Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies.

Lipid-based drug delivery systems (LbDDS), such as self-nanoemulsifying drug delivery systems (SNEDDS), constitute a prominent formulation approach for enhancing the aqueous solubility and oral bioavailability of poorly water-soluble compounds. Utilization of biorefinery wastes, such as oil from rice bran, may prove advantageous to both improving drug solubilization and absorption and to achieving sustainable agri-food waste valorization. Here, we assessed the effect of four SNEDDS compositions differing in the oil (rice bran oil and corn oil) and surfactant type (Kolliphor RH40 and EL) on the oral bioavailability of fenofibrate, a BCS class II compound. Prior to the in vivo oral administration of the SNEDDS in rats, drug solubilization was tested in vitro using the static digestion model, followed by the ex vivo permeability study of the predigested SNEDDS using the non-everted gut sac model. No significant variation was observed in the solubilization capacity within the different SNEDDS formulations. On the other hand, the ex vivo permeability data of the predigested SNEDDS correlated well with the in vivo bioavailability data designating the superiority of rice bran oil with Kolliphor EL as the surfactant, to enhance the oral absorption of fenofibrate. Results indicated that valorization of agro-industrial waste such as rice bran oil may prove useful in enhancing the oral performance of LbDDS in the case of fenofibrate, while at the same time maximizing the use of agricultural by-products via the creation of new sustainable value chains in the pharmaceutical field.

Duration of stunting impacts compensatory growth and carcass quality of farmed milkfish, Chanos chanos (Forsskal, 1775) under field conditions.

An 18-months field trial was performed to explore the effect of duration of stunting on growth, digestive enzymes and carcass quality in Chanos chanos. Milkfish fry (weight of 1.25 ± 0.03 g and length of 5.53 ± 0.03 cm) were stocked in earthen ponds of 0.02 ha, in triplicate, for different duration of stunting, viz., 4 months (Treatment-1; T4), 8 months (Treatment-2; T8) and 12 months (Treatment-3; T12) and a normal seed (Control; C) separately. In the stunting phase, fish were stocked at higher stocking density (0.2 million/ha) and fed de-oiled rice bran at sub-optimal level. Post-stunting or re-feeding phase commenced immediately after completion of respective stunting duration and fish were reared for the rest of the period to complete the total rearing period of 18 months. In post-stunting, fish stocking density was adjusted to (5000 pieces/ha) and fed at an optimum level (3%). At the end of stunting phase, the study found a significant reduction in growth, survival, digestive enzymes activity, except protease in the T4 group, and carcass nutrients composition of stunted fish. However, in the initial phase of post-stunting, T8 group exhibited an elevated specific growth rate (5.00 ± 0.092%/day), body weight gain (80.82 ± 1.28 g), amylase (0.585 ± 0.021 U/mg protein), protease (5.48 ± 0.13 U/mg protein), and lipase activity (7.92 ± 0.32 U/mg protein). All stunted fish groups displayed a compensatory growth response in post-stunting, but a complete growth compensation was observed in T8 group, which resulted in better feed conversion ratio (3.03 ± 0.04) feed efficiency ratio (0.33 ± 0.01), protein efficiency ratio (1.91 ± 0.03), survival (91.38 ± 0.07%) and digestive enzyme activities. Similarly, at the end of post-stunting, carcass analysis revealed a complete restoration of nutrients in stunted fish and significantly higher protein content in T8 group. Further, the study found lower meat and higher bone contents in normally reared fish than the post-stunted fish which revealed the carcass quality improvement in post-stunted fish thus indicates superiority of the stunting process over normal rearing. Overall, the study suggests that stunting of milkfish, for 8 months (T8), positively affects its growth, survival, digestive enzyme activities and carcass quality which in turn, shall help to overcome the contemporary challenges in milkfish culture.

Development and Characterization of a Self-Nanoemulsifying Drug Delivery System Comprised of Rice Bran Oil for Poorly Soluble Drugs.

Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets' behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100 nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4 h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.

Effect of rice bran oil addition on the oxidative degradation and fatty acid composition of soybean oil during heating.

