Bioavailability Enhancement Research Articles

Quality by design (QbD)-based fabrication of atazanavir-loaded nanostructuredlipid carriers for lymph targeting: bioavailability enhancement using chylomicron flow block model and toxicity studies.

Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs). Lipid concentrations, surfactant concentrations, and pressure of high-pressure homogenizer were identified as CMAs and CPP. ATV-NLCs were prepared by emulsification-high pressure homogenization method and further lyophilized to obtain solid-state NLCs. The effect of formulation variables (CMAs and CPP) on responses like particle size (Y1), polydispersity index (Y2), and zeta potential (Y3) was observed by central composite rotatable design (CCRD). The data were statistically evaluated by ANOVA for confirmation of a significant level (p < 0.05). The optimal conditions of NLCs were obtained by generating design space and desirability value. The lyophilized ATV-NLCs were characterized by DSC, powder X-ray diffraction, and FT-IR analysis. The morphology of NLCs was revealed by TEM and FESEM. In vitro study suggested a sustained release pattern of drug (92.37 ± 1.03%) with a mechanism of Korsmeyer-Peppas model (r2 = 0.925, and n = 0.63). In vivo evaluation in Wistar rats showed significantly higher (p < 0.001) plasma drug concentration of ATV-NLCs as compared to ATV-suspension using chylomicron flow block model. The relative bioavailability of ATV-NLCs was obtained to be 2.54 folds. Thus, a safe and promising drug targeting system was successfully developed to improve bioavailability and avoiding first-pass effect ensures to circumvent the acute-toxicity of liver.

Appraising the Competency of Lipid Nano-Platforms as Non-invasive Paradigms for the Treatment of Ocular Inflammations: A review

Ocular inflammation is one of the common ophthalmic disorders triggered by different underlying causes and affecting both anterior and posterior segments of the eye. The functional barriers within the eye greatly impede the efficient ocular drug delivery, and hence the efficient relief of inflammation. The conventional treatment approaches are often limited to the topical applications of eye solutions, suspensions or ointments, in addition to the intravitreal injections in case of diffuse inflammatory conditions. These strategies suffer from poor patient acceptance and compliance because of their ineffectiveness and lack of safety. During the past few decades, a research attention was focused on the development of innovative ophthalmic dosage forms. Lipid nano-platforms had particular importance in drug delivery in terms of safety, biocompatibility, sustainment of drug release, enhancement of drug bioavailability, and hence patient compliance. This review attempts to highlight the current state of lipid-based nanocarriers as a promising non-invasive approach in the management of superficial and diffuse ocular inflammations with special emphasis on their reported outcomes, and also to focus on future perspectives to fill the gaps in this area.

Nicotianamine-Chelated Iron Positively Affects Iron Status, Intestinal Morphology and Microbial Populations In Vivo (Gallus Gallus)

Abstract Objectives Iron (Fe) fortification involves low dose delivery of bioavailable Fe fortificants to food products during manufacture (or point-of-use) and is an effective population-based strategy to combat human Fe deficiencies that affect over 2 billion people globally. Iron fortification of wheat flour is now mandatory in 75 countries worldwide, however, the tendency of Fe fortificants to oxidize and cause undesired organoleptic and sensory properties pose significant challenges. Nicotianamine (NA) is a natural chelator of Fe and zinc (Zn) in higher plants and NA-chelated Fe is highly bioavailable in vitro. In graminaceous plants NA serves as the biosynthetic precursor to 2′ -deoxymugineic acid (DMA), a related Fe chelator and enhancer of Fe bioavailability, and increased NA/DMA biosynthesis has proved an effective Fe biofortification strategy in several cereal crops. In this study we aimed to investigate the impact of NA-chelated Fe on Fe status and gastrointestinal health in vivo. Methods We utilized the versatile chicken (Gallus gallus) model to assess NA-chelated Fe when delivered to chickens through intraamniotic administration (short-term exposure) or over a period of six weeks as part of a biofortified wheat diet containing increased NA, Fe, Zn and DMA (long-term exposure). Results Following short-term exposure, chickens that received an NA-chelated Fe treatment demonstrated significantly increased blood serum Fe, intestinal goblet cell number, and abundance of Bifidobacterium relative to chickens that received control Fe treatments (either EDTA-chelated Fe or unchelated Fe). Following long-term exposure, chickens that consumed the biofortified diet had significantly increased liver Fe, liver and muscle glycogen, and intestinal goblet cell number, as well as significantly different microbial population diversities (including a greater abundance of Bifidobacterium and Lactobacillus) relative to chickens that consumed the control diet. Conclusions Taken together these results demonstrate numerous health benefits associated with NA-chelated Fe in a biofortified wheat diet and uncover novel impacts of NA-chelated Fe on gastrointestinal health and functionality. Funding Sources This work was supported by grants from the USDA-ARS and HarvestPlus.

