Annisa Rahma

Intermolecular Interactions and the Release Pattern of Electrospun Curcumin-Polyvinyl(pyrrolidone) Fiber

An electrospun fiber of polyvinyl(pyrrolidone) (PVP)-Tween 20 (T20) with curcumin as the encapsulated drug has been developed. A study of intermolecular interactions was performed using Raman spectroscopy, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The Raman and FT-IR studies showed that curcumin preferrably interacted with T20 and altered PVP chain packing, as supported by XRD and physical stability data. The hydroxyl stretching band in PVP shifted to a lower wavenumber with higher intenstity in the presence of curcumin and PVP, indicating that hydrogen bond formation is more intense in a curcumin or curcumin-T20 containing fiber. The thermal pattern of the fiber did not indicate phase separation. The conversion of curcumin into an amorphous state was confirmed by XRD analysis. An in vitro release study in phosphate buffer pH 6.8 showed that intermolecular interactions between each material influenced the drug release rate. However, low porosity was found to limit the hydrogen bond-mediated release.

Curcumin-Loaded PLA Nanoparticles: Formulation and Physical Evaluation.

Curcumin is a polyphenolic compound derived from Curcuma domestica (Zingiberaceae) that possesses diverse pharmacological effects including anti-inflammatory, antioxidant, antimicrobial, and anticarcinogenic activities. Although phase I clinical trials have shown curcumin as a safe drug even at high doses (12 g/day) in humans, poor bioavaibility largely limits its pharmacological activity. Nanoencapsulation in biodegradable polymers is a promising alternative to improve curcumin bioavaibility. In this study, curcumin was encapsulated in biodegradable polymer poly-(lactic acid) (PLA) nanoparticles via the emulsification-solvent evaporation method. Optimization of selected parameters of this method including the type of solvent, surfactant concentration, drug loading, sonication time, and centrifugation speed, were performed to obtain polymeric nano-carriers with optimum characteristics. Dichloromethane was used as the solvent and vitamin E polyethylene glycol succinate (TPGS) was used as the surfactant. Four minutes of sonication time and centrifugation at 10500 rpm were able to produce spherical nanoparticles with average size below 300 nm. The highest encapsulation efficiency was found on PLA nanoparticles containing 5% of curcumin at 89.42 ± 1.04%. The particle size, polydispersity index, zeta potential of 5% curcumin-PLA nanoparticles were 387.50 ± 58.60 nm, 0.289 ± 0.047, and −1.12 mV, respectively. Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) studies showed partial interaction between the drug and polymer.

The Influence of Formula and Process on Physical Properties and the Release Profile of PVA/BSA Nanofibers Formed by Electrospinning Technique

Electrospinning is a simple versatile process to produce nanofibers. However, it requires careful approach to form appropriates fibers for different purposes. This report describes aspects influencing successful development of nanofiber containing BSA using electrospinning method. Optical and scanning electron microscopy, energy dispersive X-Ray and Fourier transformed infrared spectroscopy, differential scanning calorimetric, and X-Ray diffraction analysis of nanofiber were performed. Modification of PVA/BSA nanofiber with Eudragit L-100 was conducted by dip coating method. The presence of BSA increased the diameter of the fibers. Modification of PVA/BSA nanofiber with Eudragit L-100 delayed the release of BSA in acidic medium but promoting its release in intestinal mimicking medium.

Correlation between Structures and Antioxidant Activities of Polyvinylpyrrolidone/Garcinia mangostana L. Extract Composite Nanofiber Mats Prepared Using Electrospinning

Nanofiber mats of polyvinyl(pyrrolidone) (PVP) with Garcinia mangostana extract (GME) as the encapsulated drug have been developed using electrospinning. SEM images of all electrospun PVP/GME composite nanofiber mats showed that they had similar and smooth morphology, no beads, and spindle shape. Its average diameter decreased and its surface area therefore increased with the decrease of its PVP concentration. The benefit of high surface area is obvious in drug delivery systems for poorly water-soluble drugs. Their FTIR spectra indicated that PVP and GME interacted intermolecularly via hydrogen bonds in the composite nanofiber mats. A conformational change in the C-H chain of PVP occurred in the composite nanofiber mats due to the intermolecular interactions. Their XRD patterns confirmed that they were amorphous because of amorphization during electrospinning. The XRD analyses also strengthened the FTIR studies; namely, GME and PVP formed intermolecular interactions in the electrospun composite nanofiber mats. As a result, GME as the encapsulated drug was molecularly dispersed in the electrospun PVP nanofiber matrix that functioned as a drug delivery system. From the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the composite nanofiber mats exhibited very high antioxidant activities despite having been exposed to high voltage during electrospinning. Therefore, they are potential antioxidant products for food and pharmaceutics.

