Anionic Drugs Research Articles

Ubiquitin-specific peptidase 8 regulates the trafficking and stability of the human organic anion transporter 1

BackgroundOrganic anion transporter 1 (OAT1) plays a vital role in avoiding the potential toxicity of various anionic drugs through the involvement of kidney elimination. We previously demonstrated that ubiquitin conjugation to OAT1 led to OAT1 internalization from cell surface, followed by degradation. Ubiquitination is a dynamic process, where deubiquitination is catalyzed by a class of ubiquitin-specific peptidases.MethodsThe role of ubiquitin-specific peptidase 8 (USP8) in hOAT1 function, expression and ubiquitination was assessed by conducting transporter uptake assay, biotinylation assay and ubiquitination assay.ResultsWe demonstrated that USP8 overexpression in hOAT1-expressing cells led to an increased hOAT1 transporter activity and expression, which correlated well with a reduced hOAT1 ubiquitination. Such phenomenon was not observed in inactive USP8 mutant-transfected cells. In addition, the knockdown of endogenous USP8 by USP8-specific siRNA resulted in an increased hOAT1 ubiquitination, which correlated well with a decrease in hOAT1 expression and transport activity. Biotinylation experiments demonstrated that USP8-induced increase in hOAT1 expression and transport activity occurred through a deceleration of the rates of hOAT1 internalization and degradation.ConclusionsThese results indicated the regulatory role of USP8 in OAT1 function, expression, trafficking, and stability.General significanceUSP8 could be a new target for modulating OAT1-mediated drug transport.

Conductive poly(2-ethylaniline) dextran-based hydrogels for electrically controlled diclofenac release.

Transdermal drug delivery systems (TDDS) are used as an alternative route to deliver drugs into the blood system for therapy. The matrix materials that have been widely used in TDDS are hydrogels. The dextran hydrogels were prepared by the solution casting using trisodium trimetaphosphate (STMP) as the crosslinking agent, and diclofenac sodium salt (Dcf) as the anionic model drug. Poly(2-ethylaniline) (PEAn) was successfully synthesized and embedded into the dextran hydrogel as the drug encapsulation host. The in-vitro release of Dcf from the hydrogels was investigated using a modified Franz-Diffusion cell in a phosphate-buffered saline (PBS) solution at the pH of 7.4 and at 37°C for a period of 24h, under the effects of crosslinking ratios, dextran molecular weights, electric potentials, and the conductive polymer PEAn. The release mechanism of Dcf from the dextran hydrogels and the composite without electrical potential was the diffusion controlled mechanism or the Fickian diffusion. Under applied electrical potentials, the release mechanism was a combination between the Fickian diffusion and the matrix swelling. The Dcf diffusion coefficients from the dextran hydrogels without electrical potential increased with decreasing crosslinking ratio and molecular weight. Under electrical potentials, the corresponding diffusion coefficients were much higher due mainly to the electro-repulsive force between the negatively charged electrode and the negatively charged dextran and the induced dextran expansion. For the Dcf-loaded PEAn/dextran composite, the diffusion coefficient was enhanced by two orders of magnitude when the electric potential was applied, specifically illustrating the unique features of PEAn as an efficient drug encapsulation host without electric field, and as a drug release enhancer under electric field through the reduction reaction.

A simple desolvation method for production of cationic albumin nanoparticles with improved drug loading and cell uptake

The transport protein albumin has been used as a drug nanocarrier for a long time due to its versatility. Albumin is negatively charged at physiological conditions limiting its anionic drug loading capacity. However, loading of anionic drugs in the albumin nanoparticles (NPs), can be facilitated by albumin cationization. Here, we postulate a simple desolvation method for preparation of cationic albumin NPs with improved anionic drug loading. First, bovine serum albumin was cationized with ethylenediamine. Next, salicylic acid (SA) was added to the cationic bovine serum albumin (cBSA) solution prior to the desolvation. Among different desolvating agents tested, acetonitrile allowed the highest nanoparticle formation yield. The SEM analyses showed that the average size of cBSA NPs decreased from ~200 nm to ~100 nm upon SA loading. Moreover, the drug loading capacity of cBSA NPs was found to increase ~2 fold, and drug release was slower compared to BSA NPs. Finally, a significant increase in cellular uptake of cBSA NPs compared to that of native BSA NPs showed the potential for improved drug delivery.