Loading of apigenin extracted from parsley leaves on colloidal core-shell nanocomposite for bioavailability enhancement

Apigenin, as a bioactive compound, exhibits a wide range of health beneficial properties; however, its therapeutic application is limited because of its poor water-solubility and low bioavailability. In the present study, apigenin was isolated and purified from parsley leaves and to enhance its bioavailability, it was loaded on the zein-lecithin nanocomposite, which was fabricated by the antisolvent coprecipitation method. The developed nanocomposite was characterized by DLS, zeta-potential, FTIR, XRD, FE-SEM, and TEM analyses. Under optimum apigenin formulation condition (pH 4, zein:lecithin mass ratio of 1:5 and apigenin dosage of 1.5 mg) the mean particle size, PDI and zeta-potential of the nanocomposite were 132.4 nm, 0.16 and −31.9 mV, while the apigenin loading and encapsulation efficiency were 4.7% and 77.4%, respectively. The developed spherical zein-lecithin nanocomposite had higher apigenin encapsulation efficiency compared to the single nanoparticles of zein and lecithin, and the stability of apigenin significantly improved against sunlight irradiation. Results showed that the synthesized nanocomposite was pH-sensitive where 87% of the encapsulated apigenin could be released from the nanocomposite under acidic pH. Loading of apigenin into the zein-lecithin nanocomposite promoted the cytotoxic effects of apigenin against Saos2 cell lines up to 75.77% in vitro, while no significant side effect on normal fibroblast cells was observed. • Apigenin (Ap) was obtained by purifying ultrasonic extract of parsley leaves. • We developed Ap/zein-lecithin nanocomposite by antisolvent coprecipitation. • Loading of AP on nanocomposite enhanced its photostability. • Ap/Z-L was pH-sensitive and considerable amount of Ap released under acidic pH. • Significant cytotoxicity against Saos2 cell lines was demonstrated.

Gamma sterilization and in vivo evaluation of cationic nanostructured lipid carriers as potential ocular delivery systems for antiglaucoma drugs

Solid lipid nanoparticles and nanostructured lipid carriers showed promising results for enhancement of ocular bioavailability of drugs with poor corneal permeability. One of these drugs is methazolamide, which is an orally administered carbonic anhydrase inhibitor for glaucoma treatment. However, sterilization by autoclaving may result in loss of the physical properties of lipid nanoparticles such as particle size and surface charge. Here, we evaluated gamma radiation as an alternative sterilization method. Methazolamide loaded nanostructured lipid carriers were optimized using 23 factorial design. Optimized formulations contained 6% lipid (85% solid lipid (Cetostearyl alcohol and glyceryl behenate) and 15% oil either medium chain triglycerides or isopropyl myristate) stabilized by 2% polysorbate 80 and 0.15% stearylamine. Nanoparticles were cationic, smaller than 500 nm, and had an entrapment efficiency of about 30%. They released methazolamide within 8 hours and showed a 5-fold enhanced reduction in intraocular pressure compared to methazolamide solution. Gamma sterilization was superior to autoclaving in preserving entrapped methazolamide, size, and surface charge of lipid nanoparticles. These findings demonstrate that gamma radiation is a viable alternative to autoclaving for sterilizing lipid nanoparticles. Moreover, this proves that nanostructured lipid carriers enhance pharmacological response of topically administered methazolamide for treating glaucoma.

