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Ritika Puri
and Vimal Arora*
University Institute of Pharma Sciences, Chandigarh University, Gharuan (Mohali), Punjab, India.
Corresponding Author E-mail:draroravimal@gmail.com
Article Publishing History
Article Received on : 26 Mar 2025
Article Accepted on :
Article Published : 15 Sep 2025
Curcumin, a natural polyphenol with significant anticancer effects, is hindered by low bioavailability and quick metabolism, restricting its therapeutic application. To overcome these challenges, present study emphasizes on the synthesis of curcumin-loaded magnetic nanoparticles (Cur-MNPs) using the co-precipitation method. Poloxamer F-68 was employed as a biocompatible polymer coating to enhance stability and drug delivery efficiency. The synthesized magnetic nanoparticles were evaluated using dynamic light scattering (DLS) for particle size and zeta potential analysis, and scanning electron microscopy (SEM) for surface morphological and structural analysis. The average particle size was found to be in the nanometer range (199.3 nm), indicating suitability for cellular uptake, with a negative zeta potential of -20.4 mV suggesting colloidal stability. SEM images showed uniformly distributed, spherical nanoparticles. The synthesis curcumin-encapsulated magnetic nanoparticles exhibited a high drug encapsulation of 98.56%. The results demonstrate that Cur-MNPs synthesized via the co-precipitation method and coated with Poloxamer F-68 exhibit desirable physicochemical characteristics for targeted cancer therapy, offering a promising solution for improving curcumin delivery and therapeutic efficacy. Further animal studies can be performed to evaluate anticancer activity.
KEYWORDS:Cancer; Curcumin; Iron-Oxide; Magnetic Nanoparticles; Targeted Delivery
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Copy the following to cite this article:Puri R, Arora V. Curcumin-Encapsulated Magnetic Nanoparticles: A Promising Nanoplatform for Cancer Drug Delivery. Orient J Chem 2025;41(5).
Puri R, Arora V. Curcumin-Encapsulated Magnetic Nanoparticles: A Promising Nanoplatform for Cancer Drug Delivery. Orient J Chem 2025;41(5). Available from: https://bit.ly/3VkaegR
Introduction
Cancer, a complicated, complex and severe illness characterized by the unregulated growth and proliferation of atypical cells in the body. It is a prominent source of disease and mortality globally, presenting substantial difficulties to both public health systems and individuals. According to the data published by the International Centre for Research on Cancer in 2022, approximately 1.4 million incidence cases (Figure 1) and 9 million deaths due to various types of cancers have been reported. Breast cancer is the leading cause of cancer death, accounting for roughly 98337 deaths (10.7%), followed by lip, oral cavity (8.7%), cervix uteri (8.7%), lung cancer (8.2%), oesophagus (7.2%) and stomach cancer (6.3%) as depicted in Figure 2.1,2
Figure 1: Data representing the incidence cases reported in India due to various types of cancer (Year 2022).
Figure 2: Data representing mortality cases reported in India due to various types of cancer (Year 2022)
Cancer pathogenesis is a complex phenomenon and an interrelated set of biological mechanisms that convert normal cells into malignant ones. Genetic mutations, oncogene activation, inactivation of tumor suppressor genes, and epigenetic alterations primarily contribute to uncontrolled cell proliferation. Over time, these aberrant cells progress through hyperplasia, dysplasia, and carcinoma in situ, finally gaining the capacity to infiltrate surrounding tissues and metastasize to distant organs, causing advanced cancer.3 Existing therapies for the treatment of cancer, such as surgery, radiation, chemotherapeutic agents, hormonal therapy, and stem cell transplant, are in daily practice but are not able to achieve the desired therapeutic effects due to one or another reason. One key difficulty is the emergence of resistance to both chemotherapy and targeted therapies, reducing their long-term efficacy. Personalized therapy remains difficult due to tumor heterogeneity and a lack of accurate biomarkers for predicting patient response. Side effects such as fatigue, hair loss, nausea, and an increased risk of infection and toxicity, particularly those associated with chemotherapy and radiation, have a substantial influence on patients’ quality of life. Moreover, the early diagnosis of cancer is consistently challenging, sometimes due to the silent onset of the disease or diagnoses occurring at advanced stages, which complicates treatment.4 Most of the anticancer cancer drugs don’t get into the tumor microenvironment effectively, which could make it harder to distribute them in a proper manner. Secondly, the cost of anticancer drugs, immunotherapy and targeted therapy available commercially is very high.5
