Sodium Ascorbyl Phosphate Research Articles

Advancing Transdermal Delivery by Zn/Ag-Electrode-Printed Iontophoretic Patch with Self-Generating Microcurrents

This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed patches increased the transdermal depth of fluorescein into the dermis, while the permeation of fluorescein was limited when Zn/C-electrode-printed patches were tested. Further permeation experiments were conducted with 3D skin models, which showed a similar trend to the above, indicating that Zn/Ag-electrode-printed patches had a higher penetration rate compared to the blank. Studies using acetyl hexapeptide-8 as a peptide drug model and sodium ascorbyl phosphate (SAP) as a hydrophilic derivative of ascorbic acid showed that the iontophoretic patch with Zn/Ag electrodes promoted more penetration of drugs than unprinted patches. The permeation of SAP exhibited a two-phase profile with a relatively rapid permeation followed by a sustained, slower permeation. The permeation of acetyl hexapeptide-8 was slower due to its higher molecular weight, but the iontophoretic patch increased the permeation up to 1.5 times more than the unprinted patch. The microcurrent generated by the patch drives the transport of small molecule components through the skin, for the controlled and efficient delivery of therapeutic agents. The flexible design, efficient microcurrent generation, and stable electrodes make the Zn/Ag-electrode-printed patch a promising tool for transdermal drug delivery.

Thermosensitive hydrogel coupled with sodium ascorbyl phosphate promotes human umbilical cord-derived mesenchymal stem cell-mediated skin wound healing in mice.

Poor survival and restricted function of transplanted stem cells are regarded as limiting their efficacy in wound recovery greatly. Consequently, it is necessary to identify innovative therapeutic strategies to solve these issues. Firstly, the biological effect of PF-127 hydrogel alone and in combination with SAP on the survival, and migration of cultured HUCMSCs was assessed by cell viability, apoptosis, and scratch wound assays. S. aureus and E. coli were used to evaluate the antibacterial activity of PF-127 plus SAP combination. Further, the ability of HUCMSCs-conditioned medium (HUCMSCs-CM) to promote the angiogenesis and migration of human umbilical vein endothelial cells (HUVECs) in vitro was evaluated using tube formation and transwell migration assays. Finally, the HUCMSCs embedded in PF-127 plus SAP scaffold were administered onto mice's excisional cutaneous wound bed. Histological and immunohistochemical analyses were employed to investigate the wound healing capacity as well as cellular responses of PF-127/HUCMSCs/SAP hydrogel. PF-127 showed cytotoxicity on HUCMSCs, whereas the addition of SAP significantly promoted cell viability and alleviated apoptosis of HUCMSCs encapsulated in PF-127 hydrogel in vitro. SAP supplementation substantially abrogated the inhibiting effect of PF-127 on the migration of HUCMSCs in vitro. The combination of PF-127 and SAP exerted an obvious bacteriostatic function on S. aureus and E. coli. Moreover, the co-treatment with SAP could remarkably enhance the stimulative effect of HUCMSCs-CM on the angiogenesis and migration of HUVECs in vitro. PF-127 combined SAP-embedded HUCMSCs transplantation resulted in a potently accelerated wound healing process, promoted the number of proliferating cells and newly formed blood vessels, as well as enhanced expression of vascular endothelial growth factor. PF-127 coupled with SAP contributes to HUCMSCs-mediated traumatic wound closure in mice by promoting cell survival, antibacterial action, and angiogenesis. Our results offered a theoretical foundation for the clinical treatment of traumatic skin defects.

