DISEASE PREVENTION FUNCTIONAL FOODS FROM THE HIGH POTENTIAL MMP-2 INHIBITION ACTIVITY OF PINEAPPLE JUICE GRANULE

Objective: This study aimed to compare total phenolic acid and protein contents as well as free radical scavenging, enzyme activities of fresh and fermented pineapple juice. Methods: The dried pineapple juice, prepared by freeze-drying and granulation method, with high bioactive compounds (total phenolic acid and protein contents) and biological activities (scavenging and enzyme activities) from fresh and fermented pineapple juice was developed and evaluated. The selected granules were evaluated for their stability at the 3 different temperatures for 3 mo. The pineapple juice granules were tested for the non-cytotoxic concentration by the SRB assay and Matrix metalloproteinase 2 (MMP-2) inhibition activity on human skin fibroblast. Results: The pineapple juice granules, the single-coated granules of pineapple juice showed a higher percentage of yield but lower biological contents and activities than that triple-coated granules. The triple-coated granules of pineapple juice exhibited the highest total protein content (1.53±0.10 mg Bovine serum albumin equivalent (BSAE)) with scavenging activity (51.15±5.94 %), and enzyme activity (4156.18±74.78 Casein digestion unit (CDU)/mg). For gelatinolytic activity on MMP-2, the freeze-dried powder and triple-coated granules of pineapple juice indicated the highest MMP-2 inhibition activity of 50.74% and 48.48%, respectively. Conclusion: The triple-coated granules of pineapple juice could be served as a disease prevention functional food due to its easy operation, high total phenolic acid, and protein contents with high potential MMP-2 inhibition activity

‘Tablet-in-syringe’: A novel dosing device for dysphagic patients containing fast disintegrating tablets fabricated using semi-solid extrusion 3D printing

With the ability to fabricate personalized dosage forms and considerably shorter manufacturing time, semisolid extrusion (SSE) 3D printing has rapidly grown in popularity in recent years as a novel, versatile manufacturing method that powers a wide range of applications in the pharmaceutical field. In this work, the feasibility of using SSE 3D printing to fabricate fast-disintegrating tablets (FDTs) that are pre-filled in dosing syringes was evaluated. The novel design approach, ‘tablet-in-syringe’, was aimed to ease the oral drug administration and improve the dosing accuracy for dysphagic patients. The effect of varying polymer (hydroxypropyl methylcellulose E15) concentrations and printing parameters (e.g., extrusion rate) on dimensional accuracy, physicochemical properties, disintegration time, and content uniformity of 3D-printed FDTs was studied. An overall comparison of results demonstrated that the best FDT formulation among those developed was with a polymer:drug ratio (w/w) of 1:30, printed at extrusion rate of 3.5 μL/s. The diameter of printed filaments of this formulation was observed to be similar to the nozzle diameter (22G), proving that good printing accuracy was achieved. This FDTs also had the fastest disintegration time (0.81 ± 0.14 min) and a drug (phenytoin sodium, as the model drug) content uniformity that met pharmacopeial specifications. Although the flow characteristics of the dissolved formulation still need improvement, our findings suggested that the novel ‘tablet-in-syringe’ could potentially be considered as a promising fast-disintegrating drug delivery system that can be personalized and manufactured at—or close to—the point of care for dysphagic patients using SSE

Characterization of hydrophilic polymers as a syringe extrusion 3D printing material for orodispersible film