BACKGROUND: Rice bran oil (RBO) contains significant amounts of micronutrients (oryzanol, tocotrienol, tocopherol, phytosterols etc.) that impart a high resistance to thermal oxidation of the oil. The high oxidative stability of RBO can make it a preferred oil to improve the oxidative and flavor stabilities of other oils rich in PUFAs. In this study, the changes in the oxidative status and fatty acid composition in soybean oil (SO) blended with RBO under extreme thermal conditions were evaluated. METHODS: The blends were prepared in a volume ratio of 10:90, 20:80, 40:60, and 60:40 (RBO:SO). The changes in the oxidative parameters and fatty acid composition of the samples during heating at frying temperature (170°C) were determined using analytical and instrumental methods. Oxidative alteration was also monitored by recording FTIR spectra of oil samples. RESULTS: The increase in oxidative parameters (free fatty acid, color, specific extinctions, peroxide value, p-anisidine value, and thiobarbituric acid value) was greater in pure SO as compared to RBO or blend oils during heating. This indicates that the SO samples incorporated with RBO have the least degradation, while pure SO has the highest. Blending resulted in a lower level of polyunsaturated fatty acids (PUFA)  with       a higher level of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA). During heating, the relative content of PUFA decreased and that of SFA increased. However, the presence of RBO in SO slowed down the oxidative deterioration of PUFA. In FTIR, the peak intensities in SO were markedly changed in comparison with blend oils during heating. The reduction in the formation of oxidative products in SO during thermal treatment increased as the concentration of the RBO in SO increased; however, the levels of the protective effect of RBO did not increase steadily with an increase in its concentration. CONCLUSIONS: During thermal treatment, the generation of hydroperoxides, their degradation and formation of secondary oxidative products as evaluated by oxidative indices, fatty acids and IR absorbances were lower in blend oils compared to pure SO. In conclusion, RBO can significantly retard the process of lipid peroxidation in SO during heating at frying temperature.

Rice Bran Oil Improves Insulin Resistance by Affecting the Expression of Antioxidants and Lipid-Regulatory Genes.

The present study investigated the molecular effects of rice bran oil (RBO) on lipid-regulatory genes (sterol regulatory element binding protein-1 [Srebf1] and peroxisome proliferator-activated receptors-α [Ppara]) and the expression of catalase (CAT) and superoxide dismutase (SOD1) genes in insulin-resistant rats. Rats were divided into five groups: animals that received standard diet (control); rats fed standard diet containing RBO as the sole source of fat (RBO); a high-fructose diet (HFD) group, which was further divided into two subgroups: rats fed HFD either for only 1 month (HFD1) or for 2 months (HFD2) and rats fed HFD containing RBO for 1 month; while rats in the last group fed HFD for 30 days then treated with RBO for another 30 days. The HFD induced a state of insulin resistance (IR) as indicated by the hyperinsulinemia and elevated homeostasis model assessment insulin resistance index. Hepatic lipid levels and radical scavenging enzymes were altered by the HFD. Lipid-regulatory genes, Srebf1 and Ppara, were upregulated while Sod1 and Cat were downregulated in insulin-resistant rats. Addition of RBO to the two diet regimens alleviated the disorders of IR to some extent. RBO reduced the hepatic levels of triacylglycerol, malondialdehyde, SREBP, and PPAR-α mRNA. Hepatic SOD and CAT were elevated at gene and protein levels. The HFD induces de novo lipogenesis by upregulating the lipid-regulatory genes resulting in increased serum and hepatic triacylglycerol. Moreover, IR induced by the HFD caused a state of oxidative stress. Supplementation of RBO to fructose-fed rats not only improves insulin resistance but also downregulates lipogenic genes and improves the unbalanced oxidative status.

Development of Colorectal-Targeted Dietary Supplement Tablets Containing Natural Purple Rice Bran Oil as a Colorectal Chemopreventive.

