Sea Cucumber Sterol Alleviates the Lipid Accumulation in High-Fat-Fructose Diet Fed Mice.

The effect of marine-derived sea cucumber sterol (SS) with a special sulfate group on lipid accumulation remains unknown, although phytosterol has been proved to have many biological activities, including lowering blood cholesterol. The purpose of the present study is to investigate the alleviation of SS on lipid accumulation and the possible underlying mechanism using high-fat-fructose diet fed mice. Dietary administration with SS for 8 weeks reduced significantly the body weight gain and lipid levels in serum and liver. Especially, SS was superior to phytosterol in lowering lipid accumulation due to the great promotion of fatty acid ß-oxidation, the inhibition of cholesterol synthesis, and the acceleration of cholesterol efflux. The findings found that sea cucumber sterol exhibited a more significant effect than phytosterol on alleviating HFF-diet-induced lipid accumulation through regulating lipid and cholesterol metabolism, which might be attributed to the difference in the branch chain and sulfate group.

IN VIVO ANTI-INFLAMMATORY EFFECTS OF TARAXASTEROL AGAINST ANIMAL MODELS.

BACKGROUND: Traditional Chinese medicine Taraxacum officinale has been widely used to treat various inflammatory diseases. Taraxasterol is one of the main active components isolated from Taraxacum officinale. Recently, we have demonstrated that taraxasterol has the in vitro anti-inflammatory effects. This study aims to determine the in vivo anti-inflammatory effects of taraxasterol against animal models. MATERIALS AND METHODS: Anti-inflammatory effects were assessed in four animal models by using dimethylbenzene-induced mouse ear edema, carrageenan-induced rat paw edema, acetic acid-induced mouse vascular permeability and cotton pellet-induced rat granuloma tests. RESULTS: Our results demonstrated that taraxasterol dose-dependently attenuated dimethylbenzene-induced mouse ear edema and carrageenan-induced rat paw edema, decreased acetic acid-induced mouse vascular permeability and inhibited cotton pellet-induced rat granuloma formation. CONCLUSION: Our finding indicates that taraxasterol has obvious in vivo anti-inflammatory effects against animal models. It will provide experimental evidences for the traditional use of Taraxacum officinale and taraxasterol in inflammatory diseases.

Effect of Oxy133, an osteogenic oxysterol, on new bone formation in rat two-level posterolateral fusion model.

PURPOSE: The aim of our study was to determine the effect of Oxy133 and rhBMP2 on fusion rates and new bone formation in a rat posterolateral fusion (PLF) model. Furthermore, we examined whether Oxy133 could inhibit the adipogenesis that is often present in rhBMP2-induced fusions. METHODS: Sixty-four male Lewis rats underwent two levels PLF (L3-L5). All animals were randomly divided into eight groups based on the test compound that they received: control (DMSO), low-dose rhBMP2 (0.5 µg), high-dose rhBMP2 (5 µg), low-dose Oxy133 (5 mg), high-dose Oxy133 (20 mg), low rhBMP2 + high Oxy133, high rhBMP2 + high Oxy133, and low rhBMP2 + low Oxy133. Fusion rates were assessed 8 weeks after surgery with manual palpation and plain radiographs. Bone parameters were measured using microCT. Histology was used to evaluate adipogenesis. RESULTS: No fusion was observed in the control group. Based on the manual palpation, 100% fusion was observed in all other groups except in the low-dose rhBMP2 group (69%). At 8 weeks based on X-rays, 100% fusion was observed in the following groups: high-dose rhBMP2, low-dose Oxy133, and low rhBMP2 + low Oxy133. In the other groups, the fusion rates were between 95 and 97%, except for the low rhBMP2 group (72%). We observed similar values in BV/TV ratio at L3-4 when Oxy133 groups were compared to rhBMP2 groups alone (44.62% in high-dose Oxy133 vs. 41.47% in high-dose rhBMP2 and 47.18% in low-dose Oxy133 vs. 54.98% in low-dose rhBMP2). Trabecular thickness was slightly lower in Oxy133 groups compared to rhBMP2 when comparing low- and high-dose groups from each group (118.44 µm for high-dose Oxy133 vs. 122.39 µm for high-dose rhBMP2 and 123.51 µm for low-dose Oxy133 vs. 135.74 µm for low-dose rhBMP2). At the same time, trabecular separation was lower in Oxy133 groups compared to rhBMP2 groups. Similar trends in bone parameters were observed at the L4-5 levels. Fusion masses with low- and high-dose Oxy133 had significantly less adipocytes than rhBMP2 groups that showed robust adipocyte formation. CONCLUSION: In our study, both low-dose and high-dose Oxy133 produced solid fusions with bone densities similar or higher than in the BMP2 groups. High-dose Oxy133 group had significantly less adipocytes than high- or low-dose rhBMP2 groups. Furthermore, high-dose Oxy133 was able to significantly inhibit high-dose BMP2-induced adipogenesis when combined together. Consistent with the previous reports, our preliminary findings suggest that Oxy133 has a significant potential as an alternative to rhBMP2 in spine fusion.