The application of hydrophilic polymers in designing and three-dimensional (3D) printing of pharmaceutical products in various dosage forms has recently been paid much attention. Use of hydrophilic polymers and syringe extrusion 3D printing technology in the fabrication of orodispersible films (ODFs) might hold great potential in rapid drug delivery, personalized medicine, and manufacturing time savings. In this study, the feasibility of 3D-printed ODFs fabrication through a syringe extrusion 3D printing technique and using five different hydrophilic polymers (e.g., hydroxypropyl methylcellulose E15, hydroxypropyl methylcellulose E50, high methoxyl pectin, sodium carboxymethylcellulose, and hydroxyethylcellulose) as film-forming polymers and printing materials has been investigated. Rheology properties and printability of printing gels and physicochemical and mechanical properties of 3D-printed ODFs were evaluated. Amongst the investigated hydrophilic polymers, sodium carboxymethylcellulose at a concentration of 5% w/v (SCMC-5) showed promising results with a good printing resolution and accurate dimensions of the 3D-printed ODFs. In addition, SCMC-5 3D-printed ODFs exhibited the fastest disintegration time within 3 s due to high wettability, roughness and porosity on the surface. However, the results of the mechanical properties study showed that SCMC-5 3D printed ODFs were rigid and brittle, thus requiring special packaging to prevent them from any damage before practical use

Wound healing effect of supercritical carbon dioxide Datura metel l. leaves extracts : an in vitro study of anti-inflammation, cell migration, MMP-2 inhibition, and the modulation of the sonic hedgehog pathway in human fibroblasts

Datura metel L. (thorn apple) has been used in Thai folk wisdom for wound care. In this study, we chose supercritical carbon dioxide extraction (scCO2) to develop crude extraction from the leaves of the thorn apple. The phytochemical profiles were observed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). The biological activities of D. metel were performed through antioxidant assays, anti-inflammation based on the Griess reaction, the migration assay, the expression of matrix metalloproteinase-2 (MMP-2), and regulatory genes in fibroblasts. Dm1 and Dm2 extracts were obtained from scCO2 procedures at different pressures of 300 and 500 bar, respectively. Bioactive compounds, including farnesyl acetone, schisanhenol B, and loliolide, were identified in both extracts. The antioxidant properties of both D. metel extracts were comparable to those of l-ascorbic acid in hydrogen peroxide-induced fibroblasts with no significant difference. Additionally, Dm1 and Dm2 significantly inhibited the nitrite production levels of 1.23 ± 0.19 and 1.52 ± 0.05 μM, respectively, against the lipopolysaccharide-treated group (3.82 ± 0.39 μM). Interestingly, Dm1 obviously demonstrated the percentage of wound closure with 58.46 ± 7.61 and 82.62 ± 6.66% after 36 and 48 h of treatment, which were comparable to the commercial deproteinized dialysate from the calf blood extract. Moreover, both extracts were comparable to l-ascorbic acid treatment in their ability to suppress the expression of MMP-2: an enzyme that breaks down collagen. The gene expressions of SHH, SMO, and GLI1 that control the sonic hedgehog pathway were also clearly upregulated by Dm1. Consequently, the scCO2 technique could be applied in D. metel extraction and contribute to potentially effective wound closure

CARBOPOL®-GUAR GUM GEL AS A VEHICLE FOR TOPICAL GEL FORMULATION OF PECTIN BEADS LOADED WITH RUTIN

Objective: The aim of this study was to develop suitable pharmaceutical gel formulations of pectin beads using semisynthetic celluloses or synthetic carbomers as a gelling agent.Methods: Low methoxyl pectin (LMP) beads loaded with rutin composing 3% Non-amidated LMP, 15% sorbitol and 1% NaHCO3 with 2% w/v of rutin were prepared, characterized, incorporated in various pharmaceutical gel bases and evaluated for rabbit skin irritation by close patch test.Results: Rutin wetted bead formulation which showed spherical shape (around 700 µm), high rutin encapsulation efficiencies (82.02±0.91%), low conductivity (900 µS at 30 min) and faster rutin release (more than 80% in 30 min) was selected to incorporate in gel. The wetted rutin beads exhibited good stability (beads suspended in gel without breaking or gel color changing) in the gel composed of 0.4% w/v Carbopol® Ultrez 21 with 0.04% w/v guar gum at pH 5.0.  Conclusion: Rutin wetted beads in developed pharmaceutical gel formulation showed higher percentages of rutin remaining when stored at room temperature (27±2ºC) than non-loaded rutin of about 1.53 times and gave no irritation in rabbit skin irritation test, however, the safety on human skin applications should be confirmed. Keywords: Carbopol®, guar gum, pharmaceutical gel, pectin, rutin, bead

