Med Lasers 2023; 12(3): 133-146
Medical applications of stabilized ascorbic acid: a review of recent advances
Yehyun Kim1,2, Goeun Choi1,2,3
1Intelligent Nanohybrid Materials Laboratory (INML), Institute of Tissue Regeneration Engineering (ITREN), Dankook University, Cheonan, Republic of Korea
2Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan, Republic of Korea
3College of Science and Technology, Dankook University, Cheonan, Republic of Korea
Correspondence to: Goeun Choi
Received: September 8, 2023; Accepted: September 8, 2023; Published online: September 19, 2023.
© Korean Society for Laser Medicine and Surgery. All rights reserved.

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ascorbic acid (AA), also known as vitamin C, is a water-soluble nutrient that helps to maintain optimal physiological processes in the human body. It plays a role in collagen biosynthesis, photoprotection, free-radical scavenging, and enhancing immunity. However, because of its chemical instability, the AA needs to be protected from external environmental factors (including oxygen, moisture, and pH changes) to maintain its therapeutic efficacy. This review discusses advances reported over the past five years in stabilizing AA by loading it into carriers and highlights the medical applications of these stabilized formulations. Various carrier systems (such as liposomes, nanofibers, and hydrogels) have been developed to enhance the stability and facilitate the controlled release of AA. This paper reviews several such AA-loaded carriers and discusses their potential applicability in wound healing, skin treatment, bone regeneration, and cancer therapy. These innovative carrier systems could enable the effective and targeted delivery of AA in therapy, significantly improving patient outcomes.
Keywords: Ascorbic acid; Drug delivery system; Biological availability; Medical applications; Antioxidants

Ascorbic acid (AA), also known as vitamin C (IUPAC name, (5R)-5-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one; molecular formula, C6H8O6), is derived from a six-carbon sugar called L-threo-hex-2-enono-1,4-lactone, as shown in Fig. 1 [1-3]. Structurally similar to glucose, it comprises two interconvertible compounds: AA (a strong reducing agent) and its oxidized derivative L-dehydroascorbic acid (DHA) [4]. AA is an essential water-soluble nutrient that enables the maintenance of optimal physiological processes in the human body. Its activities include the promotion of collagen biosynthesis, reduction of melanin production, photoprotection, free-radical scavenging, and immunity enhancement, particularly against viral infections. Moreover, it helps prevent scurvy, aids in iron absorption to prevent anemia, and contributes to the treatment of common cold, cataracts, age-related muscular degeneration, cardiovascular diseases, and certain types of cancer [5,6]. Notably, AA consumption is vital for humans, primates, and other mammals that are unable to synthesize it owing to mutations in the gene that encodes the final enzyme in the AA-biosynthesis pathway (i.e., L-gulono-1,4-lactone oxidase) [1].

Figure 1. Molecular structure of ascorbic acid (IUPAC name, (5R)-5-[(1S)-1,2-Dihydroxyethyl]-3,4-dihydroxyfuran-2(5H)-one; molecular formula, C6H8O6) and its oxidation scheme (drawn by the authors).

AA deficiency is associated with the disease scurvy, which exhibits symptoms such as bleeding gums, slow wound healing, dry skin, muscle pain, and fatigue. Scurvy occurs when the synthesis of collagen, the primary protein in animal tissues, is impeded by low AA availability [3]. Currently, the recommended dietary allowance for AA is 90 and 75 mg/day for male and female, respectively. The daily consumption of an adequate quantity of fruits and vegetables leads to a steady-state concentration of AA (~80 µmol/L) in plasma; the oral intake of 1.25 g of AA can increase the AA concentration in plasma to 134.8 ± 20.6 µmol/L [7]. To maintain an optimal AA concentration within the body, the consumption of dietary supplements or AA-fortified foods along with naturally occurring fruits and vegetables is being increasingly favored by consumers [7].

Notably, on exposure to oxygen, moisture, light, alkaline pH, high temperature, and heavy-metal ions, AA undergoes a color change and degrades into biologically inactive compounds (such as oxalic acid) [8-10]. Owing to its antioxidant potency, AA undergoes rapid oxidation to DHA, irreversibly hydrolyzing into 2,3-L-diketogulonate under alkaline conditions (at high pH), which lacks the activity of AA [10,11]. Moreover, AA is prone to oxidation and decomposition in acidic environments (for example, in the stomach). Therefore, the delivery of intact AA (protected from gastric fluid) into the intestine can significantly enhance the therapeutic effects of dietary AA [12]. Loading AA into carriers can protect the active compound from degradation due to external conditions, enhancing the stability and shelf life of vitamin-based products [9,11].

Furthermore, AA plays a crucial role in various physiological functions, and stability enhancements could enable its application in different fields. This review discusses recent advances (reported over the past five years) in the stabilization of AA by carrier loading, highlighting the medical applications of these stabilized moieties. It could serve as a useful repository of information and facilitate future research on AA-loaded carriers.


Reactive oxygen species (ROS), produced as a result of normal physiological processes, are vital for cell signaling and tissue homeostasis [13]. However, these highly reactive species oxidize biological materials, exerting diverse effects on organisms. In animals, ROS are associated with cancer, aging, cataracts, Alzheimer’s disease, and blood-circulation disorders [14]. AA exhibits potent antioxidant properties, facilitating ROS detoxification [15]; its free-radical scavenging ability is attributed to the fully oxidized dehydroascorbate species generated from AA [16]. While AA primarily undergoes cycling between its fully reduced form and the monodehydroascorbate radical (A•–), complete oxidation process leading to DHA can indeed take place. A significant pathway involves the disproportionation of the A•–, wherein two A•– react to yield one molecule of ascorbate and one molecule of DHA. The rapid and essential disproportionation of the A•– plays a crucial role in the antioxidant properties exhibited by AA. This process effectively maintains the concentration of the A•– at an extremely low level, thus facilitating the oxidation of AA [16,17]. Notably, AA exhibits antioxidant properties that inhibit scar formation and skin damage, improving the functionality and moisture content of the skin barrier [18]. During inflammation, the immune system generates ROS to eliminate microorganisms. However, excessive ROS levels can adversely affect (and even kill) healthy host cells at the defect site (e.g., fibroblasts). Antioxidants minimize the negative impacts of ROS on healthy cells by activating cell-signaling pathways [19]. Furthermore, AA reduces the risk of cardiovascular disease by preventing the oxidation of low-density lipoproteins, a key factor in the development of atherosclerosis [20]. AA is also used as an antioxidant in the food industry [21]. The biological activity of AA in food (which includes the protection of oxidizable compounds, inhibition of enzymatic browning, oxygen scavenging, and prevention of nitrosamine formation) makes it a useful food additive [22].

