Enhancement in Bioavailability of CurCousin®, A Minor Metabolite from Curcuma longa by Addition of BioPerine® —A Pharmacokinetic Study

In recent years, metabolic syndrome has been a growing health concern across the world. The role of nutraceuticals and functional foods in this area has a significant place due to the adverse effects of contemporary modes of treatment. CurCousin® is a nutritional ingredient containing bioactive Calebin A, (analog of Curcumin) with self-affirmed GRAS status. CurCousin® has been a clinically studied dietary supplement ingredient with a positive impact on body weight, lipid levels and metabolic health. Bioenhancers play an important role in increasing the bioavailability of the active in turn enhancing efficacy as well as reducing the dosage required to achieve the therapeutic effect. This study investigated the possible pharmacokinetic interaction between CurCousin® at two different doses (2.25 and 4.5 mg/kg) in the presence and absence of BioPerine® (0.27 mg/kg), a natural bioenhancer in Sprague-Dawley rats. The results revealed that the addition of BioPerine® into CurCousin® (2.25 mg/kg) half the dose when administered enhances the bioavailability and was equipotent to CurCousin® (4.5 mg/kg) double the dose without BioPerine®. Thus, leading to future clinical studies to evaluate its improved pharmacological efficacy as well as reduced therapeutic dosage.

Fabrication of taxifolin loaded zein-caseinate nanoparticles and its bioavailability in rats

Taxifolin loaded zein-caseinate nanoparticles(TZP)were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat.The formulations of TZP were optimized.With mass ratio of 1:1:2 between taxifolin,zein and sodium caseinate,the particle size andζpotential of TZP were(168.74±0.35)nm and−(57.67±0.25)mV,while the encapsulation and loading efficiency of taxifolin were(85.83±0.89)%and(17.11±0.88)%,respectively.After freeze-drying,TZP exhibited excellent redispersibility in water without aggregation.Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed.After encapsulating in TZP,the excellent dispersion of taxifolin in water signifi cantly improve its diffusion velocity through a semipermeable membrane.After oral administration,taxifolin and its 5 metabolites were identifi ed in rat plasma by ultra high performance liquid chromatography(UPLC)with quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS).The dynamic variation of taxifolin and its metabolites in plasma were then quantifi ed by UPLC with a triple-quadrupole typemass spectroscopy(UPLC-QqQ-MS/MS).A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35%to 0.52%through TZP fabrication.The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin.Glucuronidation was the dominating metabolism pathway of taxifolin in vivo.

Effect of Glycosylation on the Physicochemical Properties,Structure and Iron Bioavailability of Ferritin Extracted from Tegillarca granosa

Iron deficiency anemia(IDA)is a major global health problem.Tegillarca granosa has been considered as an excellent source of iron given its high content of iron-binding protein,ferritin.The aim of the present study was to determine the physicochemical properties,protein structures,and iron uptake of ferritin extracted from T.granosa,and to evaluate the potential impacts of chitosan glycosylation on these characteristics.Based on Box-Behnken design and response surface methodology,the optimal conditions for glycosylation included a ferritin/chitosan mass ratio of 4:1,a pH of 5.5,a reaction time of 10 min,and a reaction temperature of 50℃.Glycosylation caused decreased surface hydrophobicity and elevated water-holding capacity of ferritin due to the introduction of hydrophilic groups.Additionally,glycosylation improved antioxidant capacity of ferritin by 20.69%–189.66%,likely owing to the protons donated by saccharide moiety to terminate free radical chain reaction.The in vitro digestibility of ferritin was elevated by 22.56%–104.85%after glycosylation,which could be associated with lessβ-sheet content in secondary structure that made the glycosylated protein less resistant to enzymatic digestion.The results of the iron bioavailability in Caco-2 cells revealed that ferritin(78.85–231.77 ngmg^(−1))exhibited better iron bioavailability than FeSO4(51.48–114.37 ngmg^(−1))and the values were further elevated by glycosylation with chitosan(296.23–358.20 ngmg^(−1)),which may be related to the physicochemical properties of ferritin via glycosylation modification.These results provide a basis for the development of T.granosa derived ferritin and its glycosylated products,and can promote the utilization of aquatic resources.

A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein

Baicalein(BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide(BE-NCT) nanococrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0-t of BE-NCT nano-cocrystals(6.02-fold) was significantly higher than BE coarse powder(1-fold), BE-NCT cocrystals(2.87-fold) and BE nanocrystals(3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BENCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations.Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.

Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs

Nanocrystals,a carrier-free colloidal delivery system in nano-sized range,is an interesting approach for poorly soluble drugs.Nanocrystals provide special features including enhancement of saturation solubility,dissolution velocity and adhesiveness to surface/cell membranes.Several strategies are applied for nanocrystals production including precipitation,milling,high pressure homogenization and combination methods such as Nano-Edge^(TM),SmartCrystal and Precipitation-lyophilization-homogenization(PLH)technology.For oral administration,many publications reported useful advantages of nanocrystals to improve in vivo performances i.e.pharmacokinetics,pharmacodynamics,safety and targeted delivery which were discussed in this review.Additionally,transformation of nanocrystals to final formulations and future trends of nanocrystals were also described.

Fractions and Bioavailability of Soil Inorganic Phosphorus in the Loess Plateau of China under Different Vegetations

Plants play an important role in soil phosphorus nutrition. However, the effect of plants on phosphorus nutrition in soils of the Loess Plateau of China is not well understood. This study was conducted to reveal the relationships between plants and phosphorus＇ fractions and availability in the Loess Plateau of China. Twenty-two plant communities were surveyed and soil samples under different plant canopies were collected for the determination of soil properties and inorganic phosphorus fractionation. The results showed that Leguminosae and Lilaceae reduced pH and increased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies, while Labiatae and Rosaceae increased pH and decreased organic matter, cation exchange capacity, total and Olsen phosphorus in soils under their canopies. The contents of Ca2P, CasP, AI-P and Fe-P were highly related with soil Oisen phosphorus. They were all higher in soils under Leguminosae and Lilaceae and lower in softs under Labiatae and Rosaceae. The results of this study indicate that Leguminosae and Lilaceae improved phosphorus nutrition in soils, yet Labiatae and Rosaceae impeded the improvement of phosphorus nutrition in soils under their canopies, which will be of more help to instruct vegetation restoration in the region and provide information for soil development.

Optimal dietary copper requirements and relative bioavailability for weanling pigs fed either copper proteinate or tribasic copper chloride

Background: The objective of this study was to determine the effects of supplementing Cu on growth performance, Cu metabolism and Cu-related enzyme activities of weanling pigs fed diets with two different Cu sources, and to estimate optimal Cu requirements and relative bioavailability from these two sources for pigs.Methods: Weanling pigs were allocated to 14 treatments arranged factorially, including 6 added Cu levels(5, 10,20, 40, 80, 160 mg/kg), and 2 mineral sources(tribasic Cu chloride, TBCC and copper proteinate, Cu Pro), as well as one negative control(0 mg/kg added Cu level) and one maximum allowed level treatment(200 mg/kg TBCC) for the entire 38-d experiment. Growth performance, mineral status and enzyme activities were measured at the end of this study.Results: Increasing levels of Cu showed linear and quadratic responses(P < 0.01) for final BW, ADG and FCR regardless of the sources. Supplementation with TBCC(> 80 mg/kg) and Cu Pro(> 20 mg/kg) significantly decreased(P < 0.05) diarrhea incidence of weanling pigs. There were linear and quadratic increases(P < 0.01) in bile, hepatic,and intestinal Cu concentrations, fecal Cu contents, and plasma enzyme activities(alkaline phosphatase,ceruloplasmin, Cu, Zn-Superoxide dismutase(Cu/Zn SOD), and glutathione peroxidase), whereas plasma malondialdehyde decreased(P < 0.01) linearly and quadratically as dietary Cu level increased. Similarly, pigs fed Cu Pro absorbed and retained more Cu and excreted less Cu than those fed TBCC when supplemented 80 mg/kg and above. Optimal dietary Cu requirements for pigs from 28 to 66 d of age estimated based on fitted broken-line models(P < 0.05) of bile Cu, plasma Cu/Zn SOD and growth performance were 93–140 mg/kg from TBCC, and 63–98 mg/kg from Cu Pro accordingly. According to slope ratios from multiple linear regression, the bioavailability value of Cu Pro relative to TBCC(100%) was 156–263%(P < 0.01).Conclusion: The findings indicated that Cu recommendation from current NRC(5–6 mg/kg) was not sufficient to meet the high requirement of weanling pigs. Cu from Cu Pro was significantly more bioavailable to weanling pigs than TBCC in stimulating growth and enzyme activities, decreasing diarrhea frequency and fecal Cu contents to the environment.

Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids

The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.