Perspectives of Bacillus coagulans MTCC 5856 in the production of fermented dairy products

Probiotic bacteria protect against gastroenteritis, promote toxin reduction, cholesterol reduction, improved digestion and good function, mineral bioavailability enhancement. Bacterial strains, including Lactobacillus and Bifidobacterium, are generally used in probiotic food production. However, they are weakly resistant to the stomach's aggressive environment and high temperature, which can result in significant loss of viable probiotic microorganisms. Application of spore-forming bacteria Bacillus coagulans MTCC 5856 allows developing an innovative natural dairy fermented product with high probiotic microorganism viability (p < 0.05) during the technological process, storage period, at different pH values, and in the presence of bile salts when examining in vitro. Due to the low caseolytic activity of Bacillus coagulans, the proper ratio and fermentation temperature with the use of auxiliary starter culture Streptococcus thermophilus were established. The addition of milk protein improves the rheological characteristics of the product. Bacillus coagulans and Streptococcus thermophilus maintained more than 8 Log10 CFU/g of viable microorganisms during the product storage within 60 days. The use of Bacillus coagulans allows increasing the fermented product's antioxidant activity versus the antioxidant activity of the product when Streptococcus thermophilus is used alone. The results showed that the fermented dairy product itself to be an excellent carrier of Bacillus coagulans.

Investigating the Potential of Transdermal Delivery of Avanafil Using Vitamin E-TPGS Based Mixed Micelles Loaded Films.

To avoid the first-pass metabolism of avanafil (AVA) and its altered absorption in the presence of food after oral administration, this study aimed to investigate the potential of TPGS-based mixed micelle (MM)-loaded film for transdermal delivery and the enhancement of bioavailability. A Box–Behnken design was employed to optimize the permeation behavior of AVA from the transdermal film across the skin. The variables were the hydrophile-lipophile balance (HLB) of the surfactant (X1), the concentration of mixed micelles (MMs) in the film (X2), and the concentration of the permeation enhancer (X3). The initial permeation of AVA after 1 h (Y1), and the cumulative permeation of AVA after 24 h (Y2) were the dependent variables. Ex vivo studies were carried out on freshly isolated rat skin to investigate the drug’s permeation potential and results were visualized using a fluorescence laser microscope. Moreover, the pharmacokinetic behavior after a single application on male Wistar rats, in comparison with films loaded with raw AVA, was evaluated. The results showed that the optimum factor levels were 9.4% for the HLB of the surfactant used, and 5.12% MMs and 2.99% penetration enhancer in the film. Imaging with a fluorescence laser microscope indicated the ability of the optimized film to deliver the payload to deeper skin layers. Furthermore, optimized AVA-loaded TPGS-micelles film showed a significant increase (p < 0.05) in the Cmax of AVA and the area under the AVA plasma curve (approximately three-fold). The optimized AVA-loaded TPGS-MM film thus represents a successful delivery system for enhancing the bioavailability of AVA.