Notably, AA exhibits both prooxidant and antioxidant properties [23]. It reduces transition-metal ions (such as Fe3+ and Cu3+) to generate highly reactive free radicals by the Fenton reaction, which cause DNA damage (by interacting with the phosphodiester backbone of DNA and modifying the DNA bases). The prooxidant activity of AA, which induces cytotoxicity, has been extensively explored for the prevention and treatment of cancer. Its efficacy is dose-dependent [24-26]. Low concentrations of AA (administered orally) exhibit antioxidant properties. Contrarily, high concentrations of AA (gram doses; administered intravenously) exhibit prooxidant properties, and can enhance the efficacy of certain cytostatic drugs (such as paclitaxel, carboplatin, and arsenic trioxide) and radiotherapy [27].

AA is a cofactor for enzymes and several bioactive processes associated with cellular functions (including neuromodulation, hormone regulation, immune-system support, and collagen synthesis) that enable the formation of connective tissue, bone matrix, and scar tissue during wound healing. As an enzyme cofactor, AA enables the regulation of hydroxylation in multiple enzymatic reactions [28,29]. AA is a cofactor for proline and lysine hydroxylases, which stabilize the tertiary structure of collagen molecules and promote collagen gene expression [30-32]. Moreover, AA contributes to all phases of the wound-healing process, accelerating healing in superficial and deep wounds across various body tissues (including the skin and bones). It facilitates neutrophil clearance during the inflammatory phase and supports collagen synthesis and maturation during the proliferative phase [31,32]. Notably, AA simultaneously increases the expression of genes related to osteogenesis (such as bone morphogenetic protein-2, osteocalcin, and RUNX2) and reduces the expression of those related to osteoclast differentiation (such as tartrate-resistant acid phosphatase, cathepsin K, receptor activator of nuclear factor kappa-B, and receptor activator of nuclear factor kappa-B ligand) [33]. Additionally, it upregulates endogenous retroviruses in lymphoma cells, inducing the viral defense pathway to activate the immune system and recognize tumor cells, thereby triggering interferon response [34]. Moreover, AA epigenetically modulates T-cells, promoting both innate and adaptive immune responses [35,36]. The activity of AA is schematically represented in Fig. 2.

Figure 2. Schematic representation of the activity of ascorbic acid (drawn by the authors).

Although AA is vital for several biochemical and metabolic processes, it is highly sensitive to environmental changes. Therefore, AA has been loaded into different types of carriers to protect it from external factors that adversely affect its stability [37-39].

AA-GCh-PCNC nanocapsules, comprising AA-encapsulated glycidyltrimethylammonium chloride (GTMAC)–chitosan (GCh) complexes (stabilized through electrostatic interactions) cross-linked with phosphorylated-cellulose nanocrystals (PCNC), exhibit a high encapsulation efficiency of 90.3% ± 0.42%. The synthesis of these nanocapsules is shown in Fig. 3A. AA-GCh-PCNCs exhibit the sustained and gradual release of AA, with an approximate cumulative release of 18% over 14 days. The release profiles of AA-GCh-PCNC under simulated human-digestive-system conditions (with pH 7.4 as the control) are shown in Figs. 3B, C; a significantly high cumulative release of AA over 8 hours is observed under these conditions. At 8 hours, ~27% of AA release occurs under digestive-system conditions, with less than 10% of AA release under control conditions (at neutral pH). The enhanced release of AA under digestive-system conditions can be attributed to the mucoadhesive properties of chitosan and cellulose nanocrystals, which facilitate the attachment of AA to the mucous membrane, enabling the controlled release of AA over an extended duration [11].

Figure 3. Modified cellulose nanocrystal/chitosan nanocapsules for the controlled release of ascorbic acid (AA). (A) Schematic illustration of the formation of AA-GCh-TPP and AA-GCh-PCNC nanocapsules from AA, chitosan (GCh), sodium tripolyphosphate (TPP), and phosphorylated-cellulose nanocrystals (PCNC). (B) Diagram of the human digestive system. (C) In-vitro simulation of digestive-system conditions to analyze the activity of AA-GCh-PCNC. Reused from the article of Baek et al. (Curr Res Food Sci 2021;4:215-23) [11] with original copyright holder’s permission.

Microencapsulation is widely used to maintain the stability of sensitive compounds under different conditions [29,40]. Kalaycioglu and Aydogan [41] reported microcapsule development by the layer-by-layer method for the dual drug delivery of AA and ibuprofen; the reported microcapsules comprise gold nanoparticles and solid lipid nanoparticles alternately coating the drug crystals, and chitosan was used as the final building block. Additionally, AA encapsulated by microcapsules comprising gelatin and gum arabic exhibit high stability. Thermogravimetric data indicates that pure AA exhibits two mass losses of 31.8% and 12.4% within the temperature ranges of 193°C-250°C and 275°C-311°C, respectively, whereas microencapsulated AA exhibits mass losses of 4% and ~85% in the temperature ranges of 168°C-218°C and 377°C-456°C. These results confirm that encapsulation significantly enhances the thermal stability of AA. Furthermore, after 15 days of storage, the concentration of free AA decreases to 15%, whereas the AA microcapsules exhibit a high retention rate of 90.3% [42].

Liposomes are structurally similar to cell membranes; moreover, they exhibit high biocompatibility, low toxicity, and low immunogenicity. Therefore, they effectively enhance the stability of bioactive compounds through encapsulation [10,43]. Jacob et al. [21] reported the development of stabilized fiber-reinforced-phospholipid-based powdered formulations of AA (Zeal-AA) using nanofiber (NF)-weaving (Zeal) technology that do not undergo rapid clearance from the bloodstream (unlike conventional liposomal formulations). The synthesis is shown in Fig. 4. Zeal-AA exhibits an encapsulation efficiency of 83.58% ± 2.18%. Moreover, the oral administration of Zeal-AA causes a 5.9-fold higher bioavailability of AA than that of pure AA. Several studies have evaluated the storage stability of AA-loaded liposomes [44,45]. According to Maione-Silva et al. [44], AA-loaded liposomes are stable for at least 30 days; after 30 days, samples stored at 4°C and 25°C retain ~95% and >90% of their initial AA content, respectively.

Figure 4. Schematic representation of the fabrication of phospholipid vesicles reinforced with turmeric fibers loaded with ascorbic acid. Reused from the article of Jacob et al. (ACS Omega 2021;6:5560-8) [21] with original copyright holder’s permission.

Electrospinning has emerged as a promising method for encapsulating bioactive molecules in the pharmaceutical field [46]. This technique enables the production of NFs with unique characteristics (such as a large surface-area-to-volume ratio, nanoscale structure, high porosity, and low molecular weight) [47,48]. Electrospinning has been used to incorporate a diverse range of drugs into NF webs/meshes, facilitating their application in pharmaceuticals. Khan et al. [49] reported the fabrication of AA-loaded NFs comprising hydroxypropyl-β-cyclodextrin (HP-β-CD). Thermogravimetric analysis indicates that the main degradation step of pure AA occurs within the temperature range of 190°C-220°C, whereas that of AA loaded in HP-β-CD-NF occurs within a wider temperature range (240°C-310°C). Moreover, the latter undergoes lower degradation than the former. Therefore, HP-β-CD improves the thermal stability of AA by protecting it from degradation. Avizheh et al. [50] reported the development of electrospun NFs incorporating AA and caffeine. The storage stability of AA in these NFs is greater than that of pure AA (the control). After 45 days of storage at room temperature, the control samples of AA exhibit a degradation rate of ~40%; contrarily, the NF formulations exhibit an AA content of ~80% after 45 days of storage at both room temperature and under refrigeration.

Furthermore, several studies have attempted to enhance the stability of AA by incorporating it into different types of carriers (such as scaffolds [32,51,52], hydrogels [5,26], NF molecular capsules [6], lipid nanocarriers [53], biopolymers [54], thin films/membranes [18], and water-in-oil-in-water emulsions [8]). Table 1 summarizes the stability of several AA-loaded carriers reported to date.

Table 1 . Stabilization of ascorbic acid on loading in different carriers

SystemMaterialStability improvementsReference
NanoparticlesGlycidyl trimethylammonium chloride, chitosan and phosphorylated-cellulose nanocrystalsShows sustained release of ascorbic acid over 14 days[11]
Tripolyphosphate-β-cyclodextrin and chitosanAfter 3 weeks of storage at 4°C, the retention of ascorbic acid is ~98.3%
Protection of ascorbic acid in acidic conditions, with sustained release in weakly alkaline conditions
Layered double hydroxide and tetraethyl orthosilicateDrug elimination range increases at high temperatures
Delays the release of ascorbic acid
MicroparticlesSodium alginate and gum arabicMaintains the stability of ascorbic acid up to 188°C[29]
Fully hydrogenated palm oil and palm oilGradually releases ascorbic acid[37]
Corn starch and gum arabicImproves the storage stability of ascorbic acid[39]
Gelatin, sodium caseinate and genipinShows controlled release of ascorbic acid[40]
Gold nanoparticles, solid lipid nanoparticles and chitosanShows controlled release of ascorbic acid[41]
Gelatin and gum arabicSignificantly improves the thermal stability of ascorbic acid
After 30 days of storage at 20°C, the retention of ascorbic acid is ~80%
Shows controlled release of ascorbic acid
LiposomesPhospholipids, cholesterol and phytosterolsEnhances the stability and controlled release of ascorbic acid[10]
Phospholipid and turmeric fibersExhibits 5.9 times more bioavailability than normal ascorbic acid
A single oral dose is capable of increasing the ascorbic acid levels in the body (relative to the control) for up to 24 hours
Yolk lecithin and cholesterolAfter 30 days of storage at 4°C and 25°C, the retention of ascorbic acid is ~80%[43]
Cholesterol, soybean phosphatidylcholine, 1,2-dioleoyl-3-trimethylammoniopropane and 1,2-distearoyl-sn-glycero-3-phospho-(1’-rac-glycerol)After 30 days of storage at 4°C and 25°C, the retention of ascorbic acid is >90%[44]
Cholesterol, Xanthan gum and Tween-80The average diameter changes negligibly on storage for 5 weeks at 4°C and 25°C[45]
NanofibersHydroxypropyl-β-cyclodextrinDrug elimination range increases at high temperatures[49]
Alginate and polyethylene oxideShows controlled release of ascorbic acid[46]
PVAAfter 45 days of storage at room temperature and under refrigeration, the retention of ascorbic acid is ~80%[50]
ScaffoldsPolycaprolactone and β-tricalcium phosphateShows prolonged and sustained release of ascorbic acid over 60 days[51]
Polylactic acid, polycaprolactone, and gelatinShows continuous release of ascorbic acid for 256 hours[32]
Poly(urethane-urea) and layered double hydroxidesShows sustained release of ascorbic acid for 5 days[52]
HydrogelsSalecan and chitosanProtects ascorbic acid from simulated gastric fluid
Maintains high levels of ascorbic acid in blood for 6 hours
Alkyl chainShows sustainable release of ascorbic acid in the presence of esterase[26]
Nanofiber-molecular capsulesPVA and β-CDLoading ascorbic acid into β-CD enables it to withstand heating up to 350°C
Exhibits programmable release profiles of ascorbic acid from the zeroth-order constant-release rate to the nonlinear burst, biphasic, and triphasic release profiles
Lipid nanocarrierTween® 20, 40, 60, and 80, stearic acid, and oleic acidExhibits controlled release of ascorbic acid[53]
BiopolymerGenipin and gelatinShows controlled release of ascorbic acid[54]
Thin film/membraneChitosan and agaroseShows controlled release of ascorbic acid[18]
W/O/W emulsionsGelatin, ethylenediaminetetraacetic acid disodium salt, polyglycerol polyricinoleate, hydrophobic fumed silica particles, β-CD, and Tween 80After 6 weeks of storage at 25°C, the retention of ascorbic acid is >80%
Shows controlled release of ascorbic acid

PVA, poly vinyl alcohol; β-CD, β-cyclodextrin.


