Synthesis of High-Precision Sub-Micron CaCO₃ Anticancer Drug Carriers from Coral Remains

Abstract

Calcium carbonate (CaCO₃) particles have attracted increasing attention as a promising material for drug delivery systems. In this study, coral remains were utilized as a raw material for a novel drug carrier. A series of pre-treatment and parameter experiments were conducted to synthesize sub-micron spherical CaCO₃ particles. The CaCO₃ particles exhibited uniform size distribution, with the minimum mean size being only 344 nm. The effects on the CaCO₃ crystal phases and particle sizes were also discussed in this study. Drug loading experiments were also conducted to assess the feasibility of the CaCO₃ drug carrier. We loaded TRITC-Dextran into CaCO₃ particles for the simulation experiments. The loading capacity reached up to 9.6 wt.%, which was as high as common drug carriers such as liposomes. In this study, we aimed not only to tackle the local environmental issues caused by coral remains, but also to synthesize a suitable drug carrier for cancer therapy using the outstanding properties and low cost of CaCO₃.

1. Introduction

Environmental degradation and disease are the two major challenges of this century. This study explores a novel solution to deal these issues by addressing the accumulated coral remains in Taiwan and their potential application in cancer drug development, one of the leading causes of death worldwide. Coral remains are composed of coral fragments resulting from weathering, waves, or trampling. It is a unique environmental issue in Taiwan. Despite coral remains being non-toxic and harmless, the accumulation of coral causes lots of problems along the coast in Penghu, one of the counties in Taiwan. Coral remains accumulating along the coast lead to a reduction in marine life living spaces and the obstruction of fishing routes, impacting fishermen’s livelihoods. The local government tried to dredge the coral remains and place them onto the beach. Unfortunately, the resulting odor and damage to the landscape continued to constitute serious problems. Coral remains consist of CaCO₃, which is known as a safe, cheap, and clean industrial mineral. Compared to oyster shells, coral remains do not require a significant amount of time for washing and cleaning, making them an ideal material for this study.

Cancer is one of the most critical issues around the world. The International Agency for Research on Cancer (IARC) and the Union for International Cancer Control (UICC) reported nearly 19.3 million cancer cases, with the death toll reaching up to 10 million in 2020 [1]. Moreover, cancer has been the leading cause of death in Taiwan since 1982, accounting for 28.98% of all deaths in 2020, totaling 50,161 people [2]. Due to the toxicity of cancer drugs, the precision of drug delivery is a significant feature in curing cancers. Therefore, a growing amount of research is committed to loading drugs into unique containers to improve the precision of drug delivery, i.e., drug carriers [3,4]. There is currently a variety of drug carriers such as liposomes, solid lipid nanoparticles, gold nanoparticles, etc. However, they still have some critical problems that must be dealt with, e.g., bio-toxicity, aggregation, and high cost.

CaCO₃ is a promising and novel material for drug carriers. It possesses several properties, including high biocompatibility, substantial drug loading capacity, pH sensitivity, low cost, and the capability to carry multiple drugs simultaneously [5,6,7,8,9]. It is widely used as an industrial mineral [10,11,12,13,14,15,16,17,18,19] and a raw material for pharmaceutical products [20,21]. CaCO₃ has been utilized as a carrier to deliver proteins and genes [22]. Therefore, the public acceptability of CaCO₃ is better than that of other materials. Moreover, according to the report from Vikulina et al. [23], CaCO₃ costs only 0.2–0.4 USD/g, which is significantly lower than the 100 USD/g cost of liposomes.

CaCO₃ is widely used in industry as a filler. It can not only lower the cost but also improve the properties of products [24,25]. CaCO₃ has three major anhydrous phases: calcite, aragonite, and vaterite [26,27]. Calcite is the most stable phase among them, followed by aragonite and vaterite [28,29,30,31]. Vaterite is the least stable but the most promising phase for a drug carrier due to its high porosity, large surface, and higher solubility. Vaterite will gradually dissolve and recrystallize into calcite in water, which is an imperative mechanism for drugs to be released from vaterite (Figure 1). Owing to the instability of vaterite, the synthesizing process must be studied to control the morphology, particle size, and purity of it. To manipulate the morphologies and particle sizes of CaCO₃, the addition of additives is the general approach for achieving this [32,33,34,35,36,37,38]. Parakhonskiy et al. reported that polyol can inhibit CaCO₃ from growing into other phases [39]. Thus, we used ethylene glycol (EG) as an additive to maintain the vaterite phase [40,41,42]. EG can also control the particle size of vaterite, as studies have indicated that cancer cells take up molecules smaller than 600 nm selectively due to the enhanced permeability and retention effect (EPR effect) [43].

2. Materials and Methods

2.1. Materials

Coral remains from Penghu coastal accumulations and dredging operations were used as the raw material for this study. Coral remains were collected by scholars from Penghu University of Science and Technology. The dredging operations were carried out by the Penghu government. The coral remains were dredged and placed along the coast so that we could easily collect them with permission from the government.

2.2. Pretreatment and Characteristic Analysis of Coral Remains

Coral remains underwent washing, hydrogen peroxide immersing, drying, and grinding, followed by 60-mesh sieving. For elemental analysis, the sample was calcined at 1000 °C for 4 h, then dissolved in a mixture of aqua regia and hydrofluoric acid (HF) in the ratio of 9:1. Following these procedures, the solution was analyzed using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES, Avio 200 Manx, PerkinElmer, Waltham, MA, USA).

2.3. Purification of Coral Remains and Preparation of CaCl₂

Purification began with the calcination of coral remains at 1000 °C to decompose them into CaO, which was then dissolved in water to form Ca(OH)₂. This step was followed by a reaction with CO₂, resulting in the precipitation of CaCO₃. The calcination was carried out in a tube furnace under different atmospheres (air, N₂, and CO₂) to study the decomposition rate of CaCO₃ in varying conditions. The calcination temperatures in air and N₂ were set between 700 °C and 1200 °C. In the case of CO₂, temperatures ranged from 500 °C to 1000 °C due to no significant improvement observed beyond 700 °C, prompting the extension down to 500 °C. The decomposition rates of CaCO₃ were calculated using the following equation (Equation (1)), where x represents the decomposition rate and 44 is the molecular weight of CO₂. The purity of the resulting CaCO₃ was confirmed using ICP-OES, and it was subsequently reacted with HCl to produce CaCl₂, as shown in the following equations (Equations (2) and (3)):

$$\mathrm{x}=(\mathrm{mass} \mathrm{of} {\mathrm{CaCO}}_3-\mathrm{mass} \mathrm{of} \mathrm{CaO})/44$$

(1)

$${\mathrm{CaCO}}_{3\left(\mathrm{s}\right)}+2{\mathrm{HCl}}_{\left(\mathrm{aq}\right)}\to {\mathrm{CaCl}}_{2\left(\mathrm{aq}\right)}+{\mathrm{CO}}_{2\left(\mathrm{g}\right)}+{\mathrm{H}}_2{\mathrm{O}}_{\left(\mathrm{l}\right)}$$

(2)

$${\mathrm{CaCl}}_{2\left(\mathrm{aq}\right)}\stackrel{\Delta }{\to }{\mathrm{CaCl}}_{2\left(\mathrm{s}\right)}$$

(3)

2.4. Exploration of Optimal Parameters for the Synthesis of Vaterite

Solutions with different concentrations of CaCl₂ and Na₂CO₃ were prepared and injected into EG in specific ratios. Further steps included centrifugation, washing, and drying at 60 °C for 2 h. Given the complex reaction mechanism involved in vaterite formation, a thorough investigation was conducted to gain a comprehensive understanding of its reaction mechanisms and characteristics. This involved exploring a range of parameters, such as the concentration of EG, stirring speed, total reaction time, initial salt concentration, reaction volume, and the adding order of CaCl₂ and Na₂CO₃. The particle size and crystal phase variations of CaCO₃ under these different conditions were carefully observed to identify the optimal synthesis parameters. For examining the vaterite crystal structure, Scanning Electron Microscopy (SEM, Hitachi SU-1510, Tokyo, Japan) was utilized, with the samples being coated with a palladium (Pd) layer. The particle size distribution was quantified using ImageJ Version 1.54h, with a sample size of N $\ge$ 150 particles per sample.

2.4.1. Adding Order of the Salts

CaCO₃ was synthesized using the precipitation method, involving CaCl₂ and Na₂CO₃. We found that the order in which these salts are added plays a critical role, a parameter not extensively discussed in the existing literature. Altering the sequence of adding CaCl₂ and Na₂CO₃ resulted in significant variations in the crystal forms and particle sizes of the synthesized CaCO₃. Therefore, the impact of the adding order of these salts was emphasized in this study.

2.4.2. Stirring Speed

This section examined the effect of various stirring speeds (400, 600, 800, 1000, and 1150 rpm) on the particle size of CaCO₃.

2.4.3. EG Concentration

Ethylene glycol (EG) played a critical role in this study due to its high viscosity, which decelerates ion diffusion and inhibits the growth of CaCO₃. We investigated various EG concentrations, including 0%, 25%, 50%, and 85%, to determine their impact on the synthesis of CaCO₃.

2.4.4. Reaction Time

The presence of EG is known to mitigate the reaction speed. We explored how varying reaction times influence the diversity of CaCO₃ formations. In this study, time intervals of 1 min, 30 min, 60 min, 180 min, and 1440 min (1 day) were examined to determine the optimal reaction duration.

2.4.5. Initial Salt Concentration

Nucleation theory suggests that the initial salt concentration can impact the nucleation rate, consequently affecting the particle size. This study varied the initial concentrations of CaCl₂ and Na₂CO₃ to observe the resulting changes in CaCO₃ and to validate the alignment of our findings with the nucleation theory.

2.4.6. Total Reaction Volume

This investigation explored the effects of different total reaction volumes, including the combined volumes of salt solutions and EG. Contrasting with the common practice in the literature, which typically synthesizes CaCO₃ using drug carriers around 100 mL, we extended this range to include volumes of 4 mL, 40 mL, 120 mL, and 400 mL to investigate the formation and characteristic of CaCO₃.

2.5. Drug Loading Simulation Experiment

The fluorescently labeled drug Tetramethylrhodamine Isothiocyanate–Dextran (TRITC-Dextran) was utilized for loading into CaCO₃ carriers, and the loading capacity (LC) was subsequently calculated after drug loading. For LC calculation, an indirect method [44] was employed. This method involves analyzing the concentration of the drug in the supernatant collected after centrifugation the drug-loaded carrier. The LC is then estimated by deducting the drug concentration in the supernatant from the initial drug concentration. The concentration of TRITC-Dextran was maintained at 10 mg/mL in this study. We analyzed the collected supernatant using a Fluorescence Spectrophotometer (Fluorescence Spectrophotometer, Hitachi High-Tech F-7000, Hitachi High-Technologies Corporation, Tokyo, Japan). The drug-loaded carriers were examined under a confocal microscope (Confocal Microscope, Carl Zeiss LSM780, Carl Zeiss AG, Oberkochen, Germany) to assess the amount of TRITC-Dextran loaded into the CaCO₃ particles. An excitation wavelength of $\lambda =530$ nm was utilized in this study. The drug concentration in the supernatant was calculated using the following equation (Equation (4)):

$$\mathrm{F}={\mathrm{P}}_0\left(2.3\mathsf{\epsilon }\mathrm{b}\mathrm{c}\right){\mathrm{Q}}_{\mathrm{f}}\mathrm{k}$$

(4)

where $\mathrm{F}$ represents the intensity of fluorescence, ${\mathrm{P}}_0$ is the incident power, $\mathsf{\epsilon }$ is the molar absorptivity, $\mathrm{b}$ is the path length, $\mathrm{c}$ is the concentration, ${\mathrm{Q}}_{\mathrm{f}}$ is the quantum efficiency, and $\mathrm{k}$ is the ratio of photons measured to photons emitted. Typically, ${\mathrm{P}}_0$, $\mathsf{\epsilon }$, b, ${\mathrm{Q}}_{\mathrm{f}}$, and k are constant, making the concentration in the supernatant directly proportional to the fluorescence intensity F.

3. Result and Discussion

3.1. Characteristic Analysis of Coral Remains

Table 1. Composition of raw coral remains.

Ingredient	Proportion
CaO	92.95123%
MgO	3.67358%
MnO2	0.00300%
Fe2O3	0.47249%
SiO2	2.13416%
Al2O3	0.77554%
PbO	N/A
CdO	N/A

and

Table 2. Composition of purified coral remains.

Ingredient	Proportion
CaO	99.96482%
MgO	0.00158%
MnO2	0.00006%
Fe2O3	0.00035%
SiO2	0.01910%
Al2O3	0.01409%
PbO	N/A
CdO	N/A

present the elemental composition of the raw and purified coral remains, as determined by ICP-OES. The raw coral remains primarily consisted of elements such as Ca, Mg, and Si, with no detectable levels of Pb and Cd. After purification, the purity of CaO significantly increased from 92.95% to 99.965%, indicating the effective removal of most impurities. This aligns with the 2023 Republic of China National Regulations Database standards for CaCO₃ (§ 07014) [45], particularly for use in food and nutrition applications. These standards require a CaCO₃ content of over 98%, less than 0.2% hydrochloric acid insoluble residue, and lead levels below 10 ppm. Consequently, the purified coral remains qualify as food-grade additive.

3.2. Purification of Coral Remains and Preparation of CaCl₂

The calcination efficiency of coral remains under different atmospheres is shown in Figure 2a–c. The decomposition rate of CaCO₃ to CaO in an N₂ atmosphere showed a significant increase, achieving complete reaction in just 5 min at 800 °C, compared to the 15 min required at 900 °C in an air atmosphere. In a CO₂ atmosphere, the decomposition rate experienced a slight increase and stabilized after reaching 700 °C. However, the decomposition rate plateaued at 13%, even after extending the duration to 30 min at 1000 °C. This could be attributed to the Le Châtelier’s principle, where the high partial pressure of CO₂ generated during the calcination process inhibited further decomposition. Conversely, in the N₂ atmosphere, the inert gas was continuously removed from the system with the simultaneous introduction of N₂, facilitating a decomposition rate reaching 100% in just 5 min at 800 °C. These findings verified the theory that CO₂ partial pressure significantly affects the efficiency of decomposition. Therefore, based on the results, an N₂ atmosphere was determined to be the optimal condition for calcination.

3.3. Exploration of Optimal Parameters for the Synthesis of Vaterite

3.3.1. Adding Order of the Salts

This step explored the effects of the different adding orders of the salts on the synthesis of CaCO₃, with operational parameters detailed in

Table 3. Parameters for reaction base experiment.

Factors	Parameters
Adding Order	CaCl2-first, Na2CO3-first
Stirring Speed (rpm)	1000 rpm
Concentration of EG	85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.1 M
Reaction Volume (mL)	4

. The SEM results depicted in Figure 3 reveal that adding CaCl₂ before Na₂CO₃ significantly affects the particle size, resulting in a more uniform distribution compared to adding Na₂CO₃ before CaCl₂. The average particle size for CaCl₂-first was found to be 423 nm, compared to 869 nm for Na₂CO₃-first. Consequently, CaCl₂-first was chosen as the optimal parameter for subsequent reactions.

3.3.2. Stirring Speed

This step investigated the impact of different stirring speeds on the particle size of CaCO₃, with the operational parameter outlined in

Table 4. Parameters for stirring speed experiment.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	400, 600, 800, 1000, 1150
Concentration of EG	85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.1 M
Reaction Volume (mL)	4

. As shown in Figure 4a, an increase in stirring speed corresponded with a reduction in the average particle size of CaCO₃. Notably, at 400 rpm, the formation of numerous calcite particles and some particle aggregation was observed (Figure 4b); as a result, the data obtained from this speed setting was deemed unsuitable in our discussion. At a speed of 1150 rpm, the particle size was reduced to an average of 364 nm, making it the optimal parameter.