Andrographolide Loaded in Micro-and Nano-Formulations: Improved Bioavailability, Target-Tissue Distribution, and Efficacy of the “King of Bitters”

Andrographolide (AG) is the characteristic constituent of Andrographis paniculata, of the Acanthaceae family. This plant is a well-known Asian medicinal plant that is widely used in India, China, and Thailand. A monograph of Herba Andrographidis (Chuanxinlian) is included in the Chinese Pharmacopoeia, which reports that this decoction can “remove heat, counteract toxicity, and reduce swellings.” The numerous potential activities of AG range from anti-inflammatory to anti-diabetic action, from neuroprotection to antitumor activity, and from hepatoprotective to anti-obesity properties. However, AG has low bioavailability and poor water solubility, which can limit its distribution and accumulation in the body after administration. In addition, AG is not stable in gastrointestinal alkaline and acidic environments, and has been reported to have a very short half-life. Among the diverse strategies that have been adopted to increase AG water solubility and permeability, the technological approach is the most useful way to develop appropriate delivery systems. This review reports on published studies related to microparticles (MPs) and nanoparticles (NPs) loaded with AG. MPs based on polylactic-glycolic acid (PLGA), alginic acid, and glucan derivatives have been developed for parenteral oral and pulmonary administration, respectively. NPs include vesicles (both liposomes and niosomes);polymeric NPs (based on polyvinyl alcohol, polymerized phenylboronic acid, PLGA, human serum albumin, poly ethylcyanoacrylate, and polymeric micelles);solid lipid NPs;microemulsions and nanoemulsions;gold NPs;nanocrystals;and nanosuspensions. Improved bioavailability, target-tissue distribution, and efficacy of AG loaded in the described drug delivery systems have been reported.

Application of hot melt extrusion to enhance the dissolution and oral bioavailability of oleanolic acid

The aim of this study was to improve the in vitro dissolution rate and oral bioavailability of oleanolic acid(OA), a water insoluble drug belonging to BCS class IV. Hot melt extrusion(HME) was applied to develop OA amorphous solid dispersions. The characterizations of the optimal formulation were performed by differential scanning calorimetry, X-ray powder diffraction, Fourier transform infrared spectroscopy and in vitro dissolution test.The in vivo pharmacokinetic study was conducted in rats. As a result, OA solid dispersion based on PVP VA 64(OA-PVP) was successfully prepared. In the dissolution medium containing 0.3% SDS, OA-PVP dramatically increased the releasing rate of OA compared with the physical mixture(PM-PVP) and commercial tablet. Furthermore, OA-PVP exhibited higher AUC(P < 0.05) and Cmax(P < 0.05) than PM-PVP and commercial tablet. The superior dissolution property and bioavailability of OA-PVP mainly attributed to the amorphous state of OA in PVP VA64 and the well dispersion caused by thermal melting and shearing. Overall, hot melt extrusion was an efficient strategy to enhance the dissolution rate and oral bioavailability of OA.

Phyto-phospholipid complexes(phytosomes): A novel strategy to improve the bioavailability of active constituents

Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly'phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes.

Improving the stability and bioavailability of tea polyphenols by encapsulations:a review

Tea polyphenols(TPPs)have attracted significant research interest due to their health benefits.However,TPPs are sensitive to certain environmental and gastrointestinal conditions and their oral bioavailability was found to be very low.Delivery systems made of food-grade materials have been reported to improve the shelf-life,bioavailability and bioefficacy of TPPs.This review discusses the chemistry of TPPs;the setbacks of TPPs for application;and the strategies to counteract application limitations by rationally designing delivery systems.An overview of different formulations used to encapsulate TPPs is provided in this study,such as emulsion-based systems(liposome,nanoemulsion,double emulsion,and Pickering emulsion)and nano/microparticles-based systems(protein-based,carbohydrate-based,and bi-polymer based).In addition,the stability,bioavailability and bioactivities of encapsulated TPPs are evaluated by various in vitro and in vivo models.The current findings provide scientific insights in encapsulation approaches for the delivery of TPPs,which can be of great value to TPPs-fortified food products.Further explorations are needed for the encapsulated TPPs in terms of their applications in the real food industry as well as their biological fate and functional pathways in vivo.

Bioavailability of bound residue derived from ^(14)C-labeled chlorsulfuron in soil and its mechanism of phytotoxicity

The bioavailability of bound residue(BR) derived from 14 C-labeled chlorsulfuron in soil and effect of the main components of the BR on growth of rape(brassica napus) and rice(Oryza sativa L.) were investigated. The results showed that the BR with the concentration of 0 28 and 0 56 nmol/g air-dried soil, which was calculated by special radioactivity of 14 C-labeled chlorsulfuron parent compound, resulted in significant depression effect on growth of rape seedling. It was assured that the main components(2-amino-4-methoxyl-6-methyl-1,3,5-triazine, 2-amino-4-hydroxyl-6-methyl-1,3,5-triazine, and 2-chloro-benzenesul-f onamide) of the BR did not inhibit the growth of rape and rice. LC-MS analysis demonstrated that the parent compound previously bound to the soil matrix could be again released and transformed into methanol-extractable residue during the course of rape growth. It was concluded that the molecular leading to the phytotoxicity to rape and rice in the BR is still the parent compound.

Bioavailability enhancers of herbal origin:An overview

Recently,the use of herbal medicines has been increased all over the world due to their therapeutic effects and fewer adverse effects as compared to the modern medicines.However,many herbal drugs and herbal extracts despite of their impressive in-vitro findings demonstrates less or negligible in-vivo activity due to their poor lipid solubility or improper molecular size,resulting in poor absorption and hence poor bioavailability.Nowadays with the advancement in the technology,novel drug delivery systems open the door towards the development of enhancing bioavailability of herbal drug delivery systems.For last one decade many novel carriers such as liposomes,microspheres,nanoparticles,transferosomes,ethosomes,lipid based systems etc.have been reported for successful modified delivery of various herbal drugs.Many herbal compounds including quercetin,genistein,naringin,sinomenine,pipeline,glycvrrhizin and nitrile glycoside have demonstrated capability to enhance the bioavailability.The objective of this review is to summarize various available novel drug delivery technologies which have been developed for delivery of drugs(herbal),and to achieve better therapeutic response.An attempt has also been made to compile a profile on bioavailability enhancers of herbal origin with the mechanism of action(wherever reported)and studies on improvement in drug bioavailability,exhibited particularly by natural compounds.

Reduction of arsenic bioavailability by amending seven inorganic materials in arsenic contaminated soil

Seven inorganic amendment materials were added into arsenic （As） contaminated soil at a rate of 0.5% （w/w）; the materials used were sepiolite, red mud, iron grit, phosphogypsum, ferrihydrite, iron phosphate, and layered double oxides （LDO）. Plant growth trials using rape （edible rape, Brassia campestris L.） as a bio-indicator are commonly used to assess As bio- availability in soils. In this study, B. campestris was grown in a contaminated soil for 50 days. All of the inorganic amend- ments significantly inhibited the uptake of As by B. campestris. Following soil treatment with the seven aforementioned inorganic ammendments, the As concentrations in the edible parts of B. campestris were reduced by 28.6, 10.5, 8.7, 31.0, 47.4, 25.3, and 28.8%, respectively, as compared with the plants grown in control soil. The most effective amendment was ferdhydrite, which reduced As concentration in B. campestris from 1.84 to 0.97 mg kg-~, compared to control. Furthermore, ferrihydrite-treated soils had a remarkable decrease in both non-specifically sorbed As and available-As by 67 and 20%, respectively, comparing to control. Phosphogypsum was the most cost-effective amendment and it showed excellent performance in reducing the water soluble As in soils by 31% and inhibiting As uptake in B. campestris by 21% comparing to control. Additionally, obvious differences in As transfer rates were observed in the various amendments. The seven amendment materials used in this study all showed potential reduction of As bioavailability and influence on plant growth and other biological processes still need to be further explored in the long term.

Bioavailability and Immunity Response in Broiler Breeders on Organically Complexed Zinc Supplementation

Two hundred and sixty four broiler breeder hens of 32 weeks of age were distributed randomly in four dietary treatments. The dietary treatments were T0: Broiler breeder ration containing 40 ppm zinc (basal 29.8 ppm + 10.2 ppm inorganic zinc), T1: T0 + organic zinc (zinc methionine) @ 20 ppm, T2: T0 + organic zinc @ 40 ppm and T3: T0 + organic zinc @ 60 ppm. The experiment was continued from 32 to 48 weeks of age. At 48 weeks, the weight of lymphoid organs, zinc levels in organs and immunity response were determined. The faecal zinc level was determined at monthly interval. The weight lymphoid organs of different treatment groups (both organic and inorganic zinc fed groups) of the broiler breeders did not differ significantly (P > 0.05). The cellular immune response of breeder birds to PHA-P was significantly (P 0.05) higher in group T3 than the rest of treated groups. The antibody titre to SRBC differed among the treated groups. The zinc content of serum of broiler breeders of all the groups did not differ significantly (P > 0.05) in all the periods of study. Zinc content in liver and tibia of broiler breeders in different dietary treatments of zinc differed significantly (P 0.05) with higher levels were obtained on increasing zinc concentration in the diet. The zinc level in the spleen and kidney of the broiler breeders in different dietary treatments did not differ significantly (P > 0.05). The average zinc content in the faeces of broiler breeder during 35 to 43 week of age did not differ significantly (P > 0.05) among the treated groups. At 48 weeks of age, zinc content of the faeces of T3 was found to be significantly (P 0.05) higher than the rest of treated groups. Similarly, during the overall experimental period analysis, it was found that zinc levels in the faeces of T2 and T3 were significantly (P 0.05) higher than T1 and T0.