Loading AA into carrier systems reduces its inherent instability, facilitating a diverse range of applications. This section discusses recent advances (over the past five years) in the medical application of stabilized AA, highlighting their significance.

AA is extensively used in wound healing owing to its capacity to promote fibroblast proliferation and stimulate collagen deposition during the re-epithelialization phase of wound repair [19]. Demir et al. [55] reported the development and characterization of novel regenerative, temporary, flexible wound dressings that can be easily applied to the skin and replaced after three days without causing damage to the wound. Xanthan/gelatin and keratin/xanthan/gelatin hydrogels (KXGHs) have been used in these wound dressings because of their high absorption capacity and ability to locally deliver AA. AA is continuously released from these hydrogels over 100 hours. Fibroblast viability analyses indicate that these AA-containing KXGHs exhibit cytocompatibility. Sirius red staining experiments indicate greater collagen synthesis in hydrogel-treated fibroblasts than in those of the control group.

Rezvani et al. [56] reported the development of vesicles loaded with AA and tocopherol (Eudragit® L100, Nutriose® FM06, and Lipoid S75). These vesicles protect the loaded drugs from intestinal oxidative-stress damage on oral administration, facilitating excellent intestinal-wound healing. The co-loaded vesicles show high biocompatibility, with >100% cell viability at different tested concentrations. The nutriosomes exhibit antioxidant properties, protect cells against oxidative stress, and promote cell proliferation with 110% viability. In-vitro studies indicate that neither the pure drug solutions nor liposomes effectively stimulate cell migration and proliferation for wound closure, whereas the nutriosomes and Eudragit® L100-nutriosomes accelerate the healing process. The nutriosomes enable complete wound closure within 96 hours, possibly owing to a synergistic effect of the antioxidants and Nutriose®.

Patients with diabetes often experience slow wound healing, which can lead to severe outcomes (such as limb amputation or death). Sun et al. [57] reported the development of novel epigallocatechin gallate (EGCG), AA, gelatin, and chitosan nanoparticles (EV NPS) that accelerate wound healing. Over a period of 2-8 days, diabetic mice administered EV NPS (comprising the EV NPS group) exhibit a significantly higher wound-healing rate than the model, no-load, and EGCG groups (all p < 0.001). Moreover, during the same period, the wound-healing rate of the model group is significantly different from that of the normal control group (with p < 0.05 and p < 0.001, respectively). These results indicate that EV NPS effectively promotes wound healing in diabetic mice, possibly because of increased collagen accumulation, which promotes angiogenesis and reduces inflammatory cell infiltration into the diabetic wounds.

In addition to the aforementioned treatments, diverse forms of AA have been extensively investigated for potential skin-related applications. Intact chitosan-AA-lactic acid composite membranes, enhanced by the addition of glycerol and polyethylene glycol (PEG), exhibit high potential for skin-tissue-engineering applications [31]. Skin patches comprising composite poly vinyl alcohol (PVA) NF-based molecular capsules exhibit the controlled and linear release of AA upon contact with skin moisture [6]. An adapalene-loaded transfersome gel incorporating AA has been proposed for the combination therapy of acne vulgaris [58]. AA-incorporated sodium alginate/polyethylene oxide species (fabricated in the core-shell and blended configurations using two distinct electrospinning setups) exhibit high potential as drug-delivery systems for the treatment of pigmented purpuric dermatosis [46].

Corneal stromal regeneration is challenging because of its complexity; moreover, there is a shortage of suitable donor corneas for transplantation. To resolve these issues, several studies have attempted to develop functional corneal stromal substrates. Moghanizadeh-Ashkezari et al. [52] reported a polymeric substrate comprising AA-loaded poly(urethane-urea)/ZnAl-layered double hydroxide-aligned scaffolds (PUU-AA-LDH), which mimics the extracellular matrix of the native corneal stroma tissue, facilitating tissue regeneration (Fig. 5A). According to in-vivo experimentation, the synthesized PUU shows biocompatibility in the rat model, with gradual degradation over time; it forms connective-tissue capsules and vessels around the sample with no evidence of complications (Fig. 5B). Histological analysis (with hematoxylin and eosin staining) 30 and 60 days after implantation indicates the formation of new blood vessels in the polymeric film. Moreover, the PUU-AA-LDH scaffold exhibits higher cell viability and keratocyte proliferation than other scaffolds, possibly owing to the presence of AA and zinc (Figs. 5C, D). Transcriptional and protein investigations indicate that the expression of vimentin, a major structural protein in normal keratocytes, is up-regulated in human keratocytes cultivated on PUU-AA-LDH, which exhibit a lower content of α-SMA than the control, indicating the differentiation of fewer cells into the myofibroblast phenotype (Figs. 5E, F). Therefore, the PUU-AA-LDH scaffold exhibits high potential as a substrate for the regeneration of corneal stromal tissue.

Figure 5. (A) Schematic representation of the synthesis of ascorbic acid-loaded poly(urethane-urea)/ZnAl-LDH aligned scaffolds. (B) Images of rats and PUU films stained with hematoxylin and eosin, 30 and 60 days after implantation. Black arrows indicate vessel formation in samples during the implantation period. (C) Cell viability results of PUU, PUU-LDH, and PUU-AA-LDH scaffolds according to the AlamarBlue assay after 24 hours and 1 week (*p < 0.05). (D) SEM images of keratocyte cell adhesion on the scaffolds after 24 hours and 1 week. (E) Immunocytochemistry of human corneal keratocytes for vimentin after 1 week of cultivation on PUU, PUU-LDH, and PUU-AA-LDH. Immune reactivity (green) of cells in all the groups to FITC-conjugated vimentin antibodies. (F) Percentage of human keratocytes that test positive for ALDH and α-SMA proteins, 24 hours and 1 week after cultivation in PUU, PUU-LDH, and PUU-AA-LDH. The graphs indicate a significantly higher percentage of ALDH protein expression by keratocytes cultivated for 24 hours and 1 week on PUU-AA-LDH than on PUU (p = 0.0001) or PUU-LDH (p = 0.0001). Notably, keratocytes cultivated on PUU-AA-LDH for 24 hours and 1 week exhibit a significantly lower percentage of α-SMA protein expression than those cultivated on PUU (p = 0.0001) or PUU-LDH (p = 0.041 after 24 hours and p = 0.003 after 1 week). Reused from the article of Moghanizadeh-Ashkezari et al. (ACS Appl Mater Interfaces 2019;11:35525-39) [52] with original copyright holder’s permission.

AA significantly influences bone formation by promoting osteoblast differentiation and inhibiting osteoclast differentiation; therefore, its incorporation into scaffolds could facilitate bone regeneration [32,51]. Hashemi et al. [32] reported the development of a highly porous three-dimensional scaffold comprising polylactic acid/polycaprolactone (PCL)/gelatin and AA for bone regeneration. In-vivo analysis indicates strong cell attachment to the pore walls of the scaffold; moreover, it confirms that AA-containing scaffolds exhibits better bone-healing properties than AA-free scaffolds. Bose et al. [51] reported enhanced bone regeneration using PCL-coated β-tricalcium phosphate (β-TCP) species containing AA. Microstructural analysis indicates a greater formation of multilayered osteoblast cells on the AA-incorporated sample surface compared with that on the control, consistent with 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. Moreover, the osteoblast cell viability increases two-fold in the presence of these AA-loaded species, regardless of the time. Additionally, the alkaline phosphatase (ALP) density increases on day 11, confirming the influence of AA on osteoblast differentiation. In-vitro osteosarcoma cell cultures show a four-fold decrease in cell proliferation on day 3 with the AA-loaded species compared with the control. Therefore, the sustained release of AA from PCL-coated TCP scaffolds effectively enhances osteoblast proliferation and differentiation, making it a promising drug-delivery system for bone-tissue engineering with minimal to no side effects.

Cano et al. [59] reported the synthesis of dual-loaded nanoparticles incorporating AA (with antioxidant and anti-inflammatory properties) and EGCG, which effectively reduce cognitive impairment in APPswe/PS1dE9 mice, a model of familial Alzheimer’s disease.

Research indicates that pharmacological concentrations of AA sensitize cancer cells to chemotherapeutic agents, enhancing their anticancer effects [60]. Synergistic interactions between AA and chemotherapeutics have been used for the treatment of several types of cancer (including breast cancer) [61,62]. Fahmy et al. [63] reported the development of a pH-responsive dual-loaded nanosystem (AA-OX/PEG-CS NPs) that uses PEGylated chitosan nanoparticles (PEG-CS NPs) to deliver both AA and oxaliplatin (OX) for breast-cancer treatment. This nanosystem exhibits significantly higher release rates of AA and OX in the acidic microenvironment of cancer cells (pH 5.5) than in the neutral microenvironment of healthy cells (pH 7.4) (Figs. 6A, B). After 72 hours at 37°C and pH 7.4, AA-OX/PEG-CS NPs release ~32.43% and 25.07% of AA and OX, respectively, whereas they release ~83.2% and 90% of AA and OX, respectively, at pH 5.5 (keeping all other conditions constant). MTT assays analyzing the effectiveness of AA and OX in reducing cell viability indicate that the IC50 value of AA alone is 150.8 ± 26.5 µg/ml (Fig. 6C), whereas that of AA encapsulated in CS NPs is IC50 44.87 ± 11.49 µg/ml (Fig. 6D). Additionally, systems comprising AA and OX individually encapsulated in PEG-CS NPs exhibit excellent reductions in cellular viability, with IC50 values of 23.3 ± 3.73 and 17.98 ± 3.99 µg/ml, respectively (Fig. 6E). Testing the combination of AA and OX in both CS and CS-PEG NPs on MCF-7 cells indicates that AA-OX/CS NPs exhibit an IC50 of 18.69 ± 2.22 µg/ml, while AA-OX/CS-PEG NPs show the lowest IC50 value (7.50 ± 0.69 µg/ml) (Figs. 6F, G). Therefore, PEGylated CS NPs loaded with AA and OX (individually and in combination) exhibit high potential for breast-cancer treatment. The medical applications of AA-loaded carriers are summarized in Table 2.

Table 2 . Medical applications of ascorbic-acid-loaded carriers

Wound healingThin film/membraneChitosan and agaroseAscorbic acidIn vitro[18]
MembranesBacterial cellulose and pullulanAscorbic acid and vitamin EIn vitro[19]
NanofibersPoly vinyl alcoholAscorbic acid and caffeineIn vitro and in vivo[50]
HydrogelsKeratin, xanthan, and gelatinAscorbic acidIn vitro[55]
Intestinal wound healingLiposomesS75 phospholipid, Nutriose® FM06, and Eudragit® L100Ascorbic acid and tocopherolIn vitro[56]
Diabetic wound healingNanoparticlesGelatin and chitosanAscorbic acid and epigallocatechin gallateIn vivo[57]
Skin tissue engineeringMembranesChitosan, lactic acid, glycerol and polyethylene glycolAscorbic acidIn vitro[31]
Skin patchNanofiber-molecular capsulesPoly vinyl alcohol and β-cyclodextrinAscorbic acidIn vitro[6]
Acne Vulgaris treatmentMembranesTransfersomeAscorbic acid and adapaleneIn vitro and in vivo[58]
Pigmented purpuric dermatosis treatmentNanofibersAlginate and polyethylene oxideAscorbic acidIn vitro[46]
Corneal stromal tissue regenerationScaffoldsPoly(urethane-urea) and layered double hydroxideAscorbic acid and zincIn vitro and in vivo[52]
Bone regenerationScaffoldsPolylactic acid, polycaprolactone, and gelatinAscorbic acidIn vitro and in vivo[32]
ScaffoldsPolycaprolactone and β-tricalcium phosphateAscorbic acidIn vitro[51]
Alzheimer’s diseaseNanoparticlesPoly(lactic-co-glycolic acid) and polyethylene glycolAscorbic acid and epigallocatechin-3-gallateIn vitro and in vivo[59]
Breast cancer treatmentNanoparticlesPolyethylene glycol and chitosanAscorbic acid and oxaliplatinIn vitro[63]
Cancer immunotherapyHydrogelsAlkyl chainAscorbic acid and interferon genes (STING) agonist-4 (SA)In vitro, ex vivo, and in vivo[26]

Figure 6. Time-dependent release profiles of ascorbic acid (AA) from (A) AA/PEG-CS NPs and (B) AA-OX/PEG-CS NPs at 37℃ and pH 7.4 and 5.5. Concentration-dependent effects of the tested compounds on the cellular viability of MCF-7 cells. MCF-7 cells treated with increasing concentrations (0.625, 1.25, 2.5, 5, 10, 20, 40, 80, 160, and 320 μg/ml) of (C) AA, (D) AA/CS NPs, (E) AA/PEG-CS NPs, (F) AA-OX/CS NPs, and (G) AA-OX/PEG-CS NPs for 48 hours. Their cellular viability is measured using the MTT assay (in triplicates). Relative IC50 values are commonly reported in pharmacological studies. Moreover, the curve-fitting approach considers the maximal and minimal responses (not simply the values between two adjacent concentrations). Reused from the article of Fahmy et al. (Pharmaceutics 2022;14:407) [63] with original copyright holder’s permission.

AA, a powerful antioxidant and essential water-soluble nutrient, enables the maintenance of optimal physiological processes in the human body. It exhibits several useful activities in the body; for example, it promotes collagen biosynthesis, scavenges free radicals, and boosts immunity against viral infections. However, AA is chemically unstable and prone to degradation, particularly on exposure to oxygen, moisture, light, high temperatures, and alkaline/acidic environments. To increase the stability of AA and facilitate its widespread application, several studies have investigated the loading of AA into carriers.

This review highlights recent advances in AA stabilization through carrier loading. Various carrier systems (including nanocapsules, microcapsules, liposomes, and NFs) have been used for the effective protection and delivery of AA. In summary, the loading of AA into carriers could open new frontiers in the medical utilization of AA. Carrier systems simultaneously protect AA from degradation, enhance its effectiveness, and promote its controlled delivery to specific target sites. AA-loaded carriers exhibit high potential for advanced wound healing, skin-related therapies, bone regeneration, and cancer treatment. Further research in this field could enable the development of highly efficient medical treatments and therapies that utilize the full potential of AA.






Conceptualization: GC. Data curation: all authors. Formal analysis: all authors. Funding acquisition: GC. Investigation: GC. Methodology: all authors. Project administration: GC. Visualization: all authors. Writing–original draft: all authors. Writing–review & editing: all authors.


No potential conflict of interest relevant to this article was reported.


This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2022R1F1A1076459) and the research fund of Dankook University Research and Business Development Foundation in 2023.



  1. Cruz-Rus E, Amaya I, Valpuesta V. The challenge of increasing vitamin C content in plant foods. Biotechnol J 2012;7:1110-21.
    Pubmed CrossRef
  2. Kietzmann T. Vitamin C: from nutrition to oxygen sensing and epigenetics. Redox Biol 2023;63:102753.
    Pubmed KoreaMed CrossRef
  3. Abbas S, Da Wei C, Hayat K, Xiaoming Z. Ascorbic acid: microencapsulation techniques and trends-a review. Food Rev Int 2012;28:343-74.
  4. Adikwu E, Deo O. Hepatoprotective effect of vitamin C (ascorbic acid). Pharmacol Pharm 2013;4:84-92.
  5. Hu X, Wang Y, Zhang L, Xu M. Formation of self-assembled polyelectrolyte complex hydrogel derived from salecan and chitosan for sustained release of vitamin C. Carbohydr Polym 2020;234:115920.
    Pubmed CrossRef
  6. Calzado-Delgado M, Guerrero-Pérez MO, Yeung KL. Dissolvable topical formulations for burst and constant delivery of vitamin C. ACS Omega 2023;8:12636-43.
    Pubmed KoreaMed CrossRef
  7. Yin X, Chen K, Cheng H, Chen X, Feng S, Song Y, et al. Chemical stability of ascorbic acid integrated into commercial products: a review on bioactivity and delivery technology. Antioxidants (Basel) 2022;11:153.
    Pubmed KoreaMed CrossRef
  8. Wang Q, Zhu X, Shi F, Liu Y, Hu W, Yang Z. Influence of β-cyclodextrin concentration on the physicochemical properties and skin permeation behavior of vitamin C-loaded Pickering water-in-oil-in-water (W1/O/W2) double emulsions. J Drug Deliv Sci Technol 2022;72:103368.
  9. Comunian T, Babazadeh A, Rehman A, Shaddel R, Akbari-Alavijeh S, Boostani S, et al. Protection and controlled release of vitamin C by different micro/nanocarriers. Crit Rev Food Sci Nutr 2022;62:3301-22.
    Pubmed CrossRef
  10. Amiri S, Rezazadeh-Bari M, Alizadeh-Khaledabad M, Amiri S. New formulation of vitamin C encapsulation by nanoliposomes: production and evaluation of particle size, stability and control release. Food Sci Biotechnol 2018;28:423-32.
    Pubmed KoreaMed CrossRef
  11. Baek J, Ramasamy M, Willis NC, Kim DS, Anderson WA, Tam KC. Encapsulation and controlled release of vitamin C in modified cellulose nanocrystal/chitosan nanocapsules. Curr Res Food Sci 2021;4:215-23.
    Pubmed KoreaMed CrossRef
  12. Kameshima Y, Sasaki H, Isobe T, Nakajima A, Okada K. Synthesis of composites of sodium oleate/Mg-Al-ascorbic acid-layered double hydroxides for drug delivery applications. Int J Pharm 2009;381:34-9.
    Pubmed CrossRef
  13. Su LJ, Zhang JH, Gomez H, Murugan R, Hong X, Xu D, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis. Oxid Med Cell Longev 2019;2019:5080843.
    Pubmed KoreaMed CrossRef
  14. Nagata T, Todoriki S, Masumizu T, Suda I, Furuta S, Du Z, et al. Levels of active oxygen species are controlled by ascorbic acid and anthocyanin in Arabidopsis. J Agric Food Chem 2003;51:2992-9.
    Pubmed CrossRef
  15. Wu SY, Hou LL, Zhu J, Wang YC, Zheng YL, Hou JQ, et al. Ascorbic acid-mediated reactive oxygen species homeostasis modulates the switch from tapetal cell division to cell differentiation in Arabidopsis. Plant Cell 2023;35:1474-95.
    Pubmed KoreaMed CrossRef
  16. Njus D, Kelley PM, Tu YJ, Schlegel HB. Ascorbic acid: the chemistry underlying its antioxidant properties. Free Radic Biol Med 2020;159:37-43.
    Pubmed CrossRef
  17. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta 2012;1826:443-57.
    Pubmed KoreaMed CrossRef
  18. Vivcharenko V, Wojcik M, Palka K, Przekora A. Highly porous and superabsorbent biomaterial made of marine-derived polysaccharides and ascorbic acid as an optimal dressing for exuding wound management. Materials (Basel) 2021;14:1211.
    Pubmed KoreaMed CrossRef
  19. Atila D, Karataş A, Keskin D, Tezcaner A. Pullulan hydrogel-immobilized bacterial cellulose membranes with dual-release of vitamin C and E for wound dressing applications. Int J Biol Macromol 2022;218:760-74.
    Pubmed CrossRef
  20. Moser MA, Chun OK. Vitamin C and heart health: a review based on findings from epidemiologic studies. Int J Mol Sci 2016;17:1328.
    Pubmed KoreaMed CrossRef
  21. Jacob J, Sukumaran NP, Jude S. Fiber-reinforced-phospholipid vehicle-based delivery of l-ascorbic acid: development, characterization, ADMET profiling, and efficacy by a randomized, single-dose, crossover oral bioavailability study. ACS Omega 2021;6:5560-8.
    Pubmed KoreaMed CrossRef
  22. Gopi S, Balakrishnan P. Evaluation and clinical comparison studies on liposomal and non-liposomal ascorbic acid (vitamin C) and their enhanced bioavailability. J Liposome Res 2021;31:356-64.
    Pubmed CrossRef
  23. Chen G, Chang TMS. Dual effects include antioxidant and pro-oxidation of ascorbic acid on the redox properties of bovine hemoglobin. Artif Cells Nanomed Biotechnol 2018;46(sup2):983-92.
    Pubmed CrossRef
  24. Osiecki M, Ghanavi P, Atkinson K, Nielsen LK, Doran MR. The ascorbic acid paradox. Biochem Biophys Res Commun 2010;400:466-70.
    Pubmed CrossRef
  25. Putchala MC, Ramani P, Sherlin HJ, Premkumar P, Natesan A. Ascorbic acid and its pro-oxidant activity as a therapy for tumours of oral cavity -- a systematic review. Arch Oral Biol 2013;58:563-74.
    Pubmed CrossRef
  26. Zhang H, Liu K, Gong Y, Zhu W, Zhu J, Pan F, et al. Vitamin C supramolecular hydrogel for enhanced cancer immunotherapy. Biomaterials 2022;287:121673.
    Pubmed CrossRef
  27. Cimmino L, Neel BG, Aifantis I. Vitamin C in stem cell reprogramming and cancer. Trends Cell Biol 2018;28:698-708.
    Pubmed KoreaMed CrossRef
  28. Hu Y, Mo G, Wang Y, Guo J, Huang C. Fabrication and characterization of TPP-β-cyclodextrin/chitosan supramolecular nanoparticles for delivery dual bioactive compounds. J Mol Liq 2021;343:117650.
  29. Barra PA, Márquez K, Gil-Castell O, Mujica J, Ribes-Greus A, Faccini M. Spray-drying performance and thermal stability of L-ascorbic acid microencapsulated with sodium alginate and gum arabic. Molecules 2019;24:2872.
    Pubmed KoreaMed CrossRef
  30. Pullar JM, Carr AC, Vissers MCM. The roles of vitamin C in skin health. Nutrients 2017;9:866.
    Pubmed KoreaMed CrossRef
  31. Madni A, Khan R, Ikram M, Naz SS, Khan T, Wahid F. Fabrication and characterization of chitosan-vitamin C-lactic acid composite membrane for potential skin tissue engineering. Int J Polym Sci 2019;2019:4362395.
  32. Hashemi SF, Mehrabi M, Ehterami A, Gharravi AM, Bitaraf FS, Salehi M. In-vitro and in-vivo studies of PLA /PCL /gelatin composite scaffold containing ascorbic acid for bone regeneration. J Drug Deliv Sci Technol 2021;61:102077.
  33. Choi HK, Kim GJ, Yoo HS, Song DH, Chung KH, Lee KJ, et al. Vitamin C activates osteoblastogenesis and inhibits osteoclastogenesis via Wnt/β-catenin/ATF4 signaling pathways. Nutrients 2019;11:506.
    Pubmed KoreaMed CrossRef
  34. Liu M, Ohtani H, Zhou W, Ørskov AD, Charlet J, Zhang YW, et al. Vitamin C increases viral mimicry induced by 5-aza-2'-deoxycytidine. Proc Natl Acad Sci U S A 2016;113:10238-44.
    Pubmed KoreaMed CrossRef
  35. Sasidharan Nair V, Song MH, Oh KI. Vitamin C facilitates demethylation of the Foxp3 enhancer in a Tet-dependent manner. J Immunol 2016;196:2119-31.
    Pubmed CrossRef
  36. Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, et al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell 2015;162:974-86. Erratum in: Cell 2016;164:1073. Erratum in: Cell 2017;169:361.
    Pubmed KoreaMed CrossRef
  37. dos Santos Carvalho JD, Oriani VB, de Oliveira GM, Hubinger MD. Characterization of ascorbic acid microencapsulated by the spray chilling technique using palm oil and fully hydrogenated palm oil. LWT 2019;101:306-14.
  38. Yasaei M, Khakbiz M, Zamanian A, Ghasemi E. Synthesis and characterization of Zn/Al-LDH@SiO2 nanohybrid: intercalation and release behavior of vitamin C. Mater Sci Eng C Mater Biol Appl 2019;103:109816.
    Pubmed CrossRef
  39. Leyva-López R, Palma-Rodríguez HM, López-Torres A, Capataz-Tafur J, Bello-Pérez LA, Vargas-Torres A. Use of enzymatically modified starch in the microencapsulation of ascorbic acid: Microcapsule characterization, release behavior and in vitro digestion. Food Hydrocoll 2019;96:259-66.
  40. Fraj J, Petrović L, Đekić L, Budinčić JM, Bučko S, Katona J. Encapsulation and release of vitamin C in double W/O/W emulsions followed by complex coacervation in gelatin-sodium caseinate system. J Food Eng 2021;292:110353.
  41. Kalaycioglu GD, Aydogan N. Layer-by-layer coated microcapsules with lipid nanodomains for dual-drug delivery. Colloids Surf A Physicochem Eng Asp 2020;584:124037.
  42. da Cruz MCR, Dagostin JLA, Perussello CA, Masson ML. Assessment of physicochemical characteristics, thermal stability and release profile of ascorbic acid microcapsules obtained by complex coacervation. Food Hydrocoll 2019;87:71-82.
  43. Liu X, Wang P, Zou YX, Luo ZG, Tamer TM. Co-encapsulation of vitamin C and β-Carotene in liposomes: storage stability, antioxidant activity, and in vitro gastrointestinal digestion. Food Res Int 2020;136:109587.
    Pubmed CrossRef
  44. Maione-Silva L, de Castro EG, Nascimento TL, Cintra ER, Moreira LC, Cintra BAS, et al. Ascorbic acid encapsulated into negatively charged liposomes exhibits increased skin permeation, retention and enhances collagen synthesis by fibroblasts. Sci Rep 2019;9:522.
    Pubmed KoreaMed CrossRef
  45. Lv X, Wu Z, Qi X. High skin permeation, deposition and whitening activity achieved by xanthan gum string vitamin c flexible liposomes for external application. Int J Pharm 2022;628:122290.
    Pubmed CrossRef
  46. Rezaei S, Valipouri A, Hosseini Ravandi SA, Kouhi M, Ghasemi Mobarakeh L. Fabrication, characterization, and drug release study of vitamin C-loaded alginate/polyethylene oxide nanofibers for the treatment of a skin disorder. Polym Adv Technol 2019;30:2447-57.
  47. Xue J, Wu T, Dai Y, Xia Y. Electrospinning and electrospun nanofibers: methods, materials, and applications. Chem Rev 2019;119:5298-415.
    Pubmed KoreaMed CrossRef
  48. Wang XX, Yu GF, Zhang J, Yu M, Ramakrishna S, Long YZ. Conductive polymer ultrafine fibers via electrospinning: preparation, physical properties and applications. Prog Mater Sci 2021;115:100704.
  49. Khan N, Singh AK, Saneja A. Preparation, characterization, and antioxidant activity of L-ascorbic acid/HP-β-cyclodextrin inclusion complex-incorporated electrospun nanofibers. Foods 2023;12:1363.
    Pubmed KoreaMed CrossRef
  50. Avizheh L, Peirouvi T, Diba K, Fathi-Azarbayjani A. Electrospun wound dressing as a promising tool for the therapeutic delivery of ascorbic acid and caffeine. Ther Deliv 2019;10:757-67.
    Pubmed CrossRef
  51. Bose S, Sarkar N, Vahabzadeh S. Sustained release of vitamin C from PCL coated TCP induces proliferation and differentiation of osteoblast cells and suppresses osteosarcoma cell growth. Mater Sci Eng C Mater Biol Appl 2019;105:110096.
    Pubmed KoreaMed CrossRef
  52. Moghanizadeh-Ashkezari M, Shokrollahi P, Zandi M, Shokrolahi F, Daliri MJ, Kanavi MR, et al. Vitamin C loaded poly(urethane-urea)/ZnAl-LDH aligned scaffolds increase proliferation of corneal keratocytes and up-regulate vimentin secretion. ACS Appl Mater Interfaces 2019;11:35525-39.
    Pubmed CrossRef
  53. Eh Suk VR, Mohd Latif F, Teo YY, Misran M. Development of nanostructured lipid carrier (NLC) assisted with polysorbate nonionic surfactants as a carrier for l-ascorbic acid and Gold Tri.E 30. J Food Sci Technol 2020;57:3259-66.
    Pubmed KoreaMed CrossRef
  54. Whitehead FA, Paramita VD, Teimouri S, Young S, Kasapis S. Controlled release of ascorbic acid from genipin-crosslinked gelatin matrices under moving boundary conditions. Food Hydrocoll 2019;89:171-9.
  55. Demir GC, Erdemli Ö, Keskin D, Tezcaner A. Xanthan-gelatin and xanthan-gelatin-keratin wound dressings for local delivery of Vitamin C. Int J Pharm 2022;614:121436.
    Pubmed CrossRef
  56. Rezvani M, Manca ML, Caddeo C, Escribano-Ferrer E, Carbone C, Peris JE, et al. Co-loading of ascorbic acid and tocopherol in Eudragit-nutriosomes to counteract intestinal oxidative stress. Pharmaceutics 2019;11:13.
    Pubmed KoreaMed CrossRef
  57. Sun M, Xie Q, Cai X, Liu Z, Wang Y, Dong X, et al. Preparation and characterization of epigallocatechin gallate, ascorbic acid, gelatin, chitosan nanoparticles and their beneficial effect on wound healing of diabetic mice. Int J Biol Macromol 2020;148:777-84.
    Pubmed CrossRef
  58. Vasanth S, Dubey A, Ravi GS, Lewis SA, Ghate VM, El-Zahaby SA, et al. Development and investigation of vitamin C-enriched adapalene-loaded transfersome gel: a collegial approach for the treatment of acne vulgaris. AAPS PharmSciTech 2020;21:61.
    Pubmed CrossRef
  59. Cano A, Ettcheto M, Chang JH, Barroso E, Espina M, Kühne BA, et al. Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer's disease mice model. J Control Release 2019;301:62-75.
    Pubmed KoreaMed CrossRef
  60. Pires AS, Marques CR, Encarnação JC, Abrantes AM, Marques IA, Laranjo M, et al. Ascorbic acid chemosensitizes colorectal cancer cells and synergistically inhibits tumor growth. Front Physiol 2018;9:911.
    Pubmed KoreaMed CrossRef
  61. Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996;103:183-9.
    Pubmed CrossRef
  62. Wu CW, Liu HC, Yu YL, Hung YT, Wei CW, Yiang GT. Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways. Oncol Rep 2017;37:2177-84.
    Pubmed CrossRef
  63. Fahmy SA, Ramzy A, Mandour AA, Nasr S, Abdelnaser A, Bakowsky U, et al. PEGylated chitosan nanoparticles encapsulating ascorbic acid and oxaliplatin exhibit dramatic apoptotic effects against breast cancer cells. Pharmaceutics 2022;14:407.
    Pubmed KoreaMed CrossRef

This Article

Cited By Articles
  • CrossRef (0)
  • Download (90)

Author ORCID Information

Funding Information


Social Network Service