Triterpene alcohols and sterols from rice bran reduce postprandial hyperglycemia in rodents and humans.

SCOPE: Hyperglycemia is a major public health problem worldwide and there is increasing demand for prevention of postprandial hyperglycemia in diabetic, prediabetic, and healthy humans. METHODS AND RESULTS: We investigated whether rice bran and triterpene alcohol and sterol preparation (TASP) lowered hyperglycemia in mice and humans. Brown rice and white rice supplemented with TASP lowered the postprandial hyperglycemia in humans. TASP and its components (cycloartenol [CA], 24-methylene cycloartanol, ß-sitosterol, and campesterol) decreased postprandial hyperglycemia in C57BL/6J mice. Glucose transport into everted rat intestinal sacs and human HuTu80 cells transfected with sodium-glucose cotransporter-1 (SGLT1) was significantly reduced by the addition of CA. Intracellular localization analysis suggested that SGLT1 translocation to the apical plasma membrane was inhibited when the cells were treated with CA. CONCLUSIONS: We demonstrated for the first time that TASP from rice bran lowered postprandial hyperglycemia in mice and humans. The smaller increase in blood glucose following TASP consumption may be due to the CA-induced decrease in glucose absorption from the intestine, which may be related to decreased membrane translocation of SGLT1.

Simultaneous determination of four furostanol glycosides in rat plasma by UPLC-MS/MS and its application to PK study after oral administration of Dioscorea nipponica extracts.

A novel, sensitive and rapid ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for simultaneous quantification of four furostanol glycosides in rat plasma was established and validated. Ginsenoside Rb1 was used as an internal standard. Plasma samples were pretreated by liquid-liquid extraction with n-butanol and chromatographed on a C18 column (2.1×50 mm i.d., 2.6 µm) using a gradient elution program consisting of acetonitrile and water (containing 0.03% formic acid and 0.1 mM lithium acetate) at a flow rate of 0.4 mL/min. Lithium adduct ions were employed to enhance the response of the analytes in electrospray positive ionization mode and multiple reaction monitoring transitions were performed for detection. All calibration curves exhibited good linearity (r>0.999) over the range of 10-20,000 ng/mL for protodioscin and 2-4000 ng/mL for protogracillin, pseudoprotodioscin and pseudoprotogracillin. The recoveries of the whole analytes were more than 80.3% and exhibited no severe matrix effect. Meanwhile, the intra- and inter-day precisions were all less than 10.7% and accuracies were within the range of -8.1-12.9%. The four saponins showed rapid excretion and relative high plasma concentrations when the validated method was applied to the PK study of Dioscorea nipponica extracts by intragastric administration at low, medium and high dose to rats. Moreover, the T(1/2) and AUC(0-t) of each compound turned out to behave in a dose-dependent pattern by comparing them at different dose levels.

Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment.

The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130 nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin-ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.

