Dewi Safitri

Multiple Functions of D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS) as Curcumin Nanoparticle Stabilizer: In Vivo Kinetic Profile and Anti-Ulcerative Colitis Analysis in Animal Model

This study was conducted to evaluate the potential benefit of particle reduction down to nanoscale on curcumin, a unique natural active compound facing therapeutic problems due to low solubility and permeability. In addition, the presence of TPGS as a surfactant for multiple functions on curcumin nanoparticle was addressed. Observation was focused on bioavailability enhancement after oral administration and local anti-inflammatory improvement after rectal dosing. Nanonization of curcumin was performed using an up-scalable top down method. Specific animal models were used to study the in vivo kinetic profile and the biological activity of curcumin nanoparticle, compared with curcumin powder. d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticle was prepared through homogenization with high pressure of the 1500 bar. An in vivo study was performed after oral administration of the preparations to male healthy Wistar rats, to monitor the plasma kinetic profile of curcumin. The biological activity study was conducted after rectal administration of the preparations in Wistar rats induced by 2,4,6-trinitrobenzene sulfonic acid to develop ulcerative colitis. The curcumin nanoparticle with a size of approximately 200 nm was successfully produced and revealed a better in vivo kinetic profile over the larger size of curcumin mixed with TPGS, with bioavailability (AUC0-∞) that was accounted for seven-fold. In addition, the TPGS-stabilized curcumin nanoparticle demonstrated a superior local anti-inflammatory effect in ulcerative colitis, indicated by the shifting of observed parameters close to the healthy status. The tremendously improved anti-inflammatory effect of the TPGS-stabilized curcumin nanoparticle was found with a very low dose. Reducing the particle size of curcumin down to ~200 nm with the presence of TPGS seems to be a promising approach to improving the therapeutic value of curcumin.

TPGS-Stabilized Curcumin Nanoparticles Exhibit Superior Effect on Carrageenan-Induced Inflammation in Wistar Rat

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

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.