Kamarza Mulia

Drug Release from PLGA Microspheres Attached to Solids Using Supercritical CO2

Functionalization of a porous orthopedic implant with dexamethasone, a widely used anti-inflammatory drug, encapsulated within a biodegradable polymer for controlled release could help reduce or eliminate the inflammation response by the local tissue. In this research, we investigated the possibility of using supercritical carbon dioxide (CO2) for attaching dexamethasone-loaded PLGA (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous delivery of dexamethasone. Supercritical CO2 has been shown to be effective for attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached microspheres showed similar dexamethasone release profiles but different magnitude of burst release. Microspheres attached to the porous alloy samples using supercritical CO2 at 10 bar and 40°C for 30 min showed a release profile similar to that of the nonattached microspheres. The microsphere morphology and the release profiles of microspheres attached to the glass plates and to the porous alloy samples suggest that dexamethasone burst release is enhanced by PLGA swelling at higher CO 2 pressures and better dispersion of microspheres. This study shows that microspheres can be incorporated into porous solids using supercritical CO2, allowing for a wide variety of drug-biodegradable polymer formulations prepared using the proven emulsion/solvent evaporation method to be tested.

Deacidification of palm oil using betaine monohydrate-based natural deep eutectic solvents

In the palm oil industry, the deacidification process is performed by steam stripping which causes the loss of most of palm oils natural antioxidants due to high temperature. The liquid-liquid extraction process which is carried out at low temperature is preferable in order to preserve these compounds. The use of hydrated ethanol can reduce the losses of antioxidants, but the ability of this solvent to extract free fatty acids also decreases. Betaine monohydrate-based natural deep eutectic solvents (NADES) have extensive potential for this process. The selectivity of these NADES was determined to select a preferable solvent. The betaine monohydrate-glycerol NADES in a molar ratio of 1:8 was determined to be the preferred solvent with the highest selectivity. This solvent has an efficiency of palmitic acid extraction of 34.14%, and the amount of antioxidants can be preserved in the refined palm oil up to 99%. The compounds are stable during extraction.

Isobaric heat capacity measurements for the n-pentane-acetone and the methanol-acetone mixtures at elevated temperatures and pressures

Abstract Isobaric heat capacities for the n-pentane–acetone and the methanol–acetone binary mixtures were measured with a flow calorimeter at selected temperatures from 423.1 K to 523.1 K as a function of pressure up to 10 MPa. The compositions of each mixture were 0.25, 0.50, and 0.75 mole fractions. The uncertainties of cp measurements were less than 0.4%, depending on the magnitude of the temperature differences. As part of the measurement process, liquid densities at elevated pressure and 303.1 K were also determined and reported. Experimental cp data were compared to the cp values calculated using several equations of state. In general none of the equations of state were able to reliably predict the heat capacities in the supercritical region for either mixture. For both mixtures, the use of binary interaction parameters improved the cp representation in the critical region, by effectively translating the pressures that correspond to cp maxima. However, very close to a maxima, deviations of the calculated cp were still as large as 50%, due to the deficiencies of cubic equations of state in the critical region. Comparison results are specifically presented for the Peng–Robinson equation of state

Natural deep eutectic solvents (NADES) as green solvents for carbon dioxide capture

This study was conducted to determine the effectiveness of Natural Deep Eutectic Solvent (NADES), consisting of choline chloride and a hydrogen bonding donor (HBD) compound, in terms of carbon dioxide absorption. Solubility of carbon dioxide in NADES was found to be influenced HBD compound used and choline chloride to HBD ratio, carbon dioxide pressure, and contact time. HBD and choline/HBD ratios used were 1,2-propanediol (1:2), glycerol (1:2), and malic acid (1:1). The carbon dioxide absorption measurement was conducted using an apparatus that utilizes the volumetric method. Absorption curves were obtained up to pressures of 30 bar, showing a linear relationship between the amount absorbed and the final pressure of carbon dioxide. The choline and 1,2-propanediol eutectic mixture absorbs the highest amount of carbon dioxide, approaching 0.1 mole-fraction at 3.0 MPa and 50°C. We found that NADES ability to absorb carbon dioxide correlates with its polarity as tested using Nile Red as a solvatochromic probe.