Nanocarriers act as promising approach or technique for the conveyance of drugs to the specific site and to improve patient compliance by minimizing the side effects and decreased dosage regimen. Several therapeutic agents could not show the particular effect due to the drawback of specific targeting to the designated area which results critical side effects because of high dose concentration.6 This transporting system of colloidal drug with their particle size <500 nm makes it beneficial to modify the bioactivity of drugs. Various nanocarriers, including nanoparticles, nano-tubes, and lipid-based carriers, influence the pharmacokinetic profile of active drugs by safeguarding them from degradation, facilitating higher concentration of administered drugs in target tissues, and mitigating undesirable side effects. Magnetic nanoparticles (MNPs) are a potential way to deliver drugs since they may be directed to specific parts of the body and may or may not be controlled by external magnetic fields. This targeted delivery can enhance patient outcomes, reduce side effects, and augment therapeutic efficacy.7
Curcumin, a naturally occurring polyphenolic molecule, is the principal bioactive element in the rhizome of the turmeric plant, Curcuma longa, which is a member of the Zingiberaceae ginger family. Curcumin has recently garnered significant interest among scientists due to its numerous pharmacological properties and potential medical applications, particularly in cancer prevention and treatment. Because of its beneficial pharmacological properties, it is the subject of several research studies, clinical trials, and scientific inquiries.8 Its pleiotropic properties stem from its capacity to modulate several signaling pathways and biological targets associated with disease etiology. Curcumin has been found to limit angiogenesis (the building of new blood vessels), cause apoptosis (planned cell death), stop cancer cells from growing, and stop metastases. Curcumin has been demonstrated to enhance the efficacy of conventional cancer treatments, such as chemotherapy and radiation therapy, while mitigating their adverse effects. Additionally, curcumin exhibits synergistic interactions with other advantageous compounds, suggesting its potential as an adjunctive therapy in cancer treatment.9 A novel and promising approach to cancer treatment is achieved by combining the beneficial properties of iron oxide magnetic nanoparticles with the therapeutic properties of curcumin. Curcumin’s intrinsic drawbacks, including poor bioavailability, fast metabolism, and instability, are intended to be solved through curcumin-loaded iron oxide magnetic nanoparticles. As a protective carrier, the iron oxide magnetic nanoparticles improve stability of curcumin and solubility, increasing its bioavailability and guaranteeing a prolonged release.10
Materials
Curcumin (API, 99%), ferric chloride and ferrous sulphate were obtained from Central Drug House (CDH) Pvt. Ltd. in Delhi. Poloxamer-F68 (Pluronic®F68) was purchased from HiMedia Laboratories, Mumbai, India. Every other chemical utilized in the investigation was acquired from nearby suppliers and is of analytical grade.
Methods
Development of Magnetic Nanoparticles
This study involved a three-step process: the synthesis of iron-oxide nanoparticles by the co-precipitation method, coating of the iron-oxide magnetic core, and the subsequent drug loading. This method ensures uniform particle size and distribution, and crucial for the desired application.10
Preparation of Magnetic Nanoparticles (core) by Co-precipitation Method
Ferrous sulfate tetrahydrate and ferric chloride hexahydrate were prepared in molar ratio of 1:2 to prepare the Fe3O4 nanoparticles by the co-precipitation method as illustrated in Figure 3 and continuously sonicated using a probe sonicator (LabMan Pro 650) at 65°C followed by dropwise addition of ammonium hydroxide solution into the prepared mixture till the color changed from brown to black and pH reaches to 12.11 Stirring was continued for 30 minutes, and then the mixture was continuously purged with N2 for an additional 10 minutes. The precipitates were then kept aside for 12 hours at room temperature for proper settling down followed by centrifugation and multiple washes with triple-distilled water. The collected precipitate was then dried at 60°C in a vacuum oven for 1 hour. The final product, Fe3O4-NP, was obtained as a black powder.
Chemical reaction is expressed as:
4FeSO4+2FeCl3+10NH4OH → Fe3O4 +8NH4Cl+10H2O
Figure 3: Schematic representation of synthesis of magnetic nanoparticles core by Co-precipitation method
Coating of Iron-Oxide Magnetic Nanoparticles
To carry out this step, 1%w/v solution of Poloxamer F-68 was prepared by dissolving it in distilled water at approximately 40±0.5˚C, and approximately 40mg of magnetic core was added to the prepared coating solution and continuous stirring was performed using a magnetic stirrer for 10 hours so that coating solution can cover surface of magnetite core. Coated particles were separated by performing centrifugation and dried in the vacuum oven at 40±2˚C.
