). Determination of the correlation coefficients (R2) operated utilizing linear regression equations.

Table 1 Mathematical models of dissolution kinetics.
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The zero-order model describes drug systems with concentration-independent release rates. The first-order release kinetic model was utilized to check the dissolution of API encapsulated in porous DDSs. Reported by this model, the release rate is concentration-dependent23,24. The Higuchi model describes the cumulative release percentage versus the time square root-dependent process attributed to Fickian diffusion. Simultaneous penetration of phosphate-buffered simulated body fluid (SBF) into the pores, dissolution of API molecules, and release of soluble molecules from the pores constitute the release steps of the Higuchi model, respectively. The model hypotheses are the following: The drug initial-concentration in the matrix is more than its solubility; Drug diffusion is only uni-dimension; The size of drug particles is smaller than carrier thickness; Dissolution and swelling of the matrix are negligible; Drug diffusivity is constant; Sink conditions are preserved in the release system25,26. In 1931 Hixson and Crowell recognized the rate of dissolution dependence on the carrier surface-solvent contacting. Thenceforth, this model was used to investigate drug release from systems where there are changes in surface area and particle thickness. The increase in the surface area introduces faster dissolution. This model results from a simple equation examining the mechanism of drug release from polymeric systems. The empirical equation analyzes the drug's Fickian and non-Fickian release28,28. Placing the data in the Korsmeyer-Peppas equation, determining n (curve slope), and considering the geometric shape of the system, designation of the release mechanism is possible. Where n = 0, 1.0, and 0.5 indicates Zero-Order, First-order, and Higuchi model, respectively29.

Cytotoxicity evaluation

The 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was utilized to appraise the cytotoxicity of the pure curcumin, PI-COF, C@COF, MCM-NH2, C@MCM, PI-COF/MCM-NH2 hybrid, and C@Hybrid. Briefly, free curcumin and C loaded nanoporous structures with different concentrations (5, 10, and 20 µg mL-1) were added into the 96-well plates seeded with 0.02 × 106 MDA-MB-231 and MCF-10A cells (NCBI Code: C208, Pasteur institute, Iran) in RPMI-1640 medium for 24 h at 37 °C, 5% CO2 and 95% humidity. After treatments, the cells were incubated for 2 days and then the old media was removed, followed by adding MTT solution with a final concentration of 0.5 mg mL-1 to each well. Later, the cells were incubated for another 4 h in previous conditions. Last, behind medium decantation, 50 µL of DMSO was added to each well to solubilize the formed formazan purple crystals. The cytotoxicity was calculated by comparing the measured absorbance at 570 and 630 nm (Microplate Reader Biotek, ELX 800) with the control sample, and the results were rendered as the percentage of cell survival.

Characterization

The loading of curcumin was verified by characterizing the C-loaded DDSs with FTIR using a BRUKER FTIR spectrometer. The textural virtues of the nude PI-COF, MCM-NH2, hybrid, and the curcumin-impregnated carriers were characterized using N2 physisorption at 77 K on a Brunauer-Emmett-Teller (BET: BELSORP MINI II, Japan). Ahead of analysis, all the pure DDSs were degassed at 250 °C for 2 h to remove moisture and the surface filler-gases. Contrarily, drug-loaded nanoporous structures were only degassed for 2 h at 120°C to prevent leaching of the API. The structural phase identification of PI-COF, MCM-NH2, PI-COF/MCM-NH2, curcumin, and C@DDS was made via X'Pert Pro X-ray diffractometer with Cu Kα radiation (PHILIPS PW1730, Netherlands). As a supplement to the drug delivery trials, the amount of the loaded drug was determined through the TA instrument (Q600 SDT, USA). The morphology, elemental mapping, and surface characteristics of nanostructures were studied by field-emission scanning electron microscopy (MIRA3 Tescan, Czech Republic) and transmission electron microscopy (Philips, Eindhoven, Netherlands). The zeta potential of the nanostructures was analyzed using a Zetasizer (Microtrac). The UV–vis absorption spectra were measured on a T70 UV/VIS spectrophotometer (United Kingdom).

Characterizations of the pure and C-loaded DDSs

The crystal structures of the PI-COF, C@COF, MCM-NH2, C@MCM, PI-COF/MCM-NH2 hybrid, and C@Hybrid were characterized by PXRD (Fig. 3). The PXRD pattern of the PI-COF shows characteristic diffraction peaks at 18.9 and 29.5°, which are consistent with those in the literature30. X-ray diffractometry analysis of the NH2-functionalized MCM-41 particles represented three distinct diffraction peaks indexed as (100), (110), and (200), confirming the two-dimensional (2D) hexagonal mesopores31. The synthetic hybrid diffraction spectrum confirms the crystallinity of the final composition by exhibiting the characteristic peaks of constituent monomers, albeit with less intensity. Behind curcumin trapping, similar diffraction peaks were observed for the loaded DDSs, implying that the presence of API will not affect the crystallinity of the nanocarriers. Additionally, distinct tiny peaks in C@DDS XRD patterns are assigned to the curcumin.