Gaikwad Abhijeet R. Phytosome as a Novel Drug Delivery System for Bioavailability Enhancement of Phytoconstituents and its Applications: A Review

Phytoconstituents are used extensively in modern science due to their varied therapeutic actions with few side effects. Regardless of their excellent pharmacodynamic activity, many Phytoconstituents have shown less bioavailability in vivo. Novel drug delivery systems have gained vital importance due to their increased bioavailability, and overall therapeutics. The water miscible Phytoconstituents have excellent bioactivity in vitro, however poor or no action in vivo. Phytosome technology can overcome this drawback during which the Phyto actives are allowed to react with phospholipid molecules. The Phytoconstituents with low lipoid solubility on complexation into herbal extract. Phospholipids show high affinity for polyphenolics, and type supramolecular adducts having a certain ratio. Hydrogen bond interactions between Phytoconstituents and phospholipids enable phospholipid complexes as an integral part. Complexation of phospholipids with active constituents of plants improves their bioavailability and is being extensively studied by researchers, and additional research during this regard is predicted within the future. This review highlights the unique property of phospholipids in drug delivery, phospholipid chemistry, stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, advantages, recent patents, marketed formulation their application to enhance the bioavailability of active herbal Phytoconstituents. Keywords: Phytosome, Novel drug delivery, Phosphatidylcholine, Bioavailability, Patents, Applications.

Enhancement of Dissolution Rate and Bioavailability of Nifedipine by Chitosan Based Cocrystallization Technique

The objective of present study was to enhance solubility and dissolution behaviour of nifedipine by using cocrystallization method. A significant increase in solubility and dissolution rate of nifedipine has been demonstrated by solvent change method using chitosan. In this method, chitosan was precipitated on nifedipine crystals using sodium citrate as a salting out agent. An accurately weighed chitosan was dissolved in 1% acetic acid and drug was added in the chitosan solution. This resulting solution was added drop wise into 1% sodium citrate solution with continuous stirring. Sodium citrate precipitate polymer on drug crystals. FTIR, DSC, XRD, SEM, In-vitro dissolution studies, were studied for characterization of prepared cocrystals. Stability studies showed a good stability character of prepared cocrystals. Design Expert® software version 10.0 was used to develop polynomial models which were analysed to delineate the main effects for each CQA (critical quality attributes) through Box-Bhenken design expert. Pharmacokinetic study clearly showed the enhancement of dissolution rate of cocrystals. The above investigation concluded that the significant dose reduction is possible for nifedipine with cocrystal formulation which leads to improve patient compliance.

Preparation, Characterization and Optimization of Irbesartan Loaded Solid Lipid Nanoparticles for Oral Delivery

The purpose of this study was to develop and evaluate irbesartan (IS) loaded solid lipid nanoparticles (SLNs; IS-SLNs) that might enhance the oral bioavailability of IS. IS, an angiotensin-receptor antagonist, used to treat hypertension. However, poor aqueous solubility and poor oral bioavailability has limited therapeutic applications of IS. Components of the SLNs include either of trimyristin/tripalmitin/tristearin/trilaurate/stearic acid/beeswax, and surfactants (Poloxamer 188 and soylecithin). The IS-SLNs were prepared by hot homogenization followed by ultrasonication method and evaluated for particle size, poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), drug content and in vitro drug release. The physical stability of optimized formulation was studied at refrigerated and room temperature for two months. The optimized IS-SLN formulation (F4) had a mean diameter of about 217.6±3.62 nm, PDI of 0.163±0.032, ZP of -28.5±4.12, assay of 99.8±0.51 and EE of 93.68±2.47%. The formulation showed sustained drug release compared with control formulation over 24 h. Optimized formulation was found to be stable over two months. IS-SLN showed nearly spherical in shape using and converted to amorphous form by DSC. Thus, the results conclusively demonstrated SLNs could be considered as an alternative delivery system for the oral bioavailability enhancement of IS.