Extended delivery of cationic drugs from contact lenses loaded with unsaturated fatty acids

This paper describes the use of surface-active anionic unsaturated fatty acids in commercial contact lenses to extend drug release duration and regulate delivery dosage. We studied the effect of oleic acid on the in vitro release kinetics of three cationic drugs, and two anionic drugs from silicone hydrogel contact lenses. The release duration of the cationic drugs: tetracaine hydrochloride, bupivacaine hydrochloride, and ketotifen fumarate was significantly extended from less than a day to more than a month because of the presence of oleic acid in the contact lenses. With a simple change in the fatty acid loading media, we could duplicate a similar efficacy by loading oleic acid in conventional non-silicone hydrogel contact lenses. The fitted effective diffusivity values of the three cationic drugs significantly decrease when the oleic acid weight % in the lenses is increased. By using two other unsaturated fatty acids, linoleic and α-linolenic acid, the release duration of ketotifen fumarate was also significantly extended in silicone hydrogel contact lenses. In contrast, the release of two anionic drugs, diclofenac sodium and flurbiprofen sodium, was accelerated for oleic acid modified lenses. These results show the dominating impact of coupling charge interactions between the drug and the fatty acid carrier molecules to precisely adjust delivery rate and dosage from a contact lens.

β-Glycerol phosphate/genipin chitosan hydrogels: A comparative study of their properties and diclofenac delivery

Thermosensitive hydrogels based on polysaccharides are suitable candidates for the design of biodegradable and biocompatible injectable drug delivery systems. Thus, the combination of chitosan (CHI) and β-glycerol phosphate disodium salt (β-GP) has been intensively investigated to develop thermo-induced physical gels. With the aim of exploring the possibilities of optimization of these hydrogels, in this work, chitosan, β-GP and naturally extracted crosslinking agent, genipin (GEN), have been successfully combined, obtaining co-crosslinked hydrogels with both in situ physical and covalent crosslinking. A wide range of β-GP concentrations have been selected in order to analyze its influence on a variety of properties, including gelation time, pore size, water uptake ability, in vitro hydrolytic and enzymatic degradation, mucoadhesion and mechanical and rheological properties. Furthermore, the potential application of the developed systems for the administration and controlled release of an anti-inflammatory anionic drug, such as diclofenac, has been successfully demonstrated.

Cationic polyelectrolyte grafted mesoporous magnetic silica composite particles for targeted drug delivery and thrombolysis

Magnetic iron oxide (Fe3O4) microparticles prepared by solvothermal route are modified with SiO2 layer and then functionalized with vinyl groups. Finally, polyelectrolyte layer composed of isobornyl methacrylate (iBMA) and (3-acrylamidopropyl)trimethylammonium chloride (APTMACl) is grafted onto the surface of magnetic SiO2 particles via free radical polymerization to produce composite particles abbreviated as Fe3O4/SiO2/P(iBMA-APTMACl). The size distribution and structural composition of Fe3O4/SiO2/P(iBMA-APTMACl) composite particles are measured by electron microscopy and different spectroscopy techniques. Fe3O4/SiO2/P(iBMA-APTMACl) composite particles possessed moderate paramagnetic property. The mesoporous surface structure of composite particles is confirmed from average pore diameter (3.8 nm), measured by Barrett–Joyner–Halenda (BJH) method. The composite particles exhibited pH dependent phase transition near 5.8. The pH dependent adsorption and release study of anionic drug (aspirin) through off- and on-capping of polyelectrolyte valve/gate confirmed the ion exchange property of Fe3O4/SiO2/P(iBMA-APTMACl) composite particles. Compared to Fe3O4/SiO2 particles, the loading capacity of biomolecules in polyelectrolyte grafted composite particles (∼ 30 mg g−1) is relatively larger at the respective isoelectric point. In presence of 11.2 kU mg−1 conjugated streptokinase (SK), Fe3O4/SiO2/P(iBMA-APTMACl) composite particles exhibited significant amount of thrombolytic activity (56%). A brief study of hemolysis suggested that composite particles are hemocompatible up to 0.18 mg mL−1. The higher inhibition percentage of protein denaturation also indicated the anti-inflammatory property of bare composite particles. The prepared Fe3O4/SiO2/P(iBMA-APTMACl) composite particles can therefore be applied in targeted thrombolysis, drug/gene carrier, anti-inflammatory agent and hyperthermia.

Acamprosate Is a Substrate of the Human Organic Anion Transporter (OAT) 1 without OAT3 Inhibitory Properties: Implications for Renal Acamprosate Secretion and Drug-Drug Interactions.