Fig. 3
figure 3

XRD patterns of the curcumin and DDS nanoporous structures in pure and loaded forms.

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Figure 4 shows the FTIR spectra of the initial and melted form of the curcumin and pure and loaded DDSs, where the fadeaway of the band at 1850 cm−1 and intensity reduction of the bands at 1640 cm−1 and 3300 cm−1 attributed to the onset of anhydride reactions with the terminal amino groups of the starting melamine monomers. The four characteristic absorptions of the polyimide were observed at 1770, 1724, 1367, and 724 cm−1, indicating complete imidization of the product to form a polyimide21. C–H and N–H vibration bands appeared in 2900–3450 cm-1 and 1350–1750 cm-1 regions ascribed to the amine-modified MCM-41 moiety, MCM-NH2. Moreover, the symmetric and the asymmetric stretching vibration of Si-O-Si, and the bending vibration in the condensed silica framework emerged at 793, 1073, and 460 cm-1, respectively. The broad peak circa 3450 cm-1 is owned to the O-H stretching vibration of H2O molecules32. The emerged peaks of constituent monomers at 462, 701, and 1071 cm-1 concerning Si-O-Si, 1400-1600 cm-1 region related to the melamine triazine ring, the polyimide bands in 1368 and 1723 cm-1, along with the overall intensity reduction of the adsorption bands affirm the hybrid formation.

Fig. 4
figure 4

FTIR spectra of curcumin before and after the heating program, primary PI-COF, MCM-NH2, and hybrid nanoporous structures and C@DDSs.

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The similarity of the primary and fused FTIR spectrum of curcumin signifies the preservation of the API chemical structure during the loading process. The FTIR spectra of the C@DDSs possessed several peaks matching free curcumin. Most characteristic peaks are predominantly overlapping and spatial displacement. Stretching vibrations of alkenes (C=C) and carbonyl (C=O) functionalities, O-H groups, C=C aromatic stretching vibrations, mixed vibrations including in-plane bending vibrations around aliphatic and aromatic keto and enol configurations, and bending vibration of the (C-O) phenolic band have appeared about 1628, 3200-3500, 1427, 1512, and 1277 cm-1, respectively. Meantime, the magnitudes of the pure substrates' bands decreased because of C anchoring33,34.

The TEM images (a, b) and elemental mapping (c-e) of the pure DDSs shown in Fig. 5. The PI-COF coating (Fig. 5a) upon the MCM-NH2 core of the PI-COF/MCM-NH2 structure is represented clearly through the TEM image in Fig. 5b. The black central part is assigned to MCM-NH2 rod-like core, while the gray exterior part is designated to the mesoporous PI-COF shell. Elemental mapping acquired by EDX further corroborated the successful NH2-functionalization of MCM-41 and the homogeneous distribution of both monomers in PI- COF/MCM-NH2 nanoporous structures.

Fig. 5
figure 5

TEM images of PI-COF (a) and PI-COF/MCM-NH2 hybrid (b), along with elemental mapping of as-synthesized nanoporous structures: PI-COF (c), MCM-NH2 (d), and PI-COF/MCM-NH2 (e).

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FESEM micrographs of PI-COF, MCM-NH2, and hybrid form in the pure state are given in Fig. 6a–c. Regardless the aggregation, the resulting nanostructures demonstrated a size of below 100 nm with a slight increase by the addition of curcumin. MCM-41-NH2 (Fig. 6b) indicates a hexagonal structure in loosely agglomerated particles with regular shapes and a homogenous particle size distribution. The flaky-shaped with an asymmetric size distribution observes for the PI-COF sample (Fig. 6a). The FESEM images of hybrid nanoporous structure (Fig. 6c) showed scattered allocation and growth of the PI-COF layer on the MCM-NH2 outer space. DDSs comprising curcumin exhibited the same morphology as pristine in the form of filled-pores and covered surfaces (Fig. 6d–f).

Fig. 6
figure 6

Representative field emission scanning electron microscopy (FESEM) images of pure and C-loaded DDSs: PI-COF (a), MCM-NH2 (b), PI-COF/MCM-NH2 (c), C@COF (d), C@MCM (e), and C@Hybrid (f).