The effect of drug loading on the properties of abiraterone–hydroxypropyl beta cyclodextrin solid dispersions processed by solvent free KinetiSol® technology

Abiraterone is a poorly water-soluble drug used in the treatment of prostate cancer. In our previous study, we reported that KinetiSol® processed solid dispersions (KSDs) based on hydroxypropyl β-cyclodextrin (HPBCD) showed improved dissolution and pharmacokinetics of abiraterone. However, the nature of abiraterone-HPBCD interaction within the KSDs or the effect of drug loading on the physicochemical properties and in vivo performance of HPBCD-based KSDs remain largely unknown. We hypothesize that KinetiSol technology can prepare abiraterone-HPBCD complexes within KSDs and that increasing the drug loading beyond an optimal point reduces the in vitro and in vivo performance of these KSDs. To confirm our hypothesis, we developed KSDs with 10–50% w/w drug loading and analyzed them using X-ray diffractometry and modulated differential scanning calorimetry. We found that KSDs containing 10–30% drug were amorphous. Interestingly, two-dimensional solid-state nuclear magnetic resonance and Raman spectroscopy indicated that the abiraterone-HPBCD complexes were formed. At elevated temperatures, the 10% and 20% drug-loaded KSDs were physically stable, while the 30% drug-loaded KSD showed recrystallization of abiraterone. In vitro dissolution and in vivo pharmacokinetic performances improved as the drug loading decreased; we attribute this to increased noncovalent interactions between abiraterone and HPBCD at lower drug loadings. Overall, the 10% drug loaded KSD showed a dissolution enhancement of 15.7-fold compared to crystalline abiraterone, and bioavailability enhancement of 3.9-fold compared to the commercial abiraterone acetate tablet Zytiga®. This study is first to confirm that KinetiSol, a high-energy, solvent-free technology, is capable of forming abiraterone-HPBCD complexes. Furthermore, in terms of in vitro and in vivo performance, a 10% drug load is optimal.

Interactions between Humic Substances and Microorganisms and Their Implications for Nature-like Bioremediation Technologies.

The state of the art of the reported data on interactions between microorganisms and HSs is presented herein. The properties of HSs are discussed in terms of microbial utilization, degradation, and transformation. The data on biologically active individual compounds found in HSs are summarized. Bacteria of the phylum Proteobacteria and fungi of the phyla Basidiomycota and Ascomycota were found to be the main HS degraders, while Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were found to be the predominant phyla in humic-reducing microorganisms (HRMs). Some promising aspects of interactions between microorganisms and HSs are discussed as a feasible basis for nature-like biotechnologies, including the production of enzymes capable of catalyzing the oxidative binding of organic pollutants to HSs, while electron shuttling through the utilization of HSs by HRMs as electron shuttles may be used for the enhancement of organic pollutant biodegradation or lowering bioavailability of some metals. Utilization of HSs by HRMs as terminal electron acceptors may suppress electron transfer to CO2, reducing the formation of CH4 in temporarily anoxic systems. The data reported so far are mostly related to the use of HSs as redox compounds. HSs are capable of altering the composition of the microbial community, and there are environmental conditions that determine the efficiency of HSs. To facilitate the development of HS-based technologies, complex studies addressing these factors are in demand.

A Review on Novel vesicular systems for enhanced Oral bioavailability of Lipophilic drugs

The poor oral bioavailability of many drugs is mainly due to the poor aqueous solubility, chemical instability and pre-absorptive metabolism. Numerous approaches have been developed for enhancement of oral bioavailability and were currently in the clinical application. Even though, some drugs not meet the required clinical application due to the patient compliance and ineffective therapeutic levels. Vesicular delivery systems are considered as alternative delivery for the enhancement the bioavailability of this category of drugs. The enhanced bioavailability of the liphophilic drugs from the vesicular systems mainly due to the increased effective surface area of the drug in the presence of lipids, surfactants and co surfactants, enhanced lymphatic uptake, altered gastric motility and by virtue of their small particle size. Extensive literature is available for the properties, applications, and preparation and evaluation methods. This review mainly dealt with the reported drug loaded various vesicular systems such as liposomes, niosomes, lipid nanoparticles, self-emulsifying delivery system, nanosuspensions.

