Ascorbic Acid Delivery Research Articles

Vitamin C and its derivatives in maintaining the good skin condition

Vitamin C is one of the most important and necessary nutrient for human health, which has great potential as cosmeceutic, which protects health and the skin good condition. Thru the collagen biosynthesis stimulation it affects to the physiology of human skin, participating in the hydroxylation process of proline and lysine, and participates in tissue reconstruction while wound healing. Deficiency of vitamin C causes irregularities in the blood vessels functioning, epidermis and dermis. Is an effective antioxidant neutralizing free radicals, prevents inflammatory and carcinogenic processes. The epidermis and dermis are most exposed to free radicals from the external environment and from the inside of the body. In inflammatory diseases of the skin, such as atopic dermatitis, psoriasis, in the proper skin the levels of vitamin C are reduced. Therefore, delivering it to the skin using cosmetic preparations is important not only for cosmetic, but also health effect. The problem associated with the introduction of vitamin C in cosmetics is its limited penetration through the stratum corneum. Current studies are focused on searching for stable compounds of ascorbic acid and new media, which will allow for better way of delivery of ascorbic acid to the dermis in the future.

Formulation of Ascorbic Acid and Betaine-based Therapeutic Deep Eutectic System for Enhanced Transdermal Delivery of Ascorbic Acid.

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.

Ascorbic acid-loaded gellan-g-poly(ethylene glycol) methacrylate matrix as a wound-healing material

Ascorbic acid (AA) is one of the important biomolecules involved in all phases of wound healing. The aim of this study was to develop a new hydrogel system that offers topical delivery of ascorbic acid to wounds during wound care management. In this work, we grafted poly (ethylene glycol) methacrylate onto a renewable biopolymer gellan, and the graft copolymer (GPMA) formed was crosslinked covalently and ionically, and used as a matrix for delivering AA to the wounds. By the processes of grafting and crosslinking, the mechanical properties of the gellan increased several fold compared to mechanically weak native gellan. In vitro cytotoxicity evaluation showed that GPMA was non-cytotoxic to fibroblast cells. GPMA hydrogel matrix allowed the sustained release of AA. When AA was incorporated in GPMA, a significant improvement in wound closure was observed in scratch wound assay performed with keratinocytes. Since AA acts as a cofactor in collagen synthesis, the controlled delivery of AA to the wound microenvironment favors the up-regulation of colα1 gene expression. This study revealed that ascorbic acid, at a concentration of 150 μM, has a favorable impact on wound healing when tested in vitro. Overall results indicate that the GPMA matrix could be a promising material for wound healing applications.

Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Neutral Oil-Incorporated Liposomal Nanocarrier for Increased Skin Delivery of Ascorbic Acid

In this study, a neutral oil-incorporated liposomal system (lipo-oil-some, LOS) was designed to improve the skin absorption of ascorbic acid (Vit C), and the effects of an edge activator and neutral oil on the skin absorption of Vit C were evaluated. As components of the LOS system, sodium deoxycholate, polysorbate 80, and cholesterol were screened as edge activators, and camellia oil, tricaprylin, and grapeseed oil were employed as neutral oils. The LOS systems prepared by the ethanol injection method were spherical in shape, 130-350 nm in size, and had 4-27% Vit C loading efficiency (%). In a skin absorption study using a Franz diffusion cell mounted with porcine skin, the LOS system prepared with sodium deoxycholate (10 w/w% of phospholipid) exhibited 1.2-and 2.9-fold higher absorption than those prepared with polysorbate 80 and cholesterol, respectively. Moreover, the type of neutral oil had a marked effect on the absorption of Vit C; the liposomal system containing camellia oil provided 1.3 to 1.8 times higher flux (45.4 μg/cm2∙h) than vesicles with tricaprylin or grapeseed oil, respectively. The optimized lipid nanocarrier is expected to be a promising tool for promoting the skin absorption of Vit C and improving its dermatological functions.

Design of Novel Tricaprylin-Incorporated Multi-Layered Liposomal System for Skin Delivery of Ascorbic Acid with Improved Chemical Stability.