Should patients with CKD stage 5D and biochemical evidence of secondary hyperparathyroidism be prescribed calcimimetic therapy? An ERA-EDTA position statement.

This paper reflects the position of the CKD-MBD workgroup, an official working group of ERA-EDTA and of the ERBP advisory board, the official guideline-producing body of ERA-EDTA, on the topic of the use of calcimimetics in patients with CKD stage 5D, as based on two recent meta-analysis.

[Sterol extracts from Begonia Sinensis Rhizome against respiratory inflammation].

The acute and chronic respiratory tract inflammation models were made to investigate the effect and mechanism of sterol extracts from Begonia Sinensis Rhizome (BSR). The first model of acute lung injury was made with Kunming mice by inhaling cigarette smoke, then the mice were treated with different concentrations of BSR sterol extracts. Lung tissue morphology was detected by HE staining, TNF-alpha/MPO were detected by Elisa, and cPLA2 protein were, detected by Western blotting respectively. Results showed that in model group, lung sheet became real, alveolar space shrank or disappeared, alveolar septum was thickened, plenty of inflammatory cells were infiltrated, capillary blood vessels were congestive and the expression of TNF-α, MPO, cPLA2 increased; after administration, a small amount of inflammatory cells were infiltrated, alveolar septum became obvious, capillary congestion status was significantly relieved and the expression of TNF-α, MPO, cPLA2 decreased (P < 0.05). The second model of chronic respiratory tract inflammation in BALB/c mice with bronchial asthma was induced by OVA, then the mice were treated with different concentrations of BSR sterol extracts. Lung tissue morphology was detected by HE staining, indexes such as IL-4, IL-5, IL-13 were detected by Elisa, and the cPLA2 protein expression was detected by Western blotting respectively. Results showed that in model group, a lot of inflammatory cells around lung vessels and bronchi exuded, bronchial goblet cells proliferated and the expression of IL-4, IL-5, IL-13, cPLA2 increased; after administration, inflammatory and goblet cell hyperplasia reduced, the expression of IL-4, IL-5, IL-13, cPLA2 also decreased (P < 0.05). The above results showed BSR sterol extracts could resist against respiratory inflammation by inhibiting cPLA2 in a dose-dependent manner.

Hypolipidemic and antioxidant activity of enoki mushrooms (Flammulina velutipes).

According to the literatures, Flammulina velutipes contains biologically active components such as dietary fiber, polysaccharide, and mycosterol, whose effects in reducing blood sugar, blood pressure, and cholesterol have been proven. This study used the active components extracted from Flammulina velutipes powder (FVP) and Flammulina velutipes extract (FVE) to investigate the impact of these active components on lipid metabolism of hamsters. The results show that the total dietary fiber content in FVP and FVE is 29.34 mg/100 g and 15.08 mg/100 g, respectively. The total mycosterol content is 46.57 ± 0.37 mg/100 g and 9.01 ± 0.17 mg/100 g, respectively. The male hamsters were subjected to lipid metabolism monitoring by adding 1, 2, and 3% FVP or FVE into their diets for a period of 8 weeks. The animal assay results show that the 3% FVP and FVE groups have the lowest concentration of TC (total cholesterol), TG (triacylglycerol), LDL (low density lipoprotein cholesterol), and LDL/HDL (high density lipoprotein cholesterol) in the serum and liver (P < 0.05). Our results demonstrate that the addition of 3% FVP or FVE has a significant effect on the lipid metabolism in hamsters whose increased level of HDL in the serum was induced by high fat diet.