A study to enhance the oral bioavailability of s-adenosyl-l-methionine (SAMe): SLN and SLN nanocomposite particles

The endogenous molecule, S-adenosyl-l-methionine (SAMe) is a key factor due to its role in the methylation cycle and modulation of monoaminergic neurotransmission. Since many mental disorders have linked to the monoaminergic system, the level of SAMe in blood and cerebrospinal fluid is important in the treatment of major depression. In this study, solid lipid nanoparticles (SLN) were prepared in order to increase the limited oral bioavailability of SAMe, and SLN based nanocomposite particles (SAMe-SLN-NC) were further developed using an enteric polymer for passive targeting of intestinal lymphatic system. In this manner, it was also aimed to protect SAMe loaded SLN from harsh gastric environment as well as hepatic first-pass metabolism. Dynamic light scattering (DLS) analysis of SLN was performed, drug content was measured, SAMe release patterns were examined and the permeation ability of SAMe was investigated by the Parallel Artificial Membrane Permeability Assay (PAMPA) to characterize SAMe loaded SLN formulation. According to the PAMPA results, SAMe-SLN with the average particle size of 242 nm showed enhanced SAMe permeability in comparison to pure drug. Delayed drug release obtained by SLN nanocomposite particles indicated the protection of drug-loaded SLN in the acidic gastric medium and their intact presence in the intestine. SAMe solution or particle suspensions were prepared using 0.45 (w/v) hydroxypropyl methylcellulose aqueous solution to be applied to groups of animals for pharmacokinetic studies. In vivo pharmacokinetic parameters revealed enhancement in relative bioavailability of SAMe upon oral administration of SLN based formulations. This was attributed to intact absorption of lipid matrix through lymphatic path. A statistically significant increase in SAMe plasma levels was obtained at 15th and 30th minutes with SAMe-SLN and at 2nd and 4th hours with SAMe-SLN-NC.Overall results suggest that SLN is a promising carrier to passive lymphatic targeting of SAMe and novel SLN nanocomposite particles which presented efficient oral bioavailability is a potential way for oral delivery of SAMe and treatment of major depression.

Pharmacokinetic evaluation of the synergistic effect of raloxifene loaded transfersomes for transdermal delivery

The current research work involves the comparative evaluation of the synergistic potential of transfersomes with span 80, span 85 for transdermal delivery of raloxifene hydrochloride (RXN). The prepared transfersomes were optimised using size, entrapment efficiency, transdermal flux, and further characterised for other physicochemical properties. The fate of the drug within the lipid vesicles was investigated by differential scanning calorimetry and X-rays diffraction. Morphology, shape and 3-D structure was evaluated using electron microscopy. 31PNMR was carried out to evaluate the formation of lipid bilayers in the prepared vesicles. Vesicles size were found in the range of 90–140 nm with particle size and acceptable zeta potential. The transdermal flux of synergistic transfersomes (TSP-80 + 85) was much higher when compared with individual span 80 and span 85 based transfersome formulations. On the comparative evaluation of bioavailability in a rat model with transfersomal gel, oral tablet solution and hydroethanolic gel of active drug revealed that TSP-80 + 85-5 had a significant enhancement in the transdermal bioavailability in contrast to the other formulations. The study provided new insight into synergistic use of surfactants for transfersomes with successful transdermal delivery and bioavailability enhancement of poorly soluble and high metabolic rate drugs like raloxifene hydrochloride.

Cyclodextrin Based Nanosponges: A Multidimensional Drug Delivery System and its Biomedical Applications.

Cyclodextrin based nanosponges are the designed nanocarriers for the projected delivery of complex drugs. They are multifunctional hypercrosslinked cyclodextrin polymers connected in a three-dimensional, mesh-like network. Their functional characteristics can be fabricated by using different crosslinkers or their different rations with polymer. They can encapsulate various hydrophilic, lipophilic, small-sized or large-sized drug molecules. They offer formulation flexibility and are primarily used for solubility, bioavailability and stability enhancement purposes. This system is also pliable for co-delivery of pharmaceutical entities, improving therapeutic efficacy and patient compliance. If the surface of nanosponge is coupled with an appropriate ligand, even a target specific drug delivery can be achieved. It has a variety of applications in the field of pharmacy for the delivery of tricky drug molecules, proteins, enzymes, natural moieties and gaseous compounds. The list of its applications further widens with the development of nanodiagnostics, nanosensors, biomimetics and scaffolds based on nanosponges. The sudden explosion of research in this working area signifies cyclodextrin nanosponge based products in the market soon.