STABILITY ENHANCEMENT OF CELASTRUS PANICULATUS SEED OIL BY LOADING IN NIOSOMES

Objective: To investigated the bioactive compounds, biological activities and also developed the stability enhancement system for bioactive compounds in Celastrus paniculatus seed oil (CPSO)Method: This study has investigated the bioactive compounds including fatty acid profile and total phenolic contents, antioxidative and tyrosinase inhibition activities of CPSO. Then, various blank niosomes formulations were prepared. The stability of CPSO was enhanced by loading CPSO in niosomes, CPSO loaded niosomes were determined their physical properties such as size, zeta potential and chemical stability of oleic acid.Results: CPSO gave not only high contents of fatty acids especially cis-9- oleic acid (43.99 % w/w) but also the total phenolic compounds, γ-tocopherol and α-tocopherol that played an important role for the tyrosinase inhibition. CPSO exhibited superior tyrosinase inhibition activity than the standard ascorbic acid, kojic acid and arbutin. The maximum loading of the CPSO in selected niosomes (1:1 molar ratio of Tween61:cholesterol) was 2.00 % w/v with the average particle size of loaded niosomes about 230 nm and zeta potential of -46 mV. In the stability studied, the CPSO loaded niosomes showed higher oleic acid content than CPSO solution indicating the substance protection after loading in niosomes after 3 months storage.Conclusion:  Niosomes loaded with CPSO appeared to be a suitable method for the enhancement stability of the CPSO bioactive compounds because of not only the low toxicity, biodegradable, biocompatible, non-immunogenic but also skin penetration enhancer of niosomes as well. Keywords: Celastrus paniculatus seed oil (CPSO), niosomes, stability enhancement, tyrosinase inhibition activity Â

Formulation and Characterization of Nicotine Microemulsion-Loaded Fast-Dissolving Films for Smoking Cessation

The present study aimed to develop a nicotine microemulsion (NCT-ME) and incorporate it into a fast-dissolving film. The NCT-ME was prepared by mixing the specified proportions of nicotine (NCT), surfactant, co-solvent, and water. The NCT-ME was measured by its average droplet size, size distribution, zeta potential, and morphology. NCT-ME fast-dissolving films were prepared by the solvent casting technique. The films were characterized by morphology, weight, thickness, disintegration time, and mechanical strength properties and the determined NCT loading efficiency and in vitro drug release. The results showed that almost all NCT-MEs presented droplet sizes of less than 100 nm with a spherical form, narrow size distribution, and zeta potentials of −10.6 to −73.7 mV. There was no difference in weight and thickness between all NCT-ME films, but significant changes in the disintegration times were noticed in NCT40-Smix[PEG-40H(2:1)]10 film. The mechanical properties of films varied with changes in type of surfactant. About 80% of the drug release was observed to be between 3 and 30 min. The drug release kinetics were fitted with the Higuchi matrix model. The NCT40-Smix[P-80(1:1)]10 film showed the highest dissolution rate. It was concluded that the developed ME-loaded fast-dissolving film can increase drug release to a greater extent than the films without ME