Drug Loading in Synthesized Magnetic Nanoparticles
Curcumin drug-loading was carried out by dispersing 100mg of polymer-coated magnetic nanoparticles in water and setting on the magnetic stirrer (Remi Lab World, Mumbai) at 1500 rpm. In another beaker, 20 mg of curcumin was dissolved in methanol and incorporated into the coated-MNPs solution under continuous stirring for 24 hours to facilitate drug uptake. After 24 hours, MNPs were collected using the magnet, washed with distilled water, and dried using a vacuum oven at 60˚C.
Characterization of Developed MNPs
Physicochemical and Morphological Characterization
Particle Size Analysis and PDI
Using a Malvern Zetasizer (Model: Ver.7.11), particle size analysis and the polydispersity index (PDI) of the synthesized iron-oxide magnetic nanoparticles and curcumin-loaded iron-oxide magnetic nanoparticles were performed. To carry out this analysis, dispersion of the magnetic nanoparticles is formed using distilled water as a vehicle. Sample is placed in the cuvette to analyze the dispersion using dynamic light scattering (DLS).12 The results are represented as mean±SD (n=3).
Determination of Zeta Potential
Malvern Zetasizer (Model: Ver.7.11) was used to measure the zeta potential of the iron-oxide magnetic nanoparticles and the curcumin-loaded iron-oxide magnetic nanoparticles. This let us find out their surface charge on the synthesized particles and colloidal stability. To measure the zeta potential, nonodispersion was prepared by taking the 10 mg of magnetic nanoparticles followed by dilution with distilled water in the testtube. Electric field was applied upon the nanodispersion by the instrument leading to movement of charged particles towards electrode with opposite charge. Depending on the movement of charged particles, zeta potential of the sample was measured by the system.13 The results are represented as mean±S.D (n=3).
Scanning Electron Microscopy (SEM)
Scanning electron microscopy (SEM) analysis of the synthesized iron-oxide magnetic nanoparticles and curcumin-loaded iron-oxide magnetic nanoparticles was carried out using a SEM (Model: JSM IT500) to investigate their morphological and surface properties. SEM allows for the thorough investigation of the structure of the nanoparticles by scanning the sample surface with a concentrated electron beam to produce high-resolution images. To avoid charging under the electron beam, a thin layer of gold was applied to a conductive substrate after a small portion of the nanoparticle sample was spread out over it for this examination.14
Encapsulation Efficiency
Millipore centrifugal tubes were employed to ascertain the quantity of free curcumin in the nanodispersions. The filtrate was collected by centrifuging the nanodispersion at 10,000 rpm for 60 minutes. The concentration of free curcumin in the supernatant was ascertained using high-performance liquid chromatography at λmax of 428 nm after the sample was diluted appropriately. Following equation was employed for the determination of the percent entrapment efficiency:
In-vitro Drug Release Study
The In-vitro drug release study of both curcumin-loaded (without coating solution) and curcumin-loaded polymer-coated iron oxide magnetic nanoparticles was conducted using a dialysis bag method. To perform this study, initially the dialysis bags were activated by soaking them in phosphate buffer (pH 7.4) for 24 hours to ensure the pores of the membrane were fully opened, facilitating the diffusion study. Each activated dialysis bag was filled with 5 mL of either curcumin loaded or curcumin with polymer-coated iron oxide nanoparticles. The bags were then securely sealed at both ends with cotton thread to prevent leakage. These prepared dialysis bags were placed into separate beakers containing phosphate buffer (pH 7.4) and kept at 37±2°C with constant stirring at 100 rpm. Samples were taken from the beakers at various intervals while maintaining the sink condition throughout the process. Filtrate was analysed using HPLC at 428 nm. A graph was then plotted to depict the release profile of the prepared drug-loaded MNPs over time.16
Results and Discussion
Particle Size Analysis and PDI
The particle size and PDI analysis of synthesized iron-oxide magnetic nanoparticles and curcumin-loaded iron oxide magnetic nanoparticles depicted in Figure 4 reveal that the iron-oxide MNPs exhibited an average hydrodynamic diameter of 199.3 nm and a polydispersity index (PDI) of 0.294, suggesting a uniform size distribution and well-controlled synthesis, while the curcumin-loaded MNPs showed a larger average size of 205.6 nm with a slightly lower PDI of 0.265. These findings suggest that curcumin loading increases particle size, likely due to absorption of coating solution and drug on the core surface.17
Figure 4: Particle size determination of a) Bare iron-oxide magnetic nanoparticles b) Curcumin-loaded iron-oxide magnetic nanoparticles.