Destabilization Mechanism of Ionic Surfactant on Curcumin Nanocrystal against Electrolytes

We have successfully developed curcumin nanosuspension intended for oral delivery. The main purpose is to improve bioavailability through enhancing its solubility. The nanoparticles were stabilized using various stabilizers, including polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (Na-CMC), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and sodium dodecyl sulfate (SDS). The average diameter of particles, microscopic appearance, and sedimentation of each preparation was observed and compared. Each stabilizer demonstrated a different degree of inhibition of particle aggregation under electrolyte-containing simulated gastrointestinal (GIT) fluid. Non-ionic stabilizers (PVA, PVP, and TPGS) were shown to preserve the nanosuspension stability against electrolytes. In contrast, strong ionic surfactants such as SDS were found to be very sensitive to electrolytes. The results can provide useful information for the formulators to choose the most suitable stabilizers by considering the nature of stabilizers and physiological characteristics of the target site of the drug.

In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of a Curcumin Nanoemulsion

Atherosclerosis and hypertension can potentially progess into dangerous cardiovascular diseases such as myocardial infarction and stroke. Statins are widely used to lower cholesterol levels while antihypertensive agents such as captopril are widely prescribed to treat high blood pressure. Curcumin, a phenolic compound isolated from Curcuma domestica, has been proven effective for a broad spectrum of diseases, including hypertension and hypercholesterolemia. Therefore, curcumin is quite promising as an alternative therapeutic compound. Our previous studies have proven a significant increase in physical properties, bioavailability, and stability of curcumin when encapsulated in a nanoemulsion. The purpose of this study was to assess the ability of the nanoemulsion in enhancing curcumin activity as a antihypertensive and antihypercholesterolemic agent. The formulation and preparation method of the curcumin nanoemulsion have been developed in our previous study. Physical characterization was performed, including measurement of droplet size, polidispersity index, zeta potential, entrapment efficiency, and loading capacity. Antihypertensive activity of curcumin was evaluated by determining Angiotensin Converting Enzyme (ACE) inhibition in vitro. A substrate for ACE, hippuryl-L-histidyl-L-leucine was allowed to react with ACE, resulting in hippuric acid formation as the product. The degree of ACE inhibition by curcumin was represented by the amount of hippuric acid formed. Antihypercholesterolemic activity of curcumin was studied using the HMG-CoA reductase assay equipped with a 96-well UV plate. This assay was based on the spectrophotometric measurement of the decrease in absorbance which represents the oxidation of NADPH by the catalytic subunit of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) in the presence of the substrate HMG-CoA. Curcumin is known to have no significant difference in inhibiting ACE compared to Captopril, but when it was incorporated in the self-nanoemulsifying carrier, it slightly increased the inhibitory effect on ACE. In contrast, the effect of curcumin in reducing cholesterol based on the HMGR assay was more pronounced. Curcumin encapsulated in a nanoemulsion showed significant cholesterol-lowering activity compared to a standard drug, pravastatin. Therefore, we conclude that curcumin does not show ACE inhibitory effects, but has potential use as an alternative therapeutic compound to treat hyperlipidaemia. Curcumin encapsulated in a nanoemulsion increased not only the HMGR inhibition, but also ACE inhibition of curcumin. These effects are suggested to be the result of improved solubility in the nanoemulsion system.

Phytosome Containing Silymarin for Oral Administration: Formulation and Physical Evaluation

Silymarin is a unique flavonoid complex isolated from milk thistle (Silybum marianum). It has been widely used as a hepatoprotective agent. Orally administered silymarin can be absorbed rapidly but only 20-50% of silymarin will be absorbed through gastrointestinal tract, resulting in low bioavailability. Those limitations are due to its low solubility, either in water and oil, and its low intestinal permeability. This study was aimed to develop silymarin-containing phytosome in order to improve the bioavailability of silymarin with sufficient safety and stability. This system consisted of silymarin-phospholipid complex prepared by solvent evaporation method, which was incorporated to form phytosome vesicles using thin layer method with various concentrations and molar ratios of silymarin and phospholipid. The vesicle size of phytosome was reduced with sonication. The results demonstrated that formula with 2% silymarin-phospholipid complex and molar ratio of silymarin to phospholipid of 1:5 showed the best phytosomal characteristics, with mean vesicle diameter of 133.534 ± 8.76 nm, polidispersity index of 0.339 ± 0.078, entrapment efficiency of 97.169 ± 2.412 %, and loading capacity of 12.18 ± 0.30 %. The preparation remained stable after freeze-thaw stability test. Analysis of Infrared spectroscopy and Differential Scanning Calorimetry confirmed the presence of physical and chemical interactions between silymarin and phospholipid within complex formation. Well formed and discrete vesicles were revealed by Transmission Electron Microscopy analysis, drug content measurement, and freeze-thaw stability test.