FORMULATION OF SODIUM ASCORBYL PHOSPHATE (SAP) INTO O/W NANOEMULSION

Objective: Wrinkles are a natural aging consequence that are most visible on sun-exposed skin, such as the face, neck, hands, and forearms. To meet the demands of the aesthetic market, anti-wrinkle active substances have been produced. Due to its capacity to shield skin from free radicals and promote collagen activity, water-soluble vitamin c has emerged as one of the essential anti-wrinkle options. Vitamin c as an antioxidant, can reduce damage caused by free radicals. Methods: The aim of this study was to develop a water-soluble vitamin c nanoemulsion, identify the optimum formulation, and do stability tests. The method is to mix the ingredients with the same phase first, then mix the two and stabilize with surfactant. A standard procedure was used to produce the nanoemulsion, with the variation ratio of tween 80 to PEG 400 and glycerin. Then, the research went on to the evaluation involved a physical stability test utilizing centrifugation at 3375 rpm, six cycles of freeze-thaw and a thermal stability test at three distinct temperatures for four weeks. Results: The results showed that the 10% glycerin increased SAP's solubility in the oil phase. A clear and transparent nanoemulsion with fine physical and thermal stability and globule sizes less than 200 nm was produced by the optimum formula, which contained Tween 80, PEG 40, glycerin, VCO, and phosphate buffer at pH 6 in a ratio of 17:9:10:3:61. Conclusion: The formulation of Sodium Ascorbyl Phosphate has the good physical, chemical characteristic, and stability properties that makes it acceptable to use it as the primary or supplemental therapy for an anti-wrinkle agent with good efficacy and low side effects.

Trace detection of bromadiolone and brodifacoum in biological and food samples: A label-free fluorescence immunoassay based on an in situ formation strategy

The widespread use of bromadiolone and brodifacoum poses a threat to public health and initiates poisoning incidents. Conventional colorimetric enzyme-linked immunosorbent assays (ELISAs) suffer from poor sensitivity, making it difficult to meet the trace detection of analytes. In this work, we constructed a sensitive and label-free fluorescence immunoassay based on the in situ formation strategy, for the quantification of bromadiolone and brodifacoum in biological and food samples. Alkaline phosphatase, an essential enzyme in ELISA, catalyzed the substrate sodium ascorbyl phosphate to L-ascorbic acid, which reacted with ο-phenylenediamine and triggered an in situ fluorescence signal with excitation/emission wavelengths of 350/430 nm. To reduce the reaction time, Fe3+ was utilized for the in situ immunoassay system. The fluorescence signal system was introduced to conventional ELISA without any label procedures, thus resulting in higher sensitivity with a 3.8-fold improvement in the half-maximal inhibitory concentration for bromadiolone, compared with colorimetric ELISA. The calculated limits of detection for bromadiolone and brodifacoum were 0.45–0.76 and 0.34–0.58 ng/mL (ng/g) in the human serum and corn samples, respectively, with recovery values ranging from 82.0 % to 93.1 %, and a coefficient of variation lower than 13.4 %. Due to its advantages of high sensitivity, cost-effectiveness, and easy substrate fabrication, this immunoassay may offer promise for applications in poisoning diagnosis and food analysis of bromadiolone and brodifacoum.

Gelatin Microspheres Loaded with Wharton's Jelly Mesenchymal Stem Cells Promote Acute Full-Thickness Skin Wound Healing and Regeneration in Mice.

Objective: At present, there is an urgent need to develop a novel and practical therapeutic approach to accelerate the healing of acute wounds. Mesenchymal stem cell (MSC)-based therapy is emerging as a promising therapeutic approach for acute skin wounds. However, there are still challenges in clinical application of this strategy, such as low survivability, low retention time, and less engraftment in skin wounds. Approach: Wharton's jelly mesenchymal stem cells (WJMSCs) were seeded into three-dimensional (3D) gelatin microspheres (GMs) to identify the biocompatibility of GMs. WJMSCs were embedded in GMs and then encapsulated with Pluronic F-127 (PF-127) and sodium ascorbyl phosphate (SAP) combination to transplant onto acute full-thickness skin wound in mice. Histology, immunohistochemistry, and immunofluorescence assay were used to investigate the skin wound healing, dermis regeneration, collagen deposition, cell proliferation, and neovascularization. Results: Three-dimensional GM had strong biocompatibility, compared with two-dimensional adherent culturing, GM loading increased the cell viability and proliferation ability of WJMSCs. WJMSCs+GM+PF-127+SAP transplantation increased skin wound healing rate, dermis regeneration, and type III collagen deposition through improving macrophage polarization, cell proliferation, neovascularization, cell retention, and engraftment at skin wound site. Innovation: The effective 3D encapsulation technology for WJMSCs solved the main problems of cell activity and residence time during MSC transplantation. WJMSCs+GM+PF-127+SAP transplantation will be a new and effective MSC biomaterials-based therapeutic strategy for acute skin traumatic wounds. Conclusion: WJMSCs+GM+PF-127+SAP transplantation facilitated acute full-thickness skin wound healing and regeneration and might be a new and effective therapy for acute skin traumatic wounds.