Colorectal cancer occurs due to various factors. The important risks are dietary lifestyle and inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis. It has been found that the inhibitory enzyme cyclooxygenase-2 (COX-2) in the colorectal region can potentially reduce the risk of colorectal cancer. The present study investigated rice bran oil from natural purple rice bran, which exhibits antioxidant and anti-inflammatory activity. This study aimed to evaluate the bioactive compound content of natural purple rice bran oil (NPRBO) derived from native Thai purple rice and the anti-inflammatory activity of NPRBO in colorectal cancer cells, and to develop a colorectal delivery platform in the form of film-coated tablets. NPRBO from the rice bran of five different Thai purple rice cultivars, namely Khao’ Gam Leum-Phua (KGLP), Khao’ Gam Boung (KGB), Khao’ Gam Thor (KGT), Khao’ Gam Pah E-Kaw (KGPEK), and Khao’ Niaw Dam (KND), were extracted using the supercritical carbon dioxide extraction technique. The amount of γ-oryzanol (ORY), tocotrienols, and tocopherols present in NPRBOs and the in vitro anti-inflammatory activity of NPRBO were investigated. The highest anti-inflammatory NPRBO was transformed into a dry and free-flowing powder by liquisolid techniques. Then, it was compressed into core tablets and coated with Eudragit®L100 and Eudragit® NE30D. The in vitro release study of the film-coated NPRBO tablets was performed in three-phase simulated gastrointestinal media. The cultivar KGLP was superior to the other samples in terms of the ORY, tocotrienol and tocopherol contents and anti-inflammatory activity. Aerosil® was the most suitable absorbent for transforming NPRBO into a free-flowing powder and was used to prepare the NPRBO core tablets. The in vitro KGLP-NPRBO film-coated tablet release profile showed that no ORY was released at gastric pH while 85% of ORY was released at pH 7.4 after 6 h; this would be expected to occur in the colorectal area. Therefore, this study demonstrates the potential of KGLP-NPRBO to prevent colorectal cancer via a specific colorectal dietary supplement delivery system.

Comparative evaluation of fermented and non-fermented de-oiled rice bran with or without exogenous enzymes supplementation in the diet of Labeo rohita (Hamilton, 1822).

A 60-day feeding trial was conducted to study the effect of exogenous enzymes (xylanase and phytase) supplementation in the non-fermented and fermented de-oiled rice bran (DORB)-based diet of Labeo rohita. Four test diets (T1-DORB-based diet, T2-fermented DORB-based diet, T3-phytase and xylanase supplemented DORB-based diet, and T4-phytase and xylanase supplemented fermented DORB-based diet) were formulated and fed to the respective groups. Test diets T3 and T4 were supplemented with 0.01% xylanase (16,000 U kg-1) and 0.01% phytase (500 U kg-1) enzymes. One hundred twenty juveniles of L. rohita, with an average weight 5.01 ± 0.02 g, were stocked in 12 uniform size plastic rectangular tanks in triplicate with 10 fishes per tank following a completely randomized design (CRD). Exogenous enzyme supplementation to the T3 group significantly improved the growth performance of L. rohita (p < 0.05). Fermented DORB fed groups registered significantly lower growth irrespective of the supplementation of exogenous enzymes. The carcass composition (except CP %), enzyme activities (except amylase activity), globulin, and A/G ratio did not vary significantly (p > 0.05). Based on the results of the present study, it is concluded that exogenous enzyme supplementation significantly increases the growth of fish fed with DORB-based diet.

Presence of orally administered rice bran oil γ-oryzanol in its intact form in mouse plasma.

Although the beneficial effects (e.g., lipid-lowering activity) of γ-oryzanol (OZ), a mixture of ferulic acid esters of plant sterols and triterpene alcohols, have been extensively investigated, few studies have evaluated the absorption and metabolism of OZ. Moreover, it is unclear whether OZ, once ingested, is directly absorbed by the intestine into the bloodstream at a sufficient level to exhibit activity. Here, we prepared OZ concentrate from purified rice bran oil (Rice Oil OZ), determined the concentration of OZ in the preparation (cycloartenyl ferulate equivalent concentration; 52.2%), and then carried out chromatography-mass spectrometry analysis of plasma samples from mice after oral administration of Rice Oil OZ. The OZ concentrations of plasma from the control (vehicle-treated) mice were low (trace levels); however, at 5 h after a single oral administration of the Rice Oil OZ (600 mg per kg body weight), the levels significantly increased, reaching 17.6 ng mL-1 for cycloartenyl ferulate, 28.2 ng mL-1 for 24-methylenecycloartanyl ferulate isomers, 15.6 ng mL-1 for campesteryl ferulate, and 5.1 ng mL-1 for ß-sitosteryl ferulate, respectively, expressed in equivalence of cycloartenyl ferulate in plasma. These results provided the first mass spectrometric evidence suggesting that a portion of orally administered OZ is directly absorbed by the intestine and is present in the intact form in plasma. The presence of a significant amount of OZ in its intact form in plasma may explain the beneficial effects of OZ in vivo.