Acamprosate is an anionic drug substance widely used in treating symptoms of alcohol withdrawal. It was recently shown that oral acamprosate absorption is likely due to paracellular transport. In contrast, little is known about the eliminating mechanism clearing acamprosate from the blood in the kidneys, despite the fact that studies have shown renal secretion of acamprosate. The hypothesis of the present study was therefore that renal organic anion transporters (OATs) facilitate the renal excretion of acamprosate in humans. The aim of the present study was to establish and apply OAT1 (gene product of SLC22A6) and OAT3 (gene product of SLC22A8) expressing cell lines to investigate whether acamprosate is a substrate or inhibitor of OAT1 and/or OAT3. The studies were performed in HEK293-Flp-In cells stably transfected with SLC22A6 or SLC22A8. Protein and functional data showed that the established cell lines are useful for studying OAT1- and OAT3-mediated transport in bi-laboratory studies. Acamprosate inhibited OAT1-mediated p-aminohippuric acid (PAH) uptake but did not inhibit substrate uptake via OAT3 expressing cells, neither when applied concomitantly nor after a 3 h preincubation with acamprosate. The uptake of PAH via OAT1 was inhibited in a competitive manner by acamprosate and cellular uptake studies showed that acamprosate is a substrate for OAT1 with a Km-value of approximately 700 µM. Probenecid inhibited OAT1-mediated acamprosate uptake with a Ki-value of approximately 13 µM, which may translate into an estimated clinically significant DDI index. In conclusion, acamprosate was identified as a substrate of OAT1 but not OAT3.

Design of 3D multi-layered electrospun membranes embedding iron-based layered double hydroxide for drug storage and control of sustained release

Nowadays polymer dressings are expected to possess multiply functions. Besides acting as physical barriers, dressings may provide for the injured tissue species able to turn wound healing process faster and painless. In this way, dressings can be designed aiming to enable the release of drugs. The possibility to modulate drug release kinetics is a desired characteristic to be achieved in order to turn drug delivery systems adequate to specific treatments. However, hydrophilic drugs and hydrophobic polymers incompatibility hinders such modulation and a long-term release cannot be achieved efficiently. Here we present the design of poly(lactic acid) (PLA) membranes containing iron-based Layered Double Hydroxide (LDH) particles able to storage a hydrophilic anionic drug (derived from the non-steroidal anti-inflammatory naproxen). LDH particles are excellent candidates to compose multifunctional composites. They may present diverse biocompatible compositions, possess an elevated encapsulation capacity and tends to promote drugs sustained release by its own, besides assisting tissues regeneration process. Nanofibrous membranes were prepared by the combination of electrospun PLA and electrosprayed LDH as alternated layers (approach A) and also by both technics performed at the same time (approach B). In approach A, by varying the thickness of the PLA fibrous layers, it was possible to easily modulate the drug release rate. Half of drug content was released after 1, 4 and 17 days for the membranes containing the thinnest, the intermediate and the thicker PLA layers, respectively, and after 56 h for the membrane prepared by the approach B. Naproxen release was kept for 18 days for the thinnest membrane, 59 days for the membrane prepared by the approach B and 66 days for the thicker membranes. We believe that this work can inspire the development of new functional membranes with tunable drug release profile thanks to the versatile electrospinning and electrospraying techniques.

Durable nanofibrous matrices augmented with hydrotalcite-like compounds for cutaneous regeneration of burn wounds

Electrospinning of Gelatin (G) and Poly-3-hydroxybutyric acid (P) incorporated with anionic drug (AgSD) loaded hydrotalcite (L) (L-AgSD) is carried out to fabricate a nanofibrous scaffold which would recreate the native extracellular matrix suitable for cutaneous regeneration. The L-AgSD complex was augmented into electrospun nanofibers of diameter 100–140 nm. The physiochemical (XRD, FTIR), morphological (SEM), mechanical (tensile strength) and biological (in vitro and in vivo) properties of the developed wound construct were studied. Antimicrobial studies reveal the potential activity against microbial infection. Studies on drug release kinetics demonstrate a controlled release of 86% in 72 h. In vitro biocompatibility studies using NIH 3T3 fibroblast cell line showed excellent cell adhesion and cell proliferation indicating the biocompatible nature of the scaffold. The matrix accelerated wound healing on Pseudomonas infected burn wound induced on rat models. The tailored matrix is promising as an impending nanohybrid construct for burn wound injuries with controlled drug release and antibacterial activity.

Eudragit RL-based film coatings: How to minimize sticking and adjust drug release using MAS

Polymeric film coatings based on quaternary polymethacrylates (QPMs, e.g. Eudragits®) are frequently used for controlled release applications. However, their considerable sticking tendency is a major drawback in practice. In this study, different amounts of magnesium aluminum silicate (MAS) were added to the film coatings in order to overcome this hurdle. MAS is negatively charged and can electrostatically interact with the positively charged QPM. Different types of tablet cores were coated with aqueous Eudragit® RL 30D dispersions, optionally containing varying amounts of MAS. Dynamic changes in the wet mass of the systems as well as drug release upon exposure to 0.1 M HCl and phosphate buffer pH 6.8 were monitored. Propranolol HCl, acetaminophen, and diclofenac sodium were used as cationic, nonionic and anionic model drugs. The tablets were optionally cured for 12 h at 45 or 60 °C. Importantly, the addition of MAS to aqueous Eