Anticancer activity of quantum size carbon dots: opportunities and challenges.

Research into the anticancer activity of quantum-sized carbon dots (CDs) has emerged as a promising avenue in cancer research. This CDs delves into the opportunities and challenges associated with harnessing the potential of these nanostructures for combating cancer. Quantum-sized carbon dots, owing to their unique physicochemical properties, exhibit distinct advantages as potential therapeutic agents. Opportunities lie in their tunable size, surface functionalization capabilities, and biocompatibility, enabling targeted drug delivery and imaging in cancer cells. However, we include challenges, a comprehensive understanding of the underlying mechanisms, potential toxicity concerns, and the optimization of synthesis methods for enhanced therapeutic efficacy. A succinct summary of the state of the research in this area is given in this review, emphasizing the exciting possibilities and ongoing challenges in utilizing quantum-sized carbon dots as a novel strategy for cancer treatment.

Carbon dots-facilitated on-demand dissolution of Ca-alginate hydrogel via site-specific mineralization for wound healing.

On-demand dissolution of hydrogels has shown much potential in easy and pain-free removal of wound dressings. This work firstly describes a type of carbon dots (CDs) for dissolving Ca-alginate hydrogel via site-specific mineralization method. The CDs were characterized by two features, which included presence of primary/secondary amine groups and generation of calcium crystals with Ca2+. Especially, the amount of primary/secondary amine groups on CDs played key role in determining whether hydrogel could be dissolved. When there were sufficient primary/secondary amine groups, the mineralization occurred on CDs rather than alginates due to the hydrogen bond between primary/secondary amine and carboxyl of alginates. Thereby, this promoted the gel-sol transition through Ca2+ capture from the hydrogels. Moreover, antibacterial test revealed Ca2+ capture from cell walls, while in vivo test revealed hypoxia relief due to porous structures of the renewed hydrogels. Overall, CDs with sufficient primary/secondary amine groups could dissolve Ca-alginate hydrogel through site-specific mineralization method, accompanying by additional functions of antibacterial and hypoxia relief.

Amine-Rich Carbon Dots Synthesized from Kappa-Carrageenan and l-Lysine as a Dual Probe for Detection of Folic Acid and Tumor-Targeted Delivery of Therapeutics.

Strategically designed, heteroatom-rich surface functionalized blue fluorescent carbon dots (CDs) were synthesized for high-throughput detection of folic acid (vitamin B9). The highly stable CDs could particularly detect vitamin B9 in the presence of 35 analytes, even up to 40 nM of the vitamin. The versatile CDs were found to have a high affinity for folic acid in wastewater, folic acid tablets, and food samples enriched with folic acid. The hemocompatibility of the CDs was also studied by using a hemolysis assay, confirming the CDs to be nontoxic to human blood samples up to 400 µg/mL. The CDs were then covalently conjugated to biotin, which possesses receptors that are overexpressed in tumor cells. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye) assay and confocal bioimaging studies proved the biotin-modified CDs (CDBT) were remarkably nontoxic in healthy cell lines (HEK-293) and highly target-specific toward tumor cells (HeLa), including triple-negative breast cancer cells (MDA-MB-231). The cytotoxicity assay of 5-fluorouracil encapsulated CDs (CDBTFu) showed the IC50 value to be 81 µM in HeLa cells and 185 µM in MDA-MB-231 cells, respectively, and significantly higher in HEK-293 cells (over 300 µM), owing to high specificity toward tumor cells.

Dual-Confinement and Surface-Ionization Induced Controllable Regulate Visible-Light-Activated Colorful Afterglow of Carbon Dots for Multifunctional Applications.

Low-energy visible-light-activated carbon dots (CDs)-based afterglow materials are difficult to realize due to the inherent aromatic carbon with high-energy absorption and the lack of effective regulation. Here, a new strategy for visible-light-activated CDs is proposed by combining dual-confinement and surface-ionization, which employs NaOH for additional confinement and surface ionization of CDs in a single boric acid (BA) matrix. The comparison experiments show that: i) shifting the excitation from UV-light to vis-light is realized by enhancing the low-energy surface states n→π* transition of the CDs by surface ionization of NaOH. ii) CDs are additionally protected by a more stable Na─O ionic bond after NaOH confinement, resulting in a brighter afterglow. iii) the energy gap (ΔEST) between the lowest singlet and triplet states is gradually shortened as increasing NaOH content, facilitating intersystem crossing, prolonging the lifetime of triplet excitons and efficiency. Further, vis-light-excited colorful afterglow powders are fabricated based on Förster Resonant Energy Transfer by combining the fluorescent dye 5-carboxytetramethylrhodamine. Finally, advanced white-light-activated time-resolved anti-counterfeiting and intelligent traffic flashing signs are realized. The work may shed new light on the design of low-energy-activated afterglow materials and broaden the application scenarios in the daily lives of human society.

Detection and adsorption of florfenicol in milk using bifunctional carbon dot-doped molecularly imprinted polymers.

Detection of florfenicol (FF) residues in animal-derived foods, as one of the most widely used antibiotics, is critically important to food safety. The fluorescent molecularly imprinted polymer (MIP) was synthesized by surface-initiated atom transfer radical polymerization technique with poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) microspheres, 4-vinylpyridine, ethylene glycol dimethacrylate, and FF as the matrix, functional monomer, crosslinker, and template molecule, respectively. Meanwhile, N-S co-doped carbon dot (CD) was synthesized with triammonium citrate and thiourea as precursors under microwave irradiation at 400 W for 2.5 min and then integrated into FF-MIP to obtain CD@FF-MIP. For comparison, non-imprinted polymer (NIP) without FF was also prepared. The adsorption capacity of CD@FF-MIP to FF reached 53.1 mg g-1, which was higher than that of FF-MIP (34.7 mg g-1), whereas the adsorption capacity of NIP was only 17.3 mg g-1. The adsorption equilibrium of three materials was reached within 50 min. Particularly, CD@FF-MIP exhibited an excellent fluorescence quenching response to FF in the concentration range of 3-50 µmol L-1. As a result, CD@FF-MIP was successfully utilized to extract FF in milk samples, which were analyzed by high-performance liquid chromatography. The standard recoveries were 95.8%-98.2%, and the relative standard deviation was 1.6%-4.2%. The method showed the advantages of simple operation, high sensitivity, excellent selectivity, and low cost, and also demonstrated a great application prospect in food detection.

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration.

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.

Utilizing Carbon Dots Derived from Waste Face Masks for Pentachlorophenol Detection.

Pentachlorophenol is a very toxic chemical that is used as a pesticide, fungicide, herbicide, wood preservative, etc., and it should be monitored in terms of human health and environmental production. Another environmental problem is the increase in the use of facemasks, especially during the COVID-19 pandemic. This study provides a value added chemicals to sustainability of recycling process. Fluorescent carbon dots (CDs) were synthesized from waste facemasks and investigated their fluorescence sensor performances. UV-Vis and fluorescence spectra of the synthesized carbon dots were recorded in different organic solvents. The sensor properties of these carbon dots against pesticides were investigated, and a 'turn-off' response was observed toward pentachlorophenol. The limit of detection was found 8.5 µM in the linear range from 43.3 µM to 375 µM. This study showed that waste plastics such as facemasks can be recycled to obtain carbon dots, which are used in different technological areas such as photocatalysis, bioimaging, etc., as well as in sensors.

Simultaneous detection of multiple microRNAs based on fluorescence resonance energy transfer under a single excitation wavelength.

MicroRNAs (miRNAs) play a key role in physiological processes, and their dysregulation is closely related to various human diseases. Simultaneous detection of multiple miRNAs is pivotal to cancer diagnosis at an early stage. However, most multicomponent analyses generally involve multiple excitation wavelengths, which are complicated and often challenging to simultaneously acquire multiple detection signals. In this study, a convenient and sensitive sensor was developed to simultaneously detection of multiple miRNAs under a single excitation wavelength through the fluorescence resonance energy transfer between the carbon dots (CDs)/quantum dots (QDs) and graphene oxide (GO). A hybridization chain reaction (HCR) was triggered by miRNA-141 and miRNA-21, resulting in the high sensitivity with a limit of detection (LOD) of 50 pM (3σ/k) for miRNA-141 and 60 pM (3σ/k) for miRNA-21. This simultaneous assay also showed excellent specificity discrimination against the mismatch. Furthermore, our proposed method successfully detected miRNA-21 and miRNA-141 in human serum samples at a same time, indicating its diagnostic potential in a clinical setting.

Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Radish residue carbon dots-based novel starch/chitosan film with high antioxidant, biocompatibility, and antibacterial activities for salmon fillets' active packaging.

The corruption of refrigerated marine fish results in global economic losses exceeding 25 billion euros annually. However, conventional preservatives present challenges, including singular functionality, potential toxicity, and high cost. In response, we developed multifunctional, safe, cost-effective, and environmentally friendly carbon dots derived from radish residues (R-CDs) by using the one-pot hydrothermal method. The surface of R-CDs is enriched with hydroxyl groups, conferring broad-spectrum antioxidant and antibacterial characteristics. R-CDs exhibited a notable 72.92 % inhibition rate on lipid peroxidation, surpassing the effectiveness of vitamin C (46 %). Additionally, R-CDs demonstrated impressive scavenging rates of 93.8 % for 2,2-diphenyl-1-picrylhydrazyl free radicals and 99.36 % for 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid-free radicals. In combating spoilage bacteria such as Aeromonas sobria and Hafnia alvei, R-CDs disrupted cell structures and influenced intracellular substance content. Importantly, co-cultivation with R-CDs showed no significant cytotoxicity. Further incorporating R-CDs into films using starch and chitosan (S/CS/R-CDs films) for efficient and convenient use in salmon fillets preservation. S/CS/R-CDs films effectively inhibited the growth of spoilage bacteria, lipid oxidation, and protein decomposition in salmon fillets, thereby extending shelf life by 4 days. This combination of antioxidant and antibacterial properties in R-CDs, along with the functional films, presents a promising approach for enhancing salmon fillet preservation.

Effect of carbon dot-doped Ti-MOF on CMC/Agar film and active packaging application on storage quality of fruits.

Ti-metal organic framework (Ti-MOF) doped with carbon dots (CDs) with enhanced antibacterial potential was synthesized using solvothermal-assisted mechanical stirring and used for the fabrication of CMC/Agar-based active packaging films. The incorporation of CD@Ti-MOF not only improved the tensile strength of the CMC/Agar film by 17.4% but also exhibited strong antioxidant activity with 100% of ABTS and 57.8% of DPPH radical scavenging using 0.64 cm2/mL of CMC/Agar/CD@Ti-MOF film. Furthermore, water vapor permeability, oxygen permeability, and ultraviolet light-blocking ability (95.7% of UV-B and 84.7% of UV-A) were improved significantly. The CMC/Agar/CD@Ti-MOF film showed strong antibacterial activity and could inhibit the progress of E. coli up to 8.2 Log CFU/mL and completely stopped the growth of L.monocytogenes after 12 h of incubation. Additionally, CMC/Agar/CD@Ti-MOF film extended the shelf life of cherry tomatoes preserved at 4 °C and delayed the quality degradation, maintaining the visual aspects of the packaging.

A novel bio-based fluorescent N, P-CDs@CMC/PEI composite hydrogel for sensitive detection and efficient capture of toxic heavy metal ions.

To address the serious environmental pollution problems of toxic heavy metal ions in water bodies, a novel fluorescent composite hydrogel N, P-CDs@CMC/PEI with a bio-based polymer matrix of carboxylmethyl cellulose (CMC), polyethylenimine (PEI) as a second interpenetrating network and N, P-doped carbon dots (N, P-CDs) as a fluorescent probe was prepared for simultaneous detection and capture of HMIs by a facile and simple one-step approach. The morphology, chemical structure, swelling ratio, mechanical strength and fluorescence property of these composite hydrogels were studied through varied characterization methods. The composite hydrogel showed sensitive and selective fluorescence response with Hg(II) and Fe(III) and the according LOD values were 0.48 and 0.27 mg L-1, respectively. The relationship between the types of the adsorbent, pH value, HMIs concentration and temperature on the adsorption capacity of these composite hydrogels were studied. The pseudo-second-order model and Langmuir model were applicable to explain the adsorption process of CPH2 for Hg(II) and Cr(VI). The maximum calculated adsorption capacities for the above targeted HMIs by Langmuir model were 846.7 and 289.5 mg g-1, respectively. Coexisting inorganic salts and organic acids in low concentration had little effects on Hg(II) and Cr(VI) removal and the composite hydrogel showed good recyclability and stability for Hg(II) and Cr(VI) removal after four cycles. The electrostatic attraction and coordination covalent bonds were responsible for the adsorption process.

Green-synthesized chitosan­carbon dot nanocomposite as turn-on aptasensor for detection and quantification of Leishmania infantum parasite.

Leishmania is one of the most common diseases between human and animals, caused by Leishmania infantum parasite. Here, we have developed an ultra-selective turn-on fluorescent probe based on an aptamer and Chitosan-CD nanocomposite. The CD used in this study were synthesized using Quercus cap extract and a microwave-assisted approach. The Chitosan-CD nanocomposite was optimized using several microscopic and spectroscopic techniques to possess a bright fluorescence emission before adding aptamer and totally quenched fluorescence after addition of aptamer. The designed probe was proficient in the detection and quantification Leishmania infantum parasite by selective targeting of poly(A) binding protein (PABP) on the surface of the parasite. The designed fluorescent biosensor with high sensitivity, excellent selectivity, and a limit of detection (LOD) of 94 cells/mL of the Leishmania infantum parasite as well as a linear response in the ranges of 188-750 cells/mL and 3000-6000 cells/mL (R2 ≥ 0.98 for both linear ranges). Additionally, the selectivity of the designed probe was evaluated in the presence of different pathogenic species such as Trypanosoma brucei parasite and Staphylococcus aureus bacteria, as well as LiIF2α and LiP2a and BSA proteins as interference substances. The results of this study shows that using Chitosan-CD nanocomposite is a great strategy for developing selective turn-on probes with extraordinary accuracy and sensitivity in identifying Leishmania infantum parasite, especially in the early stages of the disease, and it is promising for the future clinical applications.

Shining light on carbon dots: Toward enhanced antibacterial activity for biofilm disruption.

In spite of tremendous efforts dedicated to addressing bacterial infections and biofilm formation, the post-antibiotic ear continues to witness a gap between the established materials and an easily accessible yet biocompatible antibacterial reagent. Here we show carbon dots (CDs) synthesized via a single hydrothermal process can afford promising antibacterial activity that can be further enhanced by exposure to light. By using citric acid and polyethyleneimine as the precursors, the photoluminescence CDs can be produced within a one-pot, one-step hydrothermal reaction in only 2 h. The CDs demonstrate robust antibacterial properties against both Gram-positive and Gram-negative bacteria and, notably, a considerable enhancement of antibacterial effect can be observed upon photo-irradiation. Mechanistic insights reveal that the CDs generate singlet oxygen (1O2) when exposed to light, leading to an augmented reactive oxygen species level. The approach for disruption of biofilms and inhibition of biofilm formation by using the CDs has also been established. Our findings present a potential solution to combat antibacterial resistance and offer a path to reduce dependence on traditional antibiotics.

Confinement of Sustainable Carbon Dots Results in Long Afterglow Emitters and Photocatalyst for Radical Photopolymerization.

Sustainable carbon dots based on cellulose, particularly carboxymethyl cellulose carbon dots (CMCCDs), were confined in an inorganic network resulting in CMCCDs@SiO2. This resulted in a material exhibiting long afterglow covering a time frame of several seconds also under air. Temperature-dependent emission spectra gave information on thermally activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) while photocurrent experiments provided a deeper understanding of charge availability in the dark period, and therefore, its availability on the photocatalyst surface. The photo-ATRP initiator, ethyl α-bromophenylacetate (EBPA), quenched the emission from the millisecond to the nanosecond time frame indicating participation of the triplet state in photoinduced electron transfer (PET). Both free radical and controlled radical polymerization based on photo-ATRP protocol worked successfully. Metal-free photo-ATRP resulted in chain extendable macroinitiators based on a reductive mechanism with either MMA or in combination with styrene. Addition of 9 ppm Cu2+ resulted in Mw/Mn of 1.4 while an increase to 72 ppm improved uniformity of the polymers; that is Mw/Mn=1.03. Complementary experiments with kerria laca carbon dots confined materials, namely KCDs@SiO2, provided similar results. Deposition of Cu2+ (9 ppm) on the photocatalyst surface explains better uniformity of the polymers formed in the ATRP protocol.

Recent Progress in Folic Acid Detection Based on Fluorescent Carbon Dots as Sensors: A Review.

Folic acid (FA) is a water-soluble vitamin found in diverse natural sources and is crucial for preserving human health. The risk of health issues due to FA deficiency underscores the need for a straightforward and sensitive FA detection methodology. Carbon dots (CDs) have gained significant attention owing to their exceptional fluorescence performance, biocompatibility, and easy accessibility. Consequently, numerous research studies have concentrated on developing advanced CD fluorescent probes to enable swift and precise FA detection. Despite these efforts, there is still a requirement for a thorough overview of the efficient synthesis of CDs and their practical applications in FA detection to further promote the widespread use of CDs. This review paper focuses on the practical applications of CD sensors for FA detection. It begins with an in-depth introduction to FA and CDs. Following that, based on various synthetic approaches, the prepared CDs are classified into diverse detection methods, such as single sensing, visual detection, and electrochemical methods. Furthermore, persistent challenges and potential avenues are highlighted for future research to provide valuable insights into crafting effective CDs and detecting FA.

Organic-Inorganic Heterointerface-Expediting Electron Transfer Realizes Efficient Plasmonic Catalytic Sterilization via a Carbon-Dot Nanozyme.

Plasmonic nanozymes bring enticing prospects for catalytic sterilization by leveraging plasmon-engendered hot electrons. However, the interface between plasmons and nanozymes as the mandatory path of hot electrons receives little attention, and the mechanisms of plasmonic nanozymes still remain to be elucidated. Herein, a plasmonic carbon-dot nanozyme (FeCG) is developed by electrostatically assembling catalytic iron-doped carbon dots (Fe-CDs) with plasmonic gold nanorods. The energy harvesting and hot-electron migration are remarkably expedited by a spontaneous organic-inorganic heterointerface holding a Fermi level-induced interfacial electric field. The accumulated hot electrons are then fully utilized by conductive Fe-CDs to boost enzymatic catalysis toward overproduced reactive oxygen species. By synergizing with localized heating from hot-electron decay, FeCG achieves rapid and potent disinfection with an antibacterial efficiency of 99.6% on Escherichia coli within 5 min and is also effective (94.2%) against Staphylococcus aureus. Our work presents crucial insights into the organic-inorganic heterointerface in advanced plasmonic biocidal nanozymes.

Superoxide Dismutase-Mimetic Polyphenol-Based Carbon Dots for Multimodal Bioimaging and Treatment of Atopic Dermatitis.

Polyphenols have been investigated for their potential to mitigate inflammation in the context of atopic dermatitis (AD). In this study, epigallocatechin-3-gallate (EGCG)-based carbon dots (EGCG@CDs) were developed to enhance transdermal penetration, reduce inflammation, recapitulate superoxide dismutase (SOD) activity, and provide antimicrobial effects for AD treatment. The water-soluble EGCG@CDs in a few nanometers size exhibit a negative zeta potential, making them suitable for effective transdermal penetration. The fluorescence properties, including an upconversion effect, make EGCG@CDs suitable imaging probes for both in vitro and in vivo applications. By mimicking the SOD enzyme, EGCG@CDs scavenge reactive oxygen species (ROS) and actively produce hydrogen peroxide through a highly catalytic capability toward the oxygen reduction reaction, resulting in the inhibition of bacterial growth. The enhanced antioxidant properties, high charge mobility, and various functional groups of EGCG@CDs prove effective in reducing intracellular ROS in an in vitro AD model. In the mouse AD model, EGCG@CDs incorporated into a hydrogel actively penetrated the epidermal layer, leading to ROS scavenging, reduced mast cell activation, and histological recovery of skin barriers. This research represents the versatile potential of EGCG@CDs in addressing AD and advancing tissue engineering.

Chloramphenicol-imprinted polychitosan bounded with carbon dots as fluorescent sensor, dispersive sorbent, and drug carrier.

Chitosan, an abundant natural polysaccharide, was conjugated with carbon dots (CDs) and self-polymerized with chloramphenicol (CAP) templates to synthesize CD-incorporated and molecularly CAP-imprinted polychitosan (CD-MIC). The CD-MIC was used for fluorescent sensing, dispersive sorption, and dosage release of CAP at different pH levels. The sphere of action mechanism, approved by emission and excitation fluorescence, UV-Vis absorption, and fluorescence lifetime measurements, regulated the fluorescence static quenching. By the Perrin model, the quenching extent was linearly correlated to CAP within 0.17 - 33.2 µM (LOD = 37 nM) at pH 7.0. With an imprinting factor of 3.1, the CD-MIC was more selective for CAP than CD, although it was less sensitive to CAP. The recoveries of 5.0 µM CAP from milk matrix were 95% (RSD = 2.3%) for CD-MIC probes and 62% (RSD = 4.5%) for CD. The Langmuir and pseudo-second-order models preferably described the isothermal and kinetic sorptions of CAP into the imprinted cavities in CD-MICs, respectively. The Weber - Morris kinetic model showed three stages involved in intraparticle diffusion, which was pH-dependent and gradually arduous at the later stage, and showed external diffusion partly engaged in the diffusion mechanism. The 20 - 70% of CAP formulated in CAP-embedded CD-MICs were released in 8 - 48 h. The release percentage was lower at pH 7.0 than at pH 5.0 and 9.0, but the equilibrium time was shorter. At pH 7.0, the release percentage reached 45% at 10 min and slowly increased to 51% at 24 h.