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A better comprehension of drug uptake profiles was made possible by N2 adsorption/desorption measurements. The results (Supplementary Fig. 1) affirm the isotherms' conformity with the Type IV isotherm of IUPAC assigned to mesoporous compounds structurally composed of both micro and larger pore sizes35. For the relative pressure of 0.0-0.2 (p/p0), the adsorption is low, micropore filling occurred. By the slight rising relative pressure, the hysteresis curve has emerged among the adsorption/desorption curves due to the multilayer adsorption and capillary condensation incidence, demonstrating that most structure's pores are mesopore36,37. Driven from the N2 adsorption isotherms, the Brunauer–Emmett–Teller (BET) surface area of pure and loaded DDSs reported in Table 2. Hybridization has resulted in an improved BET surface area and pore volume toward the PI-COF. Predictably, the curcumin-loaded nanocarriers exhibit reduced surface area and pore volume compared to the pure substrates, denoting API entrapping on the surface and within the pore structure.

Table 2 BET surface area, pore volume and average pore diameter of pure and curcumin loaded DDSs.
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The synthesized DDSs Zeta (ζ) potential measurements were executed in aqueous suspensions as a function of pH (1-9), aiming to specify the electrokinetic charge of the nanoporous structures (Supplementary Fig. 2). The purpose of measuring zeta potential is to determine the surface potential at the slipping plane placed just outside the outer surface of the particles. True to the literature values, the isoelectric points (IEP) of PI-COF and MCM-NH2 are in the 1-3 and 7.5–8.5 pH ranges, respectively21,38. The zeta potential of MCM-NH2 specified − 7.9 ± 48.49 mV down to the dominance of surface protonated NH3+ groups. The zeta potential of PI-COF declined to − 48.26 ± 8.39 mV due to the involvement of melamine amine groups in the synthesis process and hydroxyl groups induced by anhydride hydrolysis. In the PI-COF/MCM-NH2 hybrid, no IEP was observed, since the nanoporous structures show negative ζ values in the entire pH range chosen.

Investigation of the thermal stability and loading efficiency of DDSs in pure and curcumin-loaded forms was performed using TGA under an air atmosphere (Fig. 7). The first occurrence of weight loss in all substrates has manifested by moisture release (2-3%). The secondary step imputes to the decomposition of nanostructures functional groups and probably degradation of the organic polymer backbones for PI-COF and hybrid (range of 280-600 °C)39. C@Hybrid exhibited a mass-reduction of 8.99% (215-320 °C) due to the decomposition of the curcumin' substituent groups resulting in a loading percentage of 35.96%. While the mass reductions of 5.93 and 6.13% for C@COF and C@MCM, respectively, followed an entrapment percentage of 23.72% and 24.52%.

Fig. 7
figure 7

TGA curves of pure nanocarriers and curcumin (a) and C@DDS forms (b).

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Curcumin release behavior

In tumors, the pH outside the cells (pHex) and inside the cells (pHi) are typically lower compared to normal cells. Blood and normal tissues have a pHex value of around 7.4 and a pHi of approximately 7.2, while tumor cells have a slightly acidic pHex in the range of 6.0–6.5. This difference in pH can be used to trigger drug release in chemotherapy for more effective treatment of tumors. Anticancer drugs need to be released from the lysosomes to the nucleus or cytoplasm of the tumor cells. Late lysosomes and primary endosomes have pH levels of approximately 4-5 and 5-6, respectively, which are much more acidic compared to normal tissue. pH-sensitive compounds are used as stimulus-sensitive components in Nanocarriers to take advantage of these pH differences40. In this study, the pH-dependent release of curcumin from a synthetic carrier has been investigated as a controlled drug release method. The release of curcumin from three different substrates in three environments with different pHs (natural body pH 7.4, and two acidic pH 4.8 and 6.5) was studied to simulate the healthy environment, evaluating the cells in normal body conditions and the acidic environment of the cells during the period of cancer disease. The curcumin release behavior of C@DDSs was first studied in PBS at three different pH (4.8, 6.5, and 7.4) over a time course of 48 h (Fig. 8). High curcumin release (%) is observed at a pH of 4.8 (in a gradual controlled manner) for all three delivery systems. The improved drug release probably accrued owning to easily breakable interactions of curcumin and nanocarriers in an acidic environment. Herein, protonation of amine groups results in weakened hydrogen and electrostatic bonds. It is beneficial for prompting curcumin's therapeutic effects in the tumor microenvironment at acidic pH. Meanwhile, the higher release rate of MCM-NH2 compared to the COF-based carriers can be attributed to its higher surface area and smaller pore diameter pushing the drug loading mechanism more towards surface adsorption. While the reduction of free functional groups, and spatial barriers due to structural complexity, leads to a further sustained release rate of curcumin from the hybrid-form DDS.

Fig. 8
figure 8

In-vitro drug release profiles of pH-sensitive C@DDSs incubation in PBS having different values of pH 4.8, 6.5, and 7.4 for a period of 48 h.