SELECTIVE ANTICANCER ACTIVITY OF CURCUMA XANTHORRHIZA FERMENTED JUICES

Objective: The objective of this study was to investigate the anticancer activity and toxicity of fermented juices from six Thai plants, Garcinia mangostana Linn., Tinospora crispa Linn., Litchi chinensis Sonn., Dimocarpus longan Lour., Curcuma xanthorrhiza (CX) Roxb., and Averrhoa bilimbi Linn., in normal cells as compared with common commercial fermented juices.Methods: The plants were fermented for 3 months, and their biological activities including 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging, metal chelating, lipid peroxidation inhibition, and tyrosinase inhibition activities were subsequently evaluated. Furthermore, their in vitro anticancer activities in human colon adenocarcinoma (HT-29), cervical cancer (HeLa), hepatocellular carcinoma (HepG2), and murine melanoma (B16F10) cell lines and their toxicities in normal human skin fibroblasts were assessed.Results: The fermented juice of CX showed a higher antioxidant activity than those of the other plants, with an SC50 (DPPH scavenging) value of 0.011 mg/mL, an IPC50 (lipid peroxidation inhibition) of 0.027 mg/mL, an MC50 (metal chelating) value of 0.170 mg/mL, and an IC50 (tyrosinase inhibition) of 0.027 mg/mL. Moreover, the fermented juice of CX displayed selective toxicity in cancer cell lines (HeLa, HepG2, and B16F10), with a significantly lower toxicity in normal human skin fibroblasts as compared with an expensive commercial fermented juice product.Conclusion: The present study suggests that the fermented juice of CX can be developed as a functional food supplement with antioxidant properties or as an anticancer product with low toxicity to normal human skin fibroblasts

Fabrication and Characterization of Low Methoxyl Pectin/Gelatin/Carboxymethyl Cellulose Absorbent Hydrogel Film for Wound Dressing Applications

In this study, hydrogel films composed of low methoxyl pectin (LMP), gelatin, and carboxymethyl cellulose (CMC) were fabricated. Glycerin was used as a plasticizer while glutaraldehyde (Glu) and calcium chloride (CaCl2) were used as crosslinking agents in film preparation. Hydrogel films were morphologically characterized and evaluated for mechanical properties. In addition, the investigations for fluid uptake ability, water retention capacity, water vapor transmission rate, and integrity value of the invented films were performed. The results showed that F-Glu-Ca-G30 film demonstrated superior properties when compared to other prepared films. It demonstrated a high percentage of elongation at break (32.80%), fluid uptake ability (88.45% at 2 h), water retention capacity (81.70% at 2 h), water vapor transmission rate (1889 g/m2/day), and integrity value (86.42%). F-Glu-Ca-G30 film was subsequently selected for 10% w/w povidone iodine (PI) loading and tested for anti-Staphylococcus aureus activity using an agar diffusion assay. Notably, F-Glu-Ca-G30-PI film demonstrated a dramatic ability to inhibit microbial growth, when compared to both a blank film and iodine solution control. Our LMP/gelatin/CMC hydrogel film promises to be an effective dressing material with high fluid absorption capacity, fluid holding ability, and water vapor transmission rate. Incorporation of antibiotics such as povidone iodine into the films conferred its antimicrobial property thereby highlighting its potential dermatological use. However, further clinical studies of the application of this hydrogel film as wound dressing material is recommended

Use of Orange Oil Loaded Pectin Films as Antibacterial Material for Food Packaging

This study aims to develop orange oil loaded in thin mango peel pectin films and evaluate their antibacterial activity against Staphylococcus aureus. The mango peel pectin was obtained from the extraction of ripe Nam Dokmai mango peel by the microwave-assisted method. The thin films were formulated using commercial low methoxy pectin (P) and mango pectin (M) at a ratio of 1:2 with and without glycerol as a plasticizer. Orange oil was loaded into the films at 3% w/w. The orange oil film containing P and M at ratio of 1:2 with 40% w/w of glycerol (P1M2GO) showed the highest percent elongation (12.93 ± 0.89%) and the lowest Young’s modulus values (35.24 ± 3.43 MPa). For limonene loading content, it was found that the amount of limonene after the film drying step was directly related to the final physical structure of the film. Among the various tested films, P1M2GO film had the lowest limonene loading content (59.25 ± 2.09%), which may be because of the presence of numerous micropores in the P1M2GO film’s matrix. The inhibitory effect against the growth of S. aureus was compared in normalized value of clear zone diameter using the normalization value of limonene content in each film. The P1M2GO film showed the highest inhibitory effect against S. aureus with the normalized clear zone of 11.75 mm but no statistically significant difference. This study indicated that the orange oil loaded in mango peel pectin film can be a valuable candidate as antibacterial material for food packaging