Effects of Carbonate on Exchangeability and Bioavailability of Exogenous Neodymium in Soil

The effects of carbonate on the exchangeability and the bioavailability of exogenous neodymium in soil were studied by Nd-147 isotopic tracer method. Exchangeable Nd was extracted by I mol(.)L(-1) NaAc (pH8.2) in the experiment. The results indicate that whether carbonate exists in soil or not, beyond 99% of exogenous Nd is adsorbed by soil. Low-concentration carbonate (0.8 similar to 1.6 g(.)kg(-1)) can reduce exchangeable Nd concentration in soil, while high-concentration carbonate (4.0 g(.)kg(-1)) impacts little on the exchangeable Nd concentration. In addition, carbonate of 0.8 similar to 1.6 g(.)kg(-1) in soil can inhibit wheat seedlings to absorb Nd. However, when the carbonate concentration rises to 4.0 g(.)kg(-1) the inhibition will become indistinct.

Aging effect on the mobility and bioavailability of copper in soil

Aging effect on the mobility and bioavallability of copper （Cu） was investigated using a spiked soil with different incubation periods from 3 to 56 d. Wheat was planted and earthworms were cultured separately in the incubated soils. The mobility of Cu in soil was evaluated by a chemical fractionation scheme and the toxicity and bioavailability were assessed by measuring the biomass and Cu concentration in tissues. Results showed that aging had a significant effect on Cu fraction distribution, of which Cu tended to incorporate from the exchangeable into more stable fractions such as the reducible and oxidisable fractions. However, aging had little effect on Cu bioavailability to wheat and earthworm. Comparing the soil being incubated for 3 d and 56 d, Cu concentration in wheat roots decreased from 14.5 to 12.8 mg/kg, and no significant changes in Cu concentration were observed in both wheat shoots and earthworms. The Cu concentration was around 2.0 and 50 mg/kg for wheat shoots and earthworms, respectively, irrespective of soil incubation time. The CaC12-extractable Cu had a linear relationship with Cu concentration in wheat roots （R2 = 0.65, P 〈 0.05）, but no linear relationship can be found for wheat shoots and earthworms. Biological control may be more crucial for Cu accumulation in organism than the changes in soil Cu fraction caused by aging.

Assessment of Iron Bioavailability in Ten Kinds of Chinese Wheat Flours Using an in vitro Digestion/Caco-2 cell Model

Abstract Objective To compare iron bioavailability （Fe BV） from ten selected kinds of Chinese wheat flours in order to provide scientific basis for further human trials and enable plant breeding programs to screen biofortified wheat cultivars. Methods An in vitro digestion/Caco-2 cell model was used to assess Fe BV of ten flour samples from six leading Chinese wheat cultivars and the stability of Fe BV in one cultivar was studied across three growing environments. Results Significant differences were observed in both Fe BV and Fe bioavailability per gram of food （Fe BVPG） among cultivars （P〈0.01） grown at the same location with the same flour extraction rate. Zhongyou 9507 and Jingdong 8 had Fe BV 37%-54% and Fe BVP（3 103%-154% higher than the reference control. In the Anyang environment, Zhongyou 9507 had a higher wheat flour-Fe level and Fe BVPG. Differences in Fe BV were detected in cultivars with different flour extraction rates. Conclusion Zhongyou 9507 and Jingdong 8 were identified as the most promising cultivars for further evaluation of efficacy by using human subjects. The growing environments had no effect on Fe BV, but did have a significant effect on Fe BVPG. Fe bioavailabilities in low-extraction （40%） flours were higher than those in high-extraction （78%） flours.

Prodrugs incorporated into nanotechnology-based drug delivery systems for possible improvement in bioavailability of ocular drugs delivery

Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.