Effects of taraxasterol on iNOS and COX-2 expression in LPS-induced RAW 264.7 macrophages.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxasterol was isolated from the Chinese medicinal herb Taraxacum officinale which has been frequently used as a remedy for inflammatory diseases. Our previous study has shown that taraxasterol inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages. To elucidate the underlying mechanism responsible for these effects, in the present study, we investigated the effects of taraxasterol on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, and mitogen-activated protein kinases (MAPKs) signaling pathway in LPS-induced RAW 264.7 macrophages. MATERIALS AND METHODS: RAW 264.7 cells were pretreated with 2.5, 5 and 12.5 µg/ml of taraxasterol 1 h prior to treatment with 1 µg/ml of LPS. The mRNA expression levels of iNOS and COX-2 were examined by RT-PCR. The protein expression levels of iNOS and COX-2, and the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and c-Jun N-terminal kinase (JNK) MAPKs were measured by Western blot. RESULTS: The mRNA and protein expression levels of iNOS and COX-2 were inhibited by taraxasterol in a concentration-dependent manner. Further studies revealed that taraxasterol suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW 264.7 macrophages. CONCLUSIONS: These results indicate that taraxasterol inhibits iNOS and COX-2 expression by blocking ERK1/2 and p38 MAPKs signaling pathway.

Effect of sterol esters on lipid composition and antioxidant status of erythrocyte membrane of hypercholesterolemic rats.

Hypercholesterolemia is a major cause of coronary heart disease. Erythrocyte membrane is affected during hypercholesterolemia. The effect of EPA-DHA rich sterol ester and ALA rich sterol ester on erythrocyte membrane composition, osmotic fragility in normal and hypercholesterolemic rats and changes in antioxidant status of erythrocyte membrane were studied. Erythrocyte membrane composition, osmotic fragility of the membrane and antioxidant enzyme activities was analyzed. Osmotic fragility data suggested that the erythrocyte membrane of hypercholesterolemia was relatively more fragile than that of the normal rats' membrane which could be reversed with the addition of sterol esters in the diet. The increased plasma cholesterol in hypercholesterolemic rats could also be lowered by the sterol ester administration. There was also marked changes in the antioxidant enzyme activities of the erythrocyte membrane. Antioxidant enzyme levels decreased in the membrane of the hypercholesterolemic subjects were increased with the treatment of the sterol esters. The antioxidative activity of ALA rich sterol ester was better in comparison to EPA-DHA rich sterol ester. In conclusion, rat erythrocytes appear to be deformed and became more fragile in cholesterol rich blood. This deformity and fragility was partially reversed by sterol esters by virtue of their ability to lower the extent of hypercholesterolemia.

Enhanced oral bioavailability and tissue distribution of a new potential anticancer agent, Flammulina velutipes sterols, through liposomal encapsulation.

This study innovatively investigated the anticancer effect of Flammulina velutipes sterols (FVSs), the in vivo pharmacokinetics, and the tissue distribution of FVS-loaded liposomes. The FVS consisting of mainly 54.8% ergosterol and 27.9% 22,23-dihydroergosterol exhibited evident in vitro antiproliferative activity (liver HepG-2, IC50 = 9.3 µg mL(-1); lung A549, IC50 = 20.4 µg mL(-1)). To improve the poor solubility of FVS, F. velutipes sterol liposome (FVSL) was originally prepared. The encapsulation efficiency of ergosterol was 71.3 ± 0.1% in FVSL, and the encapsulation efficiency of 22,23-dihydroergosterol was 69.0 ± 0.02% in FVSL. In comparison to its two free sterol counterparts, the relative bioavailability of ergosterol and 22,23-dihydroergosterol in FVSL was 162.9 and 244.2%, respectively. After oral administration in Kunming mice, the results of tissue distribution demonstrated that the liposomal FVS was distributed mostly in liver and spleen. The drug was eliminated rapidly within 4 h. These findings support the fact that FVS, a potential nutraceutical and an effective drug for the treatment of liver cancer, could be encapsulated in liposomes for improved solubility and bioavailability.

Chronic hemodialysis patients without marked elevation of intact parathyroid hormone are also good candidates for early intervention with cinacalcet.