3.3.3. EG Concentration

This step examined the effect of different EG concentrations on the particle size and crystal growth of CaCO₃, with operational parameters detailed in

Table 5. Parameters for EG concentration experiment.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	1000
Concentration of EG	0%, 25%, 50%, 85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.33 M
Reaction Volume (mL)	4

. As demonstrated in Figure 5a,b, CaCO₃ samples with an EG concentration of less than 50% tended to form calcite-like crystals, which was attributed to an overreaction. Conversely, increasing the EG concentration above 50% gradually suppressed the growth rate of CaCO₃, favoring the formation of complete vaterite structures. This is evident in particle size and distribution observed at higher EG concentrations, which were more favorable compared to those observed at 50% or lower, as shown in Figure 5c,d. The mean particle sizes at 50% and 85% EG concentrations were 1038 nm and 475 nm, respectively. Therefore, the optimal EG concentration was determined to be 85%.

3.3.4. Reaction Time

This step explored the effect of different reaction times on the formation of vaterite crystals, with operational parameters outlined in

Table 6. Parameters for reaction time experiment.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	1000
Concentration of EG	85%
Reaction Time (min)	5, 30, 60, 180, 1440
CaCl2/Na2CO3 (M)	1 M/0.1 M
Reaction Volume (mL)	4

. SEM analysis (Figure 6a–e) indicated that the optimal vaterite crystal phase and particle size distribution were achieved at a reaction time of 1 h (Figure 6c). It was observed that extending the reaction led to an increase in particle size. This increase might be attributed to the continuous formation of CaCO₃ at nucleation sites, facilitated by the interaction of Ca²⁺ and CO₃²⁻ ions. Notably, for reaction times shorter than one hour (Figure 6a,b), a clear presence of both calcite and larger vaterite particles was observed, with instances where calcite appeared embedded within vaterite. This suggests that the complete formation of vaterite might undergo a process of continuous decomposition and recrystallization, aligning with findings from Zhang et al. [46]. Therefore, a duration of 60 min was determined to be the optimal reaction time.

3.3.5. Initial Salt Concentration

Salt concentration affects the nucleation rate, which consequently influences the particle size. In this step, the effect of varying Na₂CO₃ concentrations on the particle size of CaCO₃ was examined, with operational parameters detailed in

Table 7. Parameters for initial salt concentration.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	1000
Concentration of EG	85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.05 M, 0.1 M, 0.33 M, 0.5 M, 1 M
Reaction Volume (mL)	4

. Results from Figure 7a–e indicate that the particle size of CaCO₃ increases together with a rise in the concentration of Na₂CO₃, presenting an opposite trend from the classic nucleation theory [47]. Notably, the smallest particle size was 344 nm at a Na₂CO₃ concentration of 0.05 M, aligning with the hypothesis proposed by Trushina et al. [40].

However, this study yielded CaCO₃ particles with an average size of 423 nm at 0.1 M Na₂CO₃, contrasting with findings from Trushina et al., who observed the smallest particles at 700 nm under similar conditions [40]. This phenomenon may be attributed to the interaction between the functional groups of EG and Ca²⁺ ions. The former, carrying opposite electrical charges, possibly facilitates the occupancy of Ca²⁺ ions at EG’s nucleation sites. Upon adding Na₂CO₃, the CO₃²⁻ ions were prompted to react with Ca²⁺ ions at these nucleation sites, leading to the formation of CaCO₃. Based on the experimental results, the optimal initial salt concentration was determined to be CaCl₂:Na₂CO₃ = 1 M:0.05 M.

3.3.6. Total Reaction Volume

This step investigated the impact of total reaction volumes on the particle size of CaCO₃, with operational parameters detailed in

Table 8. Parameters for total reaction volume experiment.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	1000
Concentration of EG	85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.1 M
Reaction Volume (mL)	4, 40, 120, 400

. Observations from Figure 8a–d reveal that the particle size of vaterite increased with the increment of reaction volume. Notably, the particle size of vaterite in a 400 mL solution reached 1002 nm. Moreover, the presence of calcite phase was observed in reactions conducted with 400 mL (Figure 8d). This phenomenon indicates that the total reaction volume has a noticeable impact not only on the particle size, but also on the crystal morphology of the products. Based on the experimental results, the optimal reaction volume was determined to be 4 mL for achieving the desired particle size and crystal structure.

3.4. Summary of Optimal Parameters for Drug Carrier Synthesis

The following table (

Table 9. Optimal parameters for CaCO₃ synthesis.