L-ascorbic acid (Vit C) possesses a variety of dermatological functions in maintaining skin health and anti-aging properties. However, its topical application is challenging owing to its liability to light, oxygen, or heat. Therefore, in this study, a novel liposomal system, including a lipophilic neutral oil named a lipo-oil-some (LOS), was designed to improve the chemical stability and aid the skin absorption of Vit C. The vesicular systems were prepared using the ethanol injection method, employing phosphatidylcholine, cholesterol, dipalmitoyl-sn-glycerol-3-phosphoglycerol, and tricaprylin as neutral oil. The optimized LOS was characterized as follows: shape, multi-layered sphere; size, 981 nm; zeta potential, -58 mV; and Vit C encapsulation efficiency, 35%. The encapsulation of the labile compound into the novel system markedly enhanced photostability, providing over 10% higher Vit C remaining compared to Vit C solution or Vit C-loaded conventional liposome under a light intensity of 20,000 lx. On the other hand, the ex vivo skin permeation and accumulation of Vit C with the LOS system were comparable to those of smaller conventional liposomes (198 nm) in a Franz diffusion cell model mounted with porcine skin. Based on these findings, we concluded that the novel liposomal system could be utilized for skin delivery of Vit C with enhanced chemical stability.

A Promising Antibacterial Wound Dressing Made of Electrospun Poly (Glycerol Sebacate) (PGS)/Gelatin with Local Delivery of Ascorbic Acid and Pantothenic Acid

A Promising Antibacterial Wound Dressing Made of Electrospun Poly (Glycerol Sebacate) (PGS)/Gelatin with Local Delivery of Ascorbic Acid and Pantothenic Acid

Improvement of ascorbic acid delivery into human skin via hyaluronic acid-coated niosomes

Hyaluronic acid (HA) as a covering agent was incorporated into the ascorbic acid (AA)-niosomes to improve the performance of AA delivery systems into the skin. The preparation method: Thin film hydration. Characterisation tests: Field emission scanning electron microscopy, fourier transform infra-red spectroscopy, dynamic light scattering, UV-Visible, zeta potential, Franz diffusion cell, and flowcytometry. The niosomes with 10% w/w HA possessed the largest mean particle diameter of 341.0 ± 48.09 nm with PDI value of 0.29 ± 0.05, and the lowest zeta potential of −38.70 ± 0.27 mv. The drug encapsulation efficiency of this sample was 56.55 ± 0.99%, and in-vitro drug release test showed AA released in two slow and fast phases. Moreover, the highest amount of drug penetration and accumulation was related to this sample, recorded 116.55 ± 7.54 and 134.8 ± 10.04 µg/cm2, respectively. Niosomes coated with 10% w/w HA showed the greatest potential for improving the antioxidant activity of AA penetration into the skin.

Locally Delivered Ascorbic Acid and β-Glycerophosphate Augment Local Bone Graft in a Murine Model of 2-Level Posterior Spinal Fusion.

Ascorbic acid is involved in collagen biosynthesis and upregulates alkaline phosphatase, potentially alleviating cell senescence and stimulating mesenchymal stem cell proliferation and differentiation into osteoblasts. We hypothesized locally delivered ascorbic acid and β-glycerophosphate act as a bone graft extender to increase the volume of new bone formed in a murine model of posterior lumbar fusion. Collagen sponges were used as delivery vehicles. Sponges were prepared with primary media alone or with the addition of ascorbic acid and β-glycerophosphate. Fresh morselized bone graft from 12 donor mice was used. Twenty-four healthy male C57BL/6 mice underwent an uninstrumented posterior L3-L5 lumbar fusion. One control group received morselized bone only. A second "sponge control" group received morselized bone with the control collagen sponge. The third group received morselized bone and a collagen sponge with ascorbic acid and β-glycerophosphate. Three months postoperatively, the lumbar spine underwent high-resolution micro-computed tomography for analysis of bone formation, density, and bridging fusion. Animals receiving ascorbic acid and β-glycerophosphate had a statistically significant increase in corrected bone volume compared with control and sponge groups, with a 56.3% and 25.4% increase, respectively. Mineralized bone fraction was statistically significantly decreased for animals in the ascorbic acid group compared with control and sponge groups. There was no significant difference in fusion rate between test groups. Locally delivered ascorbic acid and β-glycerophosphate in a murine model of posterior spinal fusion yielded statistically significant increases in new bone formation in the lumbar spine but statistically significant decreases in mineralized bone fraction. Differences in fusion rate were not statistically significant. This study provides early data suggesting that delivery of ascorbic acid to a spinal fusion site may be beneficial but does not yet establish an indication for clinical use. Further studies are needed to determine optimal dose and delivery of ascorbic acid.