Determination of Zeta Potential
The zeta potential measurements of both synthesized iron-oxide magnetic nanoparticles and curcumin-loaded magnetic nanoparticles are of primary importance to ensure the stability of the nanoparticles.18 The iron-oxide magnetic nanoparticles exhibited a zeta potential of -18.5 mV, demonstrating a moderate surface charge that offers adequate electrostatic repulsion, avoiding agglomeration and ensuring stability in aqueous environments. Similarly, the curcumin-loaded magnetic nanoparticles demonstrated a zeta potential of -20.4 mV, indicating a substantial surface charge with strong electrostatic repulsion, improving their dispersion stability as illustrated in Figure 5.
Figure 5: Zeta potential determination of a) Bare iron-oxide magnetic nanoparticles b) Curcumin-loaded iron-oxide magnetic nanoparticles.
Scanning Electron Microscopy (SEM)
SEM images revealed a range of particle shapes and sizes, including spherical and irregular forms, with relatively smooth surfaces and some aggregated clusters (Figure 6). The magnetic nanoparticles were predominantly irregular in shape, with a homogeneous size distribution and a generally smooth surface, though minor surface irregularities were observed. The well-dispersed clusters suggest effective incorporation of curcumin into the iron-oxide matrix.19
Figure 6: Scanning Electron Microscopy images of curcumin-encapsulated iron-oxide magnetic nanoparticles.
Encapsulation Efficiency
The optimized curcumin-loaded iron oxide magnetic nanoparticles exhibited a high drug encapsulation efficiency of 98.56%. This impressive level of entrapment indicates that nearly all of the drug was successfully incorporated into the magnetic nanoparticles, which minimizes drug loss and enhances the formulation’s therapeutic potential. Such high encapsulation efficiency is crucial for maximizing drug delivery effectiveness, reducing required dosages, and minimizing side effects.20
In-vitro Drug Release Study
The in vitro drug release study of formulated curcumin-loaded iron oxide magnetic nanoparticles compared two formulations: curcumin-loaded iron oxide magnetic nanoparticles (without coating solution) and curcumin with polymer-coated iron oxide magnetic nanoparticles. The formulation of curcumin-loaded iron oxide nanoparticles (without coating solution) exhibited a rapid initial burst release, releasing about 43.5% of the drug within 10 hours. In contrast, curcumin with polymer-coated iron oxide nanoparticles demonstrated a more controlled release profile, releasing 20% of drug in 10 hours then releasing 48.7% of the drug in 24 hours. The polymer effectively modulates the release rate, providing a gradual and consistent release, which is ideal for maintaining steady therapeutic levels over time.21-23 These findings highlight the impact of polymer coating on optimizing drug release kinetics, as illustrated in Figure 7.
Conclusion
Despite numerous drawbacks of chemotherapeutic agents, including their impact on healthy cells and drug resistance, these medications are successful in decreasing the survival of cancer cells. Furthermore, continuous intravenous infusion is frequently employed because of the rapid catabolism and brief half-life of these medications. Drug loading in targeted nanoparticles can be used to overcome the aforementioned challenges. The non-specific effects of curcumin on healthy cells can be mitigated by encapsulating it within iron-oxide nanoparticles, which are produced through the co-precipitation method and subsequently coated with Poloxamer F-68. The synthesized iron oxide magnetic nanoparticles, which are loaded with curcumin, exhibit a spherical morphology and have a size distribution of 200 to 300 nm. The findings from this research indicate that the spherical structure of the prepared drug-loaded magnetic nanoparticles demonstrates significant potential for the delivery of drugs to tumor cells.
Funding Sources
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
The author(s) do not have any conflict of interest.
Data Availability Statement
This statement does not apply to this article.
Ethics Statement
his research did not involve human participants, animal subjects, or any material that requires ethical approval.
References
Raj M, Priya M, Singh HK, Swain S. Cancer death scenario: A brief concept on cancer related deaths. Indian J Pharm Pharmacol 2024;10(4):246–52. doi:18231/j.ijpp.2023.043.Visited 1 times, 1 visit(s) today
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