Factors	Parameters
Adding Order	CaCl2-first
Stirring Speed (rpm)	1150
Concentration of EG	85%
Reaction Time (min)	60
CaCl2/Na2CO3 (M)	1 M/0.05 M
Reaction Volume (mL)	4

) shows a series of optimal parameters identified from the experiments.

3.5. Drug Loading Simulation Experiment

The co-precipitation method was employed to synthesize calcium carbonate (CaCO₃) drug carriers, incorporating the fluorescently labeled drug TRITC-Dextran directly into the CaCO₃ synthesis process. The drug loading results of TRITC-Dextran (Figure 9b) shows that nearly all CaCO₃ particles emitted fluorescence signals, indicating effective drug incorporation into the carrier matrix. The results of the loading capacity (LC), which is calculated by Equation (4), reveal that the LC for the CaCO₃ drug carrier was 9.6 wt.%, compared with the LC of 10.3 wt.% achieved by Taman et al. [48] using liposomes for Gemcitabine (Gem) delivery. Typically, the LCs for liposome-based drug delivery systems range between 5 and 10 wt.%. In contrast, Donatan et al. [49], who utilized an adsorption method for loading TRITC-Dextran onto CaCO₃, reported an LC of less than 1 wt.%; similarly, Parakhonskiy et al. [6], employing the adsorption method, achieved a maximum LC of only 0.01 wt.%. These comparisons highlight the efficiency of the co-precipitation method and its promising capability for drug carrier fabrication using CaCO₃.

4. Conclusions

Compared to other calcium-rich biogenic wastes such as oyster and clam shells, coral remains at present to be a cleaner and more easily collected alternative. This study, initiated from a circular economy perspective, investigated the potential of repurposing coral remains, a topic typically associated with environmental challenges, into a valuable raw material for better use. The major composition of coral remains is CaCO₃, a common raw material in industrial and pharmaceutical products. In this study, coral remains could meet the industrial standards for CaCO₃ undergoing a series of purification and modification processes. Vaterite, one of the crystal phases of CaCO₃, demonstrated excellent physicochemical properties, making it a promising material for anticancer drug carriers. The conclusions drawn from the experiments are as follows:

• The composition analysis of coral remains showed the absence of heavy metals such as Pd and Cd, both of which are of most concern in food and pharmaceutical products, indicating their suitability as raw materials for these industries.
• The efficient conversion of CaCO₃ to CaO in an N₂ atmosphere at 800 °C within just 5 min demonstrates a significant enhancement in process efficiency, potentially reducing both time and cost.
• The whiteness level of purified CaCO₃ reached 95%, surpassing many industrial standards (93%), making it suitable for industrial applications.
• The synthesized vaterite possesses several desirable drug carrier properties such as spherical morphology, small particle size, high porosity, pH sensitivity, and biocompatibility. Given its widespread use in the food and pharmaceutical industries, CaCO₃ has shown to be a superior option for anticancer drug delivery compared to other drug carriers such as mesoporous silica nanoparticles and gold nanoparticles.
• The effective utilization of the EPR effect for targeting cancer cell necessitates particle sizes below 600 nm. Smaller particles are more efficient in penetrating cell membranes and also positively impact the drug loading capacity, a crucial factor of the efficiency of CaCO₃ as a drug carrier. While typical reproducibility of vaterite particle size range from 4 to 6 µm [40,50,51], our study successfully synthesized drug carriers with an average size of 344 nm, and some even smaller than 200 nm.
• During CaCO₃ synthesis, the involvement of EG necessitated sufficient time to form a complete vaterite crystal. Insufficient time resulted in the formation of either amorphous phases or incomplete calcite crystals.
• Given the high costs associated with cancer drug production and the expensive, intricately synthesized carriers typically used for their delivery, the overall price of anticancer drug carriers remains notably high. CaCO₃, in contrast, is a widely available, cost-effective, and stable material. Its application as a drug carrier could significantly reduce costs while maintaining excellent biocompatibility and precision in drug delivery. This approach not only provides a solution to the high expenses involved in synthesizing drug carriers, but also tackles environmental concerns related to coral remains, offering a dual advantage.