Mangosteen pericarp extract embedded in electrospun PVP nanofiber mats: physicochemical properties and release mechanism of α-mangostin

Background α-Mangostin is a major active compound of mangosteen (Garcinia mangostana L.) pericarp extract (MPE) that has potent antioxidant activity. Unfortunately, its poor aqueous solubility limits its therapeutic application. Purpose: This paper reports a promising approach to improve the clinical use of this substance through electrospinning technique. Methods Polyvinylpyrrolidone (PVP) was explored as a hydrophilic matrix to carry α-mangostin in MPE. Physicochemical properties of MPE:PVP nanofibers with various extract-to-polymer ratios were studied, including morphology, size, crystallinity, chemical interaction, and thermal behavior. Antioxidant activity and the release of α-mangostin, as the chemical marker of MPE, from the resulting fibers were investigated. Results It was obtained that the MPE:PVP nanofiber mats were flat, bead-free, and in a size range of 387–586 nm. Peak shifts in Fourier-transform infrared spectra of PVP in the presence of MPE suggested hydrogen bond formation between MPE and PVP. The differential scanning calorimetric study revealed a noticeable endothermic event at 119°C in MPE:PVP nanofibers, indicating vaporization of moisture residue. This confirmed hygroscopic property of PVP. The absence of crystalline peaks of MPE at 2θ of 5.99°, 11.62°, and 13.01° in the X-ray diffraction patterns of electrospun MPE:PVP nanofibers showed amorphization of MPE by PVP after being electrospun. The radical scavenging activity of MPE:PVP nanofibers exhibited lower IC50 value (55–67 µg/mL) in comparison with pure MPE (69 µg/mL). The PVP:MPE nanofibers tremendously increased the antioxidant activity of α-mangostin as well as its release rate. Applying high voltage in electrospinning process did not destroy the chemical structure of α-mangostin as indicated by retained in vitro antioxidant activity. The release rate of α-mangostin significantly increased from 35% to over 90% in 60 minutes. The release of α-mangostin from MPE:PVP nanofibers was dependent on α-mangostin concentration and particle size, as confirmed by the first-order kinetic model as well as the Hixson–Crowell kinetic model. Conclusion We successfully synthesized MPE:PVP nanofiber mats with enhanced antioxidant activity and release rate, which can potentially improve the therapeutic effects offered by MPE.

Bromelain Encapsulated in Self Assembly Nanoemulsion Exhibits Better Debridement Effect in Animal Model of Burned Skin

Bromelain is a mixture of proteolytic enzymes presence in all tissues of pineapple (Ananas comosus). It is known for clinical use as debridement for burn treatment. However, it is easily degraded by light, high temperature and pH. Nanoemulsion of bromelain is promising to increase its stability. In this study, we investigated the nanoemulsion of bromelain and its formulation into gel preparation in order to increase its efficacy for the burn treatment. Spontaneous or self-nanoemulsifying was applied to form nanoemulsion of bromelain (NEB). Bromelain was incorporated in various types of oil phase i.e virgin coconut oil (VCO), olive oil, vitamin E acetate and combination of both vitamin E acetate and VCO. Cremophor RH 40 was used together with polyethyleneglycol 400 to reduce oil-water interface tension. The stability of NEB in different oil phases was evaluated including particle size, polydispersity index, zeta potential, enzymatic activity and nanoemulsion morphology. Further, the most stable NEB was incorporated into hydrophilic gel matrix. An in vivo evaluation was carried out in hot plate-induced burn skin of New Zealand rabbit. Treatment of wounds was given by applying the preparations: NEB and the nanoemulsion bromelain-CMC gel (GKNB), using a standard protocol. As a control, untreated rabbit burned skin was provided. The efficacy of NEB was evaluated by observing wound contraction, eschar score, erythemic score, pus score and edema. After 14 days of storage, nanoemulsion using vitamin E acetate was found to be the most appropriate formula to encapsulate bromelain with good physical and chemical stabilities. This formula shows clear visual appearance with globule diameter of 74.37 nm, narrow size distribution, high loading efficiency of 97.96 %, and ability to maintain the enzymatic activity of bromelain compared to gel preparation using corresponding bromelain nanoemulsion. The vitamin E acetate nanoemulsion system shows better reduction in wound contraction until the 14th day of observation as well as other relevant parameters for wound healing effects. Taken together, bromelain formulated with the vitamin E acetate nanoemulsion improved the stability of bromelain and showed better activity to heal burnt skin on the animal model tested. The gel matrix retained the release of bromelain resulting in lower wound healing effect but it may have prolonged activity.