Chitin Nanofibril-Nanolignin Complexes as Carriers of Functional Molecules for Skin Contact Applications.

Chitin nanofibrils (CN) and nanolignin (NL) were used to embed active molecules, such as vitamin E, sodium ascorbyl phosphate, lutein, nicotinamide and glycyrrhetinic acid (derived from licorice), in the design of antimicrobial, anti-inflammatory and antioxidant nanostructured chitin nanofibrils–nanolignin (CN-NL) complexes for skin contact products, thus forming CN-NL/M complexes, where M indicates the embedded functional molecule. Nano-silver was also embedded in CN-NL complexes or on chitin nanofibrils to exploit its well-known antimicrobial activity. A powdery product suitable for application was finally obtained by spray-drying the complexes co-formulated with poly(ethylene glycol). The structure and morphology of the complexes was studied using infrared spectroscopy and field emission scanning electron microscopy, while their thermal stability was investigated via thermo-gravimetry. The latter provided criteria for evaluating the suitability of the obtained complexes for subsequent demanding industrial processing, such as, for instance, incorporation into bio-based thermoplastic polymers through conventional melt extrusion. In vitro tests were carried out at different concentrations to assess skin compatibility. The obtained results provided a physical–chemical, morphological and cytocompatibility knowledge platform for the correct selection and further development of such nanomaterials, allowing them to be applied in different products. In particular, chitin nanofibrils and the CN-NL complex containing glycyrrhetinic acid can combine excellent thermal stability and skin compatibility to provide a nanostructured system potentially suitable for industrial applications.

Common Cosmetic Compounds Can Reduce Air Pollution-Induced Oxidative Stress and Pro-Inflammatory Response in the Skin

Introduction: Constantly increasing air pollution (AP) poses a concern affecting not only our health but also our skin. A typical manifestation of the skin damage induced by AP is its premature aging, irritation, skin barrier impairment, pigmentation disorders, and development or exacerbation of various skin diseases. For these reasons, it is crucial to protect the skin from the negative effects of AP. In this study, we evaluated the ability of some compounds commonly used in dermatological or cosmetic preparations with various biological activities to reduce AP-induced skin damage. Methods: We established a new experimental model using porcine skin explants exposed to cigarette smoke (CS) in which we determined the level of reactive oxygen species (ROS) in the stratum corneum, skin barrier lipids peroxidation, and gene expression of the pro-inflammatory cytokine interleukin 6 in the epidermis. Then, we tested several polysaccharides and their derivatives such as sodium hyaluronate (SH) of different molecular weight (MW, 1.6 MDa, 300 kDa, 15 kDa, 5 kDa), yeast glucomannan, schizophyllan, and carboxymethyl β-glucan, then vitamin C derivative sodium ascorbyl phosphate, niacinamide, and D-panthenol for their ability to prevent CS-induced skin damage. For the evaluation and comparison of their mechanism of action, film-forming effect was determined by TEWL and gloss measurements and the antioxidant properties were assessed by DPPH assay. Results: In the skin samples exposed to CS, we observed significant negative changes such as the presence of large amount of ROS in the stratum corneum, high level of skin barrier lipids peroxidation and upregulated IL6 gene expression. Pretreatment of the skin samples with all the tested substances significantly prevented CS-induced skin damage. The most effective were high MW SH probably due to its best film-forming effect and sodium ascorbyl phosphate with the best antioxidant properties. Conclusion: AP leads to a significant skin damage which can be effectively prevented using some conventional cosmetic and dermatological ingredients with various mechanisms of action.