Management of calcium (Ca) and phosphorus (P) metabolism is crucial in chronic hemodialysis (HD) patients. Cinacalcet is usually used for chronic kidney disease-mineral and bone disorders (CKD-MBD) patients with elevated intact parathyroid hormone (iPTH) levels. However, a certain number of CKD-MBD patients have normal iPTH levels and are not subjected to cinacalcet therapy. Here, we evaluated the efficacy of a new treatment algorithm of early initiation of cinacalcet therapy in this subgroup of patients, mainly for correcting Ca and P metabolism. Seventy-one HD patients, including 44 patients without marked elevation of iPTH (102 < iPTH ≤ 300 pg/mL), who received cinacalcet therapy, were enrolled in this study. Serum parameters relating to CKD-MBD patient metabolism, doses of phosphate binders, and type of vitamin D sterols were compared between pre- and post-cinacalcet administration retrospectively. Sixty-four of 71 patients did not require discontinuation of cinacalcet. In these 64 patients, serum Ca (P = 0.0003), P (P = 0.0153), and iPTH (P < 0.0001) levels were significantly reduced after cinacalcet administration, even in those without marked elevation of iPTH (Ca; P < 0.0001, P; P = 0.0422, and iPTH; P = 0.0018). The proportion of patients who received vitamin D sterols was unchanged (P = 0.5930) but the proportion of patients who received maxacalcitol was significantly reduced after cinacalcet administration (P = 0.0108). The new treatment algorithm of early initiation of cinacalcet is considered to be well tolerated and effective for controlling hypercalcemia, and/or hyperphosphatemia and/or increased iPTH of CKD-MBD patients.

Cytotoxic effect of novel Flammulina velutipes sterols and its oral bioavailability via mixed micellar nanoformulation.

The aim of this study was to investigate the anti-tumor effect of sterols initially separated from Flammulina velutipes and the pharmacokinetics and tissue distribution after oral administration of F. velutipes sterol nanomicelles (FVSNs). F. velutipes sterol (FVS) consisted of mainly ergosterol (54.78%), 22,23-dihydroergosterol (27.94%) and ergost-8(14)-ene-3ß-ol (discovered for the first time in F. velutipes). In vitro cytotoxicity assay of FVS against U251 cells and HeLa cells showed that at 72h treatment, the FVS (IC50=23.42µg/mL) exhibited strong inhibitory effect against U251 cells, even overwhelmed the standard anti-tumor drug (5-fluorouracil) to an extent, while the HeLa cells were not significantly susceptible to the FVS. To improve the solubility and bioavailability of FVS, a model for insoluble anti-tumor drugs, FVSNs were prepared. In vitro characterization of FVSNs revealed satisfactory size distribution, loading capacity and encapsulation efficiency. Pharmacokinetic study in SD rats demonstrated that the mixed micellar nanoformulation significantly enhanced the bioavailability of FVS than free drug. Additionly, tissue distribution in mice manifested that the biodistribution of FVSNs as compared to the free FVS suspension were significantly improved. In conclusion, the nanomicelles developed in our study provided a promising delivery system for enhancing the oral bioavailability and selective biodistribution of FVS, a potential anti-tumor agent.

Benefit-risk assessment of plant sterols in margarine: a QALIBRA case study.

This paper presents the benefit-risk assessment of adding plant sterols to margarine as an illustration of the QALIBRA method and software. With the QALIBRA tool health effects, risks as well as benefits are expressed in a common metric (DALY) which allows quantitative balancing of benefits and risks of food intake. The QALIBRA software can handle uncertainties in a probabilistic simulation. This simple case study illustrates the data need and assumptions that go into a quantitative benefit-risk assessment. The assessment shows that the benefits of plant sterols added to margarine outweigh the risks, if any.

Enhanced oral bioavailability of a sterol-loaded microemulsion formulation of Flammulina velutipes, a potential antitumor drug.

PURPOSE: To investigate the growth inhibition activity of Flammulina velutipes sterol (FVS) against certain human cancer cell lines (gastric SGC and colon LoVo) and to evaluate the optimum microemulsion prescription, as well as the pharmacokinetics of encapsulated FVS. METHODS: Molecules present in the FVS isolate were identified by gas chromatography/mass spectrometry analysis. The cell viability of FVS was assessed with methyl thiazolyl tetrazolium (MTT) bioassay. Based on the solubility study, phase diagram and stability tests, the optimum prescription of F. velutipes sterol microemulsions (FVSMs) were determined, followed by FVSMs characterization, and its in vivo pharmacokinetic study in rats. RESULTS: The chemical composition of FVS was mainly ergosterol (54.8%) and 22,23-dihydroergosterol (27.9%). After 72 hours of treatment, both the FVS (half-maximal inhibitory concentration [IC(50)] = 11.99 µg · mL(-1)) and the standard anticancer drug, 5-fluorouracil (IC(50) = 0.88 µg · mL(-1)) exhibited strong in vitro antiproliferative activity against SGC cells, with IC(50) > 30.0 µg · mL(-1); but the FVS performed poorly against LoVo cells (IC(50) > 40.0 µg · mL(-1)). The optimal FVSMs prescription consisted of 3.0% medium chain triglycerides, 5.0% ethanol, 21.0% Cremophor EL and 71.0% water (w/w) with associated solubility of FVS being 0.680 mg · mL(-1) as compared to free FVS (0.67 µg · mL(-1)). The relative oral bioavailability (area-under-the-curve values of ergosterol and 22,23-dihydroergosterol showed a 2.56-fold and 4.50-fold increase, respectively) of FVSMs (mean diameter ~ 22.9 nm) as against free FVS were greatly enhanced. CONCLUSION: These results indicate that the FVS could be a potential candidate for the development of an anticancer drug and it is readily bioavailable via microemulsion formulations.

Dietary lipid quality affects temperature-mediated reaction norms of a freshwater key herbivore.

Temperature-mediated plasticity in life history traits strongly affects the capability of ectotherms to cope with changing environmental temperatures. We hypothesised that temperature-mediated reaction norms of ectotherms are constrained by the availability of essential dietary lipids, i.e. polyunsaturated fatty acids (PUFA) and sterols, as these lipids are involved in the homeoviscous adaptation of biological membranes to changing temperatures. A life history experiment was conducted in which the freshwater herbivore Daphnia magna was raised at four different temperatures (10, 15, 20, 25°C) with food sources differing in their PUFA and sterol composition. Somatic growth rates increased significantly with increasing temperature, but differences among food sources were obtained only at 10°C at which animals grew better on PUFA-rich diets than on PUFA-deficient diets. PUFA-rich food sources resulted in significantly higher population growth rates at 10°C than PUFA-deficient food, and the optimum temperature for offspring production was clearly shifted towards colder temperatures with an increased availability of dietary PUFA. Supplementation of PUFA-deficient food with single PUFA enabled the production of viable offspring and significantly increased population growth rates at 10°C, indicating that dietary PUFA are crucial for the acclimation to cold temperatures. In contrast, cumulative numbers of viable offspring increased significantly upon cholesterol supplementation at 25°C and the optimum temperature for offspring production was shifted towards warmer temperatures, implying that sterol requirements increase with temperature. In conclusion, essential dietary lipids significantly affect temperature-mediated reaction norms of ectotherms and thus temperature-mediated plasticity in life history traits is subject to strong food quality constraints.

Nano self-assemblies based on cholate grafted poly-L-lysine enhanced the solubility of sterol-like drugs.

The physicochemical compatibility between amphiphilic polymers and hydrophobic drugs has been recognized as an important issue for improving the drug solubilisation in polymeric micelle formulations. In this work, poly-L-lysine (PLL) grafted by cholate pendants as the only hydrophobic moiety were synthesized in order to facilitate the solubilisation of sterol drugs. Results showed that micelles formed by cholate grafted PLL encapsulated significantly higher level of prednisolone and estradiol than palmitoylated PLL micelles, whereas the solubilisation capacity of non-sterol drug (griseofulvin) is inefficient for both polymers. This suggests that higher drug-polymer incorporation can be achieved by the inclusion of hydrophobic moieties with similar architecture as the drugs, i.e. 'drug-like' functional groups, which will be useful for the future design of colloidal systems for the encapsulation of specific drug.