Tetrahexyldecyl Ascorbate (THDC) Degrades Rapidly under Oxidative Stress but Can Be Stabilized by Acetyl Zingerone to Enhance Collagen Production and Antioxidant Effects.

Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.

Nanoemulsion-based patch for the dermal delivery of ascorbic acid

Photo-aging is caused mainly by sun radiations, which consist mainly of the ultraviolet radiation (UVA and UVB). Ascorbic acid (AA) has been widely used in the cosmetic field as an anti-wrinkle, anti-pigmentary, and antioxidant agents, however, its cosmetic application is limited due to its poor penetration across the skin, rapid oxidation, and instability of the formulation. The objective of the present study was to utilize a nanoemulsion as a nanocarrier strategy to deliver AA dermally and stabilize it. A concentration of 80 mg/mL AA was loaded into oil-in-water (O/W) nanoemulsion and characterized in terms of droplet size, zeta potential, thermodynamic stability, and morphology. Patches were then prepared using hydroxypropyl methylcellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC), AA nanoemulsion, and plasticizers (PEG 400 in Formulation 1, F1, and isopropanol in Formulation 2, F2) and evaluated in terms of stability, in vitro release, and ex vivo permeation study. The mean droplet size of the AA nanoemulsion was 14.4 ± 1.9 nm, zeta potential was close to zero. The AA nanoemulsion was physically stable showing no phase separation or turbidity after centrifugation and heating/cooling tests. The cumulative amount per area of AA permeated across Strat-M® membrane was 602.2 ± 57.9 µg/cm2. The ex vivo permeation profile showed a controlled-release profile of AA within 24 h, achieving a maximum amount of 414 µg permeated across the stratum corneum. The release fitted the Higuchi model with a correlation coefficient of 0.995. Nanoemulsion-based patches could serve a potential system for the dermal delivery of unstable hydrophilic compound

An ascorbic acid delivery system based on (W1/O/W2) double emulsions encapsulated by Ca-alginate hydrogel beads

The aim of the present study was to develop ascorbic acid (AA)-loaded (W1/O/W2) double emulsions encapsulated by Ca-alginate hydrogel beads system (AA-HB) for efficient topical delivery. Some factors related to the stability and encapsulation efficiency of AA-HB were investigated. In addition, AA-HB were evaluated for storage stability, antioxidant activity, release characteristics, and skin permeation properties. The results showed that AA-HB had good stability when stored at 4 °C and 25 °C for 60 d. Compared with AA-loaded (W1/O/W2) double emulsions (AA-DE) and AA-water solution (AA-WS), the AA-HB had a more significant sustained-release effect on AA, while the antioxidant properties of AA in AA-HB were not affected. In vitro permeation study showed that the skin permeation of AA was promoted by the synergistic effect of double emulsions and hydrogel beads. Hence, the (W1/O/W2) double emulsions encapsulated by Ca-alginate hydrogel beads might be a promising delivery system for topical applications of AA.

Electrospun wound dressing as a promising tool for the therapeutic delivery of ascorbic acid and caffeine.

Aim: The aim of this work is to formulate a wound dressing for the delivery of ascorbic acid and caffeine. Method: A wound dressing was developed from electrospun nanofiber containing ascorbic acid and caffeine. In vitro drug release was performed at 25°C and 32°C. Wound healing activity of the nanofiber mats wastested in vivo using rat model with skin excision. Antifungal activity of the dressing was tested on Candida albicans using the disc diffusion method. Results & conclusion: Zone of inhibition was 6.7mm for caffeine dressing; however, inhibition zone increased to 16.7mm for samples containing both caffeine and ascorbic acid. Animals treated with ascorbic acid showed collagen deposition and very few fibroblast cells. Blood vessels and fibroblasts were increased in caffeine-loaded dressings compared with the ascorbic acid group. The findings of the present work suggest the benefits of topical ascorbic acid and caffeine for its high wound healing effects.

INHIBITORY EFFECT OF ASCORBIC ACID MICROEMULSION ON PHOTO-OXIDIZED VIRGIN COCONUT OIL

The effect of water-in-oil (w/o) microemulsion containing ascorbic acid on photo-oxidative stability of virgin coconut oil (VCO) was investigated. To optimize the formulation, w/o microemulsions were prepared using hydrophilic lipophilic balance (HLB) concept, consisted of ternary nonionic surfactants having low, medium, and high HLB values. From this optimum HLB number, the ratio of water, surfactant and oil was determined to obtain microemulsion areas. After optimization of the microemulsion system, the storage at room temperature, and the extreme condition were conducted for testing the microemulsion stability. Then, the stable formulas were used for delivering ascorbic acid. The solubility and photo-oxidative stability of ascorbic acid microemulsion were evaluated. The optimum formula of ascorbic acid microemulsion was applied into VCO at various concentrations (0, 1, 5, and 10% w/w). Samples were subjected to photo-oxidation under fluorescent light exposure of 4000 lux for up to 8 hours. Peroxide values (PVs) and p-anisidine values (p-AnVs) of the samples were measured at 1 hour interval. The results indicated that w/o microemulsion could be formed on the HLB number of 7. W/o microemulsion containing 75% oils need surfactant concentrations of ≥ 4.5 part of water, and if containing 77.78% oils, the surfactant concentration must ≥ 5.5 part of water. These microemulsions remained stable during storage at room temperature, even after centrifugation, but did not tolerate at high temperature. The maximum solubility of ascorbic acid in w/o microemulsion was 1%. Ascorbic acid microemulsion resistant to photo-oxidation and effective inhibits that reaction in VCO. This study confirmed that w/o microemulsion can act as ascorbic acid delivery system to disperse into VCO for inhibiting its’ quality deterioration due to photo-oxidation.

INHIBITORY EFFECT OF ASCORBIC ACID MICROEMULSION ON PHOTO-OXIDIZED VIRGIN COCONUT OIL

The effect of water-in-oil (w/o) microemulsion containing ascorbic acid on photo-oxidative stability of virgin coconut oil (VCO) was investigated. To optimize the formulation, w/o microemulsions were prepared using hydrophilic lipophilic balance (HLB) concept, consisted of ternary nonionic surfactants having low, medium, and high HLB values. From this optimum HLB number, the ratio of water, surfactant and oil was determined to obtain microemulsion areas. After optimization of the microemulsion system, the storage at room temperature, and the extreme condition were conducted for testing the microemulsion stability. Then, the stable formulas were used for delivering ascorbic acid. The solubility and photo-oxidative stability of ascorbic acid microemulsion were evaluated. The optimum formula of ascorbic acid microemulsion was applied into VCO at various concentrations (0, 1, 5, and 10% w/w). Samples were subjected to photo-oxidation under fluorescent light exposure of 4000 lux for up to 8 hours. Peroxide values (PVs) and p-anisidine values (p-AnVs) of the samples were measured at 1 hour interval. The results indicated that w/o microemulsion could be formed on the HLB number of 7. W/o microemulsion containing 75% oils need surfactant concentrations of ≥ 4.5 part of water, and if containing 77.78% oils, the surfactant concentration must ≥ 5.5 part of water. These microemulsions remained stable during storage at room temperature, even after centrifugation, but did not tolerate at high temperature. The maximum solubility of ascorbic acid in w/o microemulsion was 1%. Ascorbic acid microemulsion resistant to photo-oxidation and effective inhibits that reaction in VCO. This study confirmed that w/o microemulsion can act as ascorbic acid delivery system to disperse into VCO for inhibiting its’ quality deterioration due to photo-oxidation.

Promising Chitosan-Coated Alginate-Tween 80 Nanoparticles as Rifampicin Coadministered Ascorbic Acid Delivery Carrier Against Mycobacterium tuberculosis.

The aim of this study was to design a nanocarrier system for inhalation delivery of rifampicin (RIF) in combination with ascorbic acid (ASC), namely constituted of sodium alginate coated with chitosan and Tween 80 (RIF/ASC NPs) as a platform for the treatment of pulmonary tuberculosis infection. A Box-Behnken experimental design and response surface methodology (RSM) were applied to elucidate and evaluate the effects of several factors on the nanoparticle properties. On the other hand, it was found that RIF/ASC NPs were less cytotoxic than the free RIF, showing a significantly improved activity against nine clinical strains of Mycobacterium tuberculosis (M. tb) in comparison with the free drug. RIF/ASC NPs had an average particle size of 324.0 ± 40.7nm, a polydispersity index of 0.226 ± 0.030, and a zeta potential of - 28.52 ± 0.47mV and the surface was hydrophilic. The addition of sucrose (1% w/v) to the nanosuspension resulted in the formation of a solid pellet easily redispersible after lyophilization. RIF/ASC NPs were found to be stable at different physiological pH values. In summary, findings of this work highlight the potential of the RIF/ASC NP-based formulation development herein to deliver RIF in combination with ASC through pulmonary route by exploring a non-invasive route of administration of this antibiotic, increasing the local drug concentrations in lung tissues, the primary infection site, as well as reducing the risk of systemic toxicity and hence improving the patient compliance.

Mathematical modeling of L-(+)-ascorbic acid delivery from pectin films (packaging) to agar hydrogels (food)

This paper focusses on the mathematical modeling of the ascorbic acid (antioxidant) release from a pectin edible film (packaging) to an agar hydrogel (food). The proposed model considers the viscoelastic properties of the polymeric film, the solid ascorbic acid dissolution inside the film, its degradation and diffusion in both the film and the hydrogel. By relying on the independent determination of all its parameters, the model proved to predict the ascorbic acid transport inside the agar hydrogel properly. Thus, it may be considered a powerful theoretical tool for the design of polymeric films (packaging) aimed at releasing antioxidant agents inside food.

Correction: Development of a microparticulate system containing Brazilian propolis by-product and gelatine for ascorbic acid delivery: evaluation of intestinal cell viability and radical scavenging activity.

Correction for 'Development of a microparticulate system containing Brazilian propolis by-product and gelatine for ascorbic acid delivery: evaluation of intestinal cell viability and radical scavenging activity' by Lizziane Maria Belloto de Francisco et al., Food Funct., 2018, DOI: 10.1039/c8fo00863a.

Development of a microparticulate system containing Brazilian propolis by-product and gelatine for ascorbic acid delivery: evaluation of intestinal cell viability and radical scavenging activity.

The use of propolis by-product (PBP) microparticles (MP) as delivery systems can be a promising tool to surpass drawbacks related to low stability of ascorbic acid (AA). The objective of this study was to develop and characterize MP prepared with PBP containing AA. The MP was characterized regarding morphology, particle size, polydispersity index (PDI), association efficiency (AE), drug loading (DL), infrared and Raman spectroscopy as well as antioxidant and radical scavenging activity, in vitro release, and cellular studies. MP was shown to be spherical with some agglomeration. Its particle size was 1654 ± 0.210 nm with a PDI of 0.7. The AE and DL were, respectively, 100.30 ± 2.66% and 13.16 ± 0.59. Spectroscopic studies indicated a possible interaction between the PBP and AA. 2,2-Diphenyl-1-picrylhydrazyl (DPPH˙), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays demonstrated that the MP containing AA have an excellent antioxidant capacity as well as a considerable scavenging activity against reactive oxygen and nitrogen species. The in vitro release profile showed a slow pattern of drug release of AA from MP. Viability studies with intestinal cells revealed that MP did not present toxicity in Caco-2 and HT29-MTX. Moreover, AA could permeate Caco-2 monolayers and triple co-culture substantially at the end of 8 h, opposite to the MP. Therefore, the proposed MP formulation represents a promising platform for oral delivery of AA with a local effect on intestines.

Polyamide Microparticles Containing Vitamin C by Interfacial Polymerization: An Approach by Design of Experimentation

Vitamin C is widely use in cosmetics and pharmaceutics products for its active properties. However ascorbic acid shows unfavourable chemical instability such as oxidation leading to formulation problems. Therefore, carriers, such as micro- and nanoparticles, have been widely investigated as delivery systems for vitamin C to improve its beneficial effects in skin treatment. However, none of the previous studies have been able to produce microparticles with a high encapsulation entrapment of vitamin C. The aim of the present study is to use an experimental design to optimize the synthesis of polyamide microparticles for the delivery of ascorbic acid. The effect of four formulation parameters on microparticles properties (size and morphology, encapsulation efficiency and yield, release kinetics) were investigated using a surface response design. Finally, we were able to obtain stable microparticles containing more than 65% of vitamin C. This result confirms the effectiveness of using design of experiments for the optimisation of microparticle formulation and supports the proposal of using them as candidate for the delivery of vitamin C in skin treatment.