Review of angiotensin-converting enzyme inhibitory assay: Rapid method in drug discovery of herbal plants

The renin-angiotensin-aldosterone system is a signaling pathway which responsible in the blood pressure regulation. Angiotensin-converting enzyme (ACE) is one of the key elements responsible for the hypertensive mechanism. It converts angiotensin-I to angiotensin-II. The discovery history of the ACE inhibitory activity assay method has been through a long stage for decades and development continues until today. The ACE inhibitory activity has become an effective screening method in the search for new antihypertensive agents from herbal plants. Some of in vitro assay methods were used to examine the activity of ACE inhibitors based on the substrate usage, such as; Cushman and Cheung Method using a substrate hippuryl-histidyl-leucine (HHL), Holmquist method using a substrate furanacryloyl-tripeptide, Elbl and Wagner method using a substrate benzoil-[l-14C] glicyl-L-histidine-L-leucine, Carmel and Yaron method using a substrate o-aminobenzoylglycyl-p-nitrophenylalanilproline, and Lam method using 3-hydroxybutyrylglycyl-glycyl-glycine as substrate. Several different methods to measure the results of enzymatic reactions or separating substrate with products, including spectrophotometric, fluorometric, high-performance liquid chromatography, electrophoresis, and radiochemistry. Application of the test method for screening the ACE inhibitors activity and investigation of active compounds from natural products can be done easily with this method, it is very helpful in research because the results obtained are simple, accurate, and rapid.

Preparation, physical characterization, and stability of Ferrous-Chitosan microcapsules using different iron sources

Dietary modification, supplementation and food fortification are common strategies to alleviate iron deficiencies. Fortification of food is an effective long-term approach to improve iron status of populations. Fortification by adding iron directly to food will cause sensory problems and decrease its bioavailability. The purpose of iron encapsulation is: (1) to improve iron bioavailability, by preventing oxidation and contact with inhibitors and competitors; and (2) to disguise the rancid aroma and flavor of iron. A microcapsule formulation of two suitable iron compounds (iron II fumarate and iron II gluconate) using chitosan as a biodegradable polymer will be very important. Freeze dryer was also used for completing the iron microencapsulation process. The main objective of the present study was to prepare and characterize the iron-chitosan microcapsules. Physical characterization, i.e. encapsulation efficiency, iron loading capacity, and SEM, were also discussed in this paper. The stability of microenca...

Extraction of vitexin from binahong (Anredera cordifolia (Ten.) Steenis) leaves using betaine - 1,4 butanediol natural deep eutectic solvent (NADES)

The leaves of binahong (Anredera cordifolia (Ten) Steenis) contain flavonoids as bioactive substances that have efficacy to treat wounds and diseases caused by bacteria. One of the flavonoids contained in the leaves is 8-glucopyranosyl-4’5’7-trihydroxyflavone or vitexin. Conventional extraction of flavonoids from leaves of binahong has been developed and usually using non-friendly organic solvent. To overcome these problems, a Natural Deep Eutectic Solvent (NADES) is used to replace the conventional organic solvents, as it is an environmentally friendly, non-toxic and high boiling point solvent. In this study, a betaine-based NADES combined with 1,4-butanediol in 1:3 mole ratio was used as the extraction solvent. Vitexin in the extract was analyzed qualitatively and quantitatively using an HPLC. The extraction of vitexin from binahong leaves at room temperature (27 °C) for four hours give yield of 46 ppm, much lower than 200 ppm yield obtained after extraction at 55 °C for 90 minutes. This results showed ...

Effect of alginate composition on profile release and characteristics of chitosan-alginate microparticles loaded with mangosteen extract

Preparation of mangostin-loaded chitosan-alginate microparticles, chemical and physical characterization of the particles, and mangostin release profiles, are described herein. Mangostin rich fraction was obtained from Garcinia mangostana L. pericarp by extraction followed by fractionation. Mangostin-loaded chitosan-alginate microparticles were prepared by ionic gelation method using tripolyphosphate as the linking agent and various concentration of alginate. Mangostin was effectively loaded in all microparticle formulations, resulting in ∼97% encapsulation efficiencies. The loading of mangostin and the in-vitro release profiles in simulated gastrointestinal fluids were affected by the chitosan to alginate ratios used in the preparation of the microparticles. Increased alginate concentration resulted in lowered release of mangostin from microparticles immersed in simulated gastric fluid (pH 1.2) up to two hours. Low release of mangostin in acidic fluid but high release in simulated colon fluid, indicated ...

Optimization process condition for deacidification of palm oil by liquid-liquid extraction using NADES (Natural Deep Eutectic Solvent)

One of many steps in palm oil refining process is deacidification which aims to separate free fatty acids and other compounds from the oil. The deacidification process was using a green solvent, known as NADES, that consisted of betaine monohydrate and propionic acid at molar ratio of 1:8. In this study, the process conditions were optimized using the response surface method (RSM) through central composite design in order to predict the maximum distribution coefficient of palmitic acid. The obtained regression equation of the basic model for optimization was: y = 0.717 + 0.003x1 + 0.043 x2 + 0.148x3 − 0.005 x1x1 - 0.030 x2x2 + 0.047 x3x3 − 0.008 x1x2 + 0.008 x1x3 + 0.033 x2x3. The independent variables are x1 ≡ temperature (40, 60, 80 °C), x2≡ amount of palmitic acid in the palm oil (2, 5, 8 %) and x3 ≡ mass ratios of oil to NADES (1:2, 1:1, 2:1). The optimum process condition found was temperature of 62.3°C, palmitic acid content of 8%, and NADES to palm oil mass ratio of 1:2, resulting in the maximum di...

Application of Ionic Liquid as a Green Solvent for Polyphenolics Content Extraction of Peperomia pellucida (L) Kunth Herb

Background: Inhibition of phosphodiesterase 4 (PDE4) is a promising therapeutic approach for the treatment of inflammatory pulmonary disorders i.e. asthma and chronic obstructive pulmonary disease. However, the treatment with PDE4 inhibitors is not definitive due to the side effects such as nausea and vomiting which are associated with the non-selective inhibitors. Objective: To identify selective PDE4B inhibitors that are expected to be potential drug candidates for the treatment of inflammatory pulmonary disorders. Methods: A shared feature pharmacophore model for both ligand and structure-based pharmacophore models for PDE4B inhibitors was developed and used as a query in the virtual screening of Maybridge and SPECS databases. The hits were filtered based on Lipinski’s rule of five and pharmacophore fit score. Finally, the hits were docked into the active site of PDE4B and PDE4D to test their affinity and selectivity. Results: Based on the virtual screening results, nine compounds were identified as final hits, where four compounds showed the highest affinity and selectivity for PDE4B over PDE4D according to the protein-ligand interactions analysis. Conclusion: Selective PDE4B inhibitors have been identified using a combination of pharmacophore-based virtual screening and molecular docking. Those inhibitors are promising candidates for pre-clinical evaluation to justify their affinity and selectivity for PDE4B and test their anti-inflammatory activity. Key words: Asthma, Chronic obstructive pulmonary disease, Molecular docking, Phosphodiesterase 4B, Virtual screening.Objectives: To find out the effect of mild heat shock on osteoblast proliferation and mineralisation following treatment with bisphosphonates. Materials and Methods: Cell culture of MC3T3 cells was performed in alpha minimum essential medium supplemented with 10% Foetal Calf Serum (FCS), 2 mmol L-glutamine and 100U/ml each of penicillin/streptomycin and were incubated at 37°C in humidified 5% CO2. The selected bisphosphonate drugs were administered, following which heat therapy was given by placing the flasks in a temperature-regulated water bath. The proliferation of osteoblast progenitors was measured using the methylene blue staining technique. Results: The results showed that mild heat-shock for 2 min at 42°C can stimulate proliferation of osteoblast progenitors, as well as bone nodule formation. In addition, mild heat-shock can reverse the action of bisphosphonate by stimulation of osteoblast proliferation and mineralisation. Conclusion: Mild heat-shock enhances cell differentiation and osteoblasts mineralisation following bisphosphonate treatment. Key words: Bisphosphonates, Heat-shock, Osteoblast, Osteoclast.