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DDS's biocompatibility and inhibitory effect against tumor cells

MCF-10A non-tumorigenic breast cells, a model for normal epithelial cells, were subjected to exposure to free curcumin (C) and various drug delivery systems (DDSs), both with and without curcumin, to evaluate their cytotoxic profiles. After a 48-h incubation period, cell viability was assessed through the MTT assay. Results demonstrated that both free curcumin and the DDSs exhibited low toxicity towards the MCF-10A cell line at lower concentrations; however, increasing concentrations of free curcumin and curcumin-encapsulated DDSs beyond 20 μg/mL significantly induced cytotoxicity after 48 h. Importantly, DDSs lacking active pharmaceutical ingredients (APIs) curcumin showed minimal effects on cell viability, highlighting their favorable biocompatibility in this experimental context (Fig. 9). Correspondingly, the MTT assay was applied to evaluate the cytotoxicity of the initial API, pure and loaded DDSs nanoporous structures on the MDA-MB-231 breast cancer cell line (Fig. 10). Behind 48 h of exposure, C-loaded nanocarriers displayed dose-dependent cytotoxicity. All the C@DDS types revealed significantly more cytotoxic effects than free curcumin in the mentioned incubation time. Poor solubility of curcumin probably restricts API internalization into cells, while the uptake of DDSs probably resulted in further efficient curcumin accumulation and superior cytotoxicity of C@DDSs. The MTT results exhibit no considerable cytotoxicity after 48 h of treatment with blank PI-COF, MCM-NH2, and PI-COF/MCM-NH2 hybrid concluding DDS nanoporous structures are biocompatible carriers and play no role in MDA cells toxicity. Altogether, the results certify the potential of C@DDSs for curcumin delivery by increasing the effectiveness of controlled delivery.

Fig. 9
figure 9

In vitro cytotoxicity of different concentrations of free curcumin (C) and various drug delivery systems (DDSs), both with and without curcumin (5, 10, and 20 μg/mL) on MCF-10A non-tumorigenic breast cells after 48 h incubation time using MTT assay.

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Fig. 10
figure 10

Cytotoxicity of free and C loaded DDS nanoporous structures measured by MTT assay in MDA-MB-231 cells after 48 h incubation.

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Studying the kinetics of drug release

To investigate API release kinetics and mechanism, the curcumin release data fitted with the Zero and First-ordered release Kinetics, Higuchi, Korsmeyer-Peppas, and Hixson-Crowell mathematical models (Fig. 11). Most of these models depend on the diffusion equations placed on the nanostructures' composition and conditions of release. The Korsmeyer-Peppas model was also employed to study the type of curcumin diffusion in carriers plus the relevance of the surface properties and release rate. After fitting the experimental release data (pH = 7.4) into mentioned kinetic models, the release profile of C@MCM showed best-fitted with the first-order model indicating the API release was directly proportional to the curcumin content. Meanwhile, it found that the release profile of curcumin from the drug-loaded PI-COF and hybrid nanoporous structure followed the Higuchi model through the highest value of regression coefficients. These results imply that diffusion is the main driving force for curcumin release from both C@COF and C@Hybrid. The study of release kinetics at pH 4.8 and 6.5 represented similar consequences. To further confirm the rate-controlling mechanism of C@DDS formulations, the data then fitted to the Korsmeyer–Peppas equation. The most significant API release mechanisms of commercially accessible products are Diffusion, swelling, and erosion41. As for the ‘n’ values of the Korsmeyer-Peppas model (nC@COF = 0.613, nC@MCM = 0.539, and nC@Hybrid = 0.560), it was clarified the release at 7.4 pH followed anomalous diffusion (0.45 < n < 0.8), which is a combination of both diffusion and swelling controlled release.

Fig. 11
figure 11

Drug release data fitted to various kinetic models: Zero order; First order; Higuchi model; Hixson-Crowell model; and Korsmeyer-Peppas drug diffusion model (pH = 7.4).

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Conclusions

To summarize, we successfully synthesized a novel pH-responsive PI-COF/MCM-NH2 nanocarrier with a sustained release rate for efficient drug delivery of cancer. As-prepared hybrid DDS presented a more promising property than individual monomers in terms of the drug capacity and release. Both curcumin-loaded constituents' agents and hybrid form nanoporous structure exhibit pH responsiveness with a slower drug release at the physiological environment toward the acidic buffer solution promising the release accomplished in a controlled pattern. Confirming the results, hybrid DDS can act as a delay-retainer to prevent curcumin premature release during drug delivery in different pH conditions. Further, in vitro experiments indicated the considerable anticancer efficacy of C@Hybrid compared with free API, especially in low concentrations. Obtained results demonstrated that the designed novel biocompatible nanohybrid could potentially operate as a secure delivery vehicle.