Phytochemical Investigation and Spectrophotometric Studies of Piperine and Thymoquinone Compounds in Methanolic Extracts of Nigella sativa and Piper nigram spices

This study was carried out on some spice samples including Nigella sativa and Piper nigram. Phytochemical screening was applied to the methanolic extraction of both the studied plants. The results showed that methanolic extract of Nigella sativa and Piper nigram revealed the presence of various chemical constituents, such as Alkaloide, Carbohydrates, Glycosides, Tannins, Flavones, Saponins. Piperine is characterizing compound present in fruits of piper nigram used as a bioavailability enhancer. Some spectrophotometric methods as (U.V) and I.R were applied to identify the major chemical compounds of the studied extracts. The results recorded that the Piperine and Thymoquinone compounds were found in the studied plant extracts. Keywords: Piper Nigram, Nigella sativa, Piperine Thymoquinone, Spectrophotometric

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.

Revealing Changes in Curcumin Bioavailability using Vitamin C as an Enhancer by HPLC-MS/MS

Background: Curcumin (CUR), a natural isolated compound from turmeric, helps in fighting many diseases, but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through coadministration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by highperformance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C18 reverse-phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 &gt; 216.7 for curcumin and m/z 265.2 &gt; 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters, including the growth of AUC (0-t) up to 2.4 times, a 2.2- fold increase of Cmax, 2.2-fold loss of CL, and 1.5-fold diminishment of t1/2. Conclusion: An HPLC-ESI-MS/MS method for the determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C was determined. These changes were reasoned to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

Attenuation of lipid levels in triton induced hyperlipidemia rats through rosuvastatin calcium nanoparticles: Pharmacokinetic and pharmacodynamic studies

The aim of this research was to study the effect of marketed tablet (Crestor®) powder suspension (MTPS) and nanoparticle formulation of rosuvastatin calcium (RC) on the pharmacokinetic (PK) and pharmacodynamic (PD) parameters in hyperlipidemia rats. The hyperlipidemia is induced by intraperitoneal injection of Triton-X-100 in 0.9 %w/v saline solution. The marketed tablet was dispersed into suspension. The RC loaded nanoparticles (RC-NPs) are prepared by homogenization method. The prepared RC-NP formulation was characterized for size, drug excipient compatibility and crystallization by differential scanning calorimeter (DSC), morphology by SEM, stability at room temperature, in-vitro dissolution and in-situ absorption in rats. Further, the pharmacokinetic and pharmacodynamic studies were conducted in hyperlipidemia rats. The size of the RC-NP formulation was found to be 183.4 ± 4.5 nm and to be nearly spherical by SEM. DSC studies revealed that no interaction and RC converted to amorphous form in RC-NP formulation. RC-NP formulation was physically and chemically stable over two months at room temperature. The drug release was found to be 25.8 ± 2.5 and 89.96 ± 2.8 % in five mins, respectively from MTPS and RC-NP formulations. The Peff of MTPS and NP of RC was 1.8 ± 0.2 × 10−5 and 2.7 ± 0.3 × 10-5 cm/s, respectively. From the PK studies, the enhancement in the oral bioavailability was found to be 2.4-folds when compared to MTPS formulation and statistically significant (p < 0.05). PD study of RC-NP formulation in hyperlipidemic rats exhibited decrease in lipid profile for 24 h, while MTPS exhibited a decrease in lipid profile for 12 h. Therefore, the results conclusively demonstrate the nanoparticles of RC showed significant enhancement in the PK and PD parameters.