Wharton\u2019s jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat

BackgroundDiabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton’s jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored.MethodsFirstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay.ResultsIn diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo.ConclusionPF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.

Use of antioxidants to restore bond strength after tooth bleaching with peroxides.

This review compiles the literature on the antioxidants used after tooth bleaching with either low or high-concentrated carbamide and hydrogen peroxide to recover the bond strength. Antioxidants used in bleached teeth are mainly natural and non-enzymatic, except for catalase. Commonly, antioxidants are applied to remove any reactive oxygen species (ROS) residues left from bleaching gels, which adversely affect adhesive procedures, such as restorations or orthodontic brackets bonding. Even though sodium ascorbate, the most thoroughly investigated antioxidant, showed the most efficient bond strength recovery at 10% concentration, its performance depends on the type of solution and the application time. Natural extracts, such as proanthocyanidins and green tea, showed satisfactory results in the reversal of bond strength at 5% and 10% concentrations, respectively. Sodium ascorbyl phosphate, α-tocopherol, and catalase exhibited promising results, but further research is required. The adhesive system type plays an important role in the outcome of enamel bond strength after the antioxidant application. The postponement of either restorations or orthodontic brackets cementation following bleaching procedures seems to be efficiently replaced by antioxidant application prior to bonding procedures. However, the efficacy of using an antioxidant to recover bond strength depends on its type and application time.

Effect of sodium ascorbyl phosphate on osteoblast viability and differentiation.

Sodium ascorbyl phosphate (SAP) is a hydrophilic and stable L-ascorbic acid derivative, being converted by the cell phosphatases into free ascorbic acid (AA), which allows its sustained release in the medium. AA participates in the maintenance and healing of the periodontium. It presents a regulatory role of the osteoblastic activity, stimulating the deposition of collagen extracellular matrix followed by the induction of genes associated with the osteoblastic phenotype. It also acts in the elimination of reactive oxygen species, abundantly produced by defense cells in periodontal disease. The aim of this study was to evaluate the effect of SAP on osteoblast viability and differentiation. Mouse preosteoblastic cells of the MC3T3-E1 strain were used. Cell viability was assessed by the trypan blue dye exclusion assay and the expression of genes related to osteoblast differentiation by quantitative PCR. Collagen I secretion was evaluated by ELISA, and mineralized matrix formation was assayed by Alizarin red S staining. The results showed that SAP at concentrations from 50 to 500µmol/L does not influence preosteoblast cell viability, but stimulates their differentiation, observed by the induction of RUNX2, COL1A1, and BGLAP2; by the higher secreted levels of collagen I; and also by the increase in the mineralization of the extracellular matrix in cells exposed to this agent at 200 or 400µmol/L, compared with those not exposed. By its stability and capacity to induce preosteoblastic cell differentiation, our results indicate that the incorporation of SAP into local release devices, membranes/scaffolds or biomaterials, could favor bone tissue formation and therefore periodontal healing.

PF-127 hydrogel plus sodium ascorbyl phosphate improves Wharton\u2019s jelly mesenchymal stem cell-mediated skin wound healing in mice

BackgroundFactors such as poor engraftment, retention, and survival of the transplanted stem cells are deemed to limit their therapeutic efficacy for wound regeneration. Hence, it is necessary to explore these issues in order to resolve them. In this study, we aim to investigate the role of Pluronic F-127 (PF-127) hydrogel plus antioxidant sodium ascorbyl phosphate (SAP) in enhancing Wharton’s jelly mesenchymal stem cell (WJMSC)-mediated effectiveness on full-thickness skin wound healing in mice.MethodsFirst, the cytotoxicity of PF-127 and the biological effect of SAP on the survival of WJMSCs were tested in vitro using cell viability and proliferation assays. Next, a cell suspension containing WJMSCs, PF-127, and SAP was topically administered onto an 8-mm diameter excisional full-thickness wound bed. Eight days after transplantation, the mice were sacrificed and the skin tissue was excised for histological and immunohistochemical analysis. Finally, in vivo distribution of transplanted WJMSCs was traced to investigate cell engraftment and the potential therapeutic mechanism.ResultsPF-127 was found to be cytotoxic to WJMSCs while SAP significantly improved the survival of PF-127-embedded WJMSCs. When this combination was topically transplanted onto the wound bed, wound healing was facilitated and dermis regeneration was achieved on the 8th day after surgery, as evidenced by an increase in dermal thickness, newly developed hair follicles, and collagen fiber deposition accompanied by a reduction in scar width. Further, immunohistochemical analysis demonstrated a higher number of anti-inflammatory M2 macrophages, proliferating cells, and newly formed blood vessels in the WJMSCs/PF-127/SAP group relative to all other groups. In addition, in vivo tracking results revealed a highly enhanced engraftment of WJMSCs accumulated in the dermis in the WJMSCs/PF-127/SAP group.ConclusionsSAP significantly improves the survival of WJMSCs in PF-127 encapsulation. Further, PF-127 plus SAP is an effective combination that enhances WJMSC engraftment in the dermis, which then promotes full-thickness wound healing through potential M2 macrophage formation and angiogenesis.

DEVELOPMENT OF MICROEMULSION AND WATER/OIL/WATER MULTIPLE EMULSION CONTAINING BETA-ARBUTIN, LACTIC ACID, AND SODIUM ASCORBYL PHOSPHATE

Objective: In addition to lactic acid and sodium ascorbyl phosphate, which have whitening effects, beta-arbutin is a safe whitening agent for skin.Combining these three substances should reduce the concentration of each one in a formula and achieve an optimal whitening effect. In this study,microemulsions and water/oil/water (W/O/W) multiple emulsions were applied to produce a formula containing these whitening agents.Methods: All the active ingredients were formulated into microemulsions and W/O/W multiple emulsions with different concentrations of Tween 80and Span 80 as emulsifiers to obtain a stable formula. Twelve-week physical stability studies were performed for every formula at low (4±2°C), room(28±2°C), and high (40±2°C) temperatures.Results: The produced microemulsions were transparent with a mean droplet size of 15.50 nm. In addition, the W/O/W multiple emulsions containeddroplets within droplets, which were dispersed in a continuous phase with an inner droplet size of 0.15 μm and an outer droplet size of 0.37 μm. TheW/O/W multiple emulsions showed pseudoplastic thixotropic flow properties. Furthermore, the microemulsions were stable at low (4±2°C) androom (28±2°C) temperatures, while the W/O/W multiple emulsions were stable at room (28±2°C) and high (40±2°C) temperatures.Conclusion: It was concluded that the combination of beta-arbutin, lactic acid, and sodium ascorbyl phosphate was suitable for formulating intomicroemulsions as well as W/O/W multiple emulsions as whitening cosmetic products.

Stability of sodium ascorbyl phosphate in the water-glycerol system

Sodium ascorbyl phosphate is a hydrophilic derivative of ascorbic acid with better stability compared to the parent compound. However, sodium ascorbyl phosphate is not as stable in solution as it is in the solid state, and it has been found to degrade, with accompanying discoloration, under the influence of different conditions. Here, the degradation mechanism of sodium ascorbyl phosphate in the water-glycerol system was revealed and the thermal degradation kinetics was shown to follow second-order kinetics. A thermal degradation prediction model was established and successfully fitted to the experimental data. In addition, the stability of sodium ascorbyl phosphate in the water-glycerol system during storage was investigated under different conditions, including changes in concentration, temperature, pH, light and oxygen, and metal ions. Sodium ascorbyl phosphate content was quantitatively measured via HPLC, and the color and pH values of the sample were qualitatively measured using a spectrophotometer and a pH meter, respectively. It was found that temperature and pH are the most important factors affecting the stability of sodium ascorbyl phosphate.

Development and Evaluation of Sodium ascorbyl phosphate Nanoemulsion for Transcutaneous Delivery

Sodium ascorbyl phosphate (SAP) nanoemulsion has been developed using several methods with the aim of improving its skin permeation by transcutaneous delivery. SAP is a hydrophilic derivate of ascorbic acid with low permeability. Development of the formulation began with the utilization of glycerin as the solvent as well as co-surfactants, combined with the addition of amphiphilic molecules and lipophilic surfactants. Amphiphilic molecules and lipophilic surfactants formed complexes and emulsion, respectively, then underwent colyophilization prior to incorporating the lyophilizate to form nanoemulsion. Polyethylene glycol (PEG) 20000 and lecithin were used as the amphiphilic molecules, while Span 80 was employed as lipophilic surfactants. These methods aimed to improve the permeability of SAP, thus enhancing its permeation across the stratum corneum. The highest SAP solubility was achieved by adding 10% glycerin, which meant the glycerin could be used to increase the lipophilicity of SAP in the formulation. The amount of SAP partitioned into the oil phase was mixed by solid-in-oil dispersion (SOD) with PEG 20000, lecithin, and Span 80 was determined indirectly by measuring the concentration of SAP in the aqueous phase. The globule sizes of the SAP-PEG 20000 and SAPlecithin nanoemulsions were 50–200nm and > 500nm for the SAP-Span 80 nanoemulsion. The amount of diffused SAP was varied in an in vitro permeation study using the Franz diffusion cell, snake skin (Python R.) and Spangler's as a membrane models. This study indicates that SAP could penetrate in to the skin by SOD method and its potential utility to improve the skin permeation of hydrophilic molecules.

Effect of sodium ascorbyl phosphate on promotion of osteoblast differentiation and its application to treatment of periodontal disease

Effect of sodium ascorbyl phosphate on promotion of osteoblast differentiation and its application to treatment of periodontal disease

Co-Spray-Dried Urea Cross-Linked Hyaluronic Acid and Sodium Ascorbyl Phosphate as Novel Inhalable Dry Powder Formulation

The pathogenesis and progression of several lung disorders is propagated by inflammatory and oxidative processes, which can be controlled by adjunctive inhaled therapies. The present study aimed to develop an inhalable dry powder formulation consisting of co-spray-dried urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate (SD HA-CL–SAP), a novel combination which was recently shown to possess anti-inflammatory, antioxidant, and wound healing properties. Native HA and SAP were co-spray dried (SD HA–SAP) and evaluated as control formulation. Yield (Y%) and encapsulation efficiency (EE%) were 67.0 ± 4.8% and 75.5 ± 7.2% for SD HA–SAP, 70.0 ± 1.5% and 66.5 ± 5.7% for SD HA-CL–SAP, respectively. Both formulations were shown to be suitable for lung delivery in terms of morphology, particle size (median volumetric diameter ∼ 3.4 μm), physical and thermal stability, in vitro aerosol performance - respirable fraction: 30.5 ± 0.7% for SD HA–SAP and 35.3 ± 0.3% for SD HA-CL–SAP. SAP release was investigated using Franz cells and air-interface Calu-3 cell model (>90% of SAP transported within 4 h). The innovative SD HA-CL–SAP formulation holds potential as inhalable dry powder for the treatment of inflammatory lung disorders.

In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) – LYO HA-CL – SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL – SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL – SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ± 27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL – SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Influence of Emollient on the Preparation and stability of Sodiun Ascorbyl Phospate Cream

As a type of cosmetic preparation products, cream dosage form is widely used with the addition of active substances having antioxidant activities, such as vitamin C and its derivatives. Sodium ascorbyl phosphate (SAP) can be used in topical formulation due to its more stable properties than ascorbic acid. However, it is difficult to deliver SAP into the dermis in a suficient dose. To overcome the problem, occasionally we can add a penetration enhancer. In some literature, emollients that often added in cosmetic preparations also have another effect as a penetration enhancer. The purpose of this research was to observe wether emollient addition could influence the penetration of SAP in the cream formulation or not. SAP was formulated into four formulations with three different emollients: dimethicone (F1), capric triglyceride (F2), and isopropyl myristate (F3) and a formulation without the addition of emollients (F4). The diffusion test was performed by Franz's diffusion cell method using male wistar rat’s abdominal membrane as a standard model of the skin barrier. The result of stability test showed that SAP cream was stable at room temperature but unstable on freeze thaw condition described by significant different values for all formulas. Nonetheless, the diffusion test showed that F2 with the capric triglyceride as emollient had the highest ability to pass SAP through the membrane, followed by isopropyl miristate. We concluded that emollient addition could influence the penetration of the cream of SAP.Keywords: vitamin c, ascorbic acid, sodium ascorbyl phospate, emollient, penetration enhancer

Formulation and Characterization of Native and Crosslinked Hyaluronic Acid Microspheres for Dermal Delivery of Sodium Ascorbyl Phosphate: A Comparative Study.

The present work evaluates for the first time the use of urea-crosslinked hyaluronic acid (HA-CL), a novel derivative of native hyaluronic acid (HA), to produce microspheres (MS) by emulsification-solvent evaporation, for dermal delivery of sodium ascorbyl phosphate (SAP). As the term of comparison, HA MS were prepared. A pre-formulation study—investigation of the effects of polymers solutions properties (pH, viscosity) and working conditions—led to the production of optimized HA-CL MS and HA-CL—SAP MS with: almost unimodal size distributions; mean diameter of 13.0 ± 0.7 and 9.9 ± 0.8 µm, respectively; spherical shape and rough surface; high yield, similar to HA MS and HA–SAP MS (≈ 85%). SAP was more efficiently encapsulated into HA-CL MS (78.8 ± 2.6%) compared to HA MS (69.7 ± 4.6%). Physical state, thermal properties, relative moisture stability of HA-CL MS and HA-CL–SAP MS were comparable to those of HA MS and HA–SAP MS. However, HA-CL–SAP MS exhibited an extended drug release compared to HA–SAP MS, despite the same kinetic mechanism—contemporaneous drug diffusion and polymer swelling/dissolution. Therefore, HA-CL formulation showed a greater potential as microcarrier (for encapsulation efficiency and release kinetic), that could be improved, in future, using suitable excipients.

Combination of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate for the treatment of inflammatory lung diseases: An in vitro study

This in vitro study evaluated, for the first time, the safety and the biological activity of a novel urea-crosslinked hyaluronic acid component and sodium ascorbyl phosphate (HA-CL – SAP), singularly and/or in combination, intended for the treatment of inflammatory lung diseases. The aim was to understand if the combination HA-CL – SAP had an enhanced activity with respect to the combination native hyaluronic acid (HA) – SAP and the single SAP, HA and HA-CL components. Sample solutions displayed pH, osmolality and viscosity values suitable for lung delivery and showed to be not toxic on epithelial Calu-3 cells at the concentrations used in this study. The HA-CL – SAP displayed the most significant reduction in interleukin-6 (IL-6) and reactive oxygen species (ROS) levels, due to the combined action of HA-CL and SAP. Moreover, this combination showed improved cellular healing (wound closure) with respect to HA – SAP, SAP and HA, although at a lower rate than HA-CL alone. These preliminary results showed that the combination HA-CL - SAP could be suitable to reduce inflammation and oxidative stress in lung disorders like acute respiratory distress syndrome, asthma, emphysema and chronic obstructive pulmonary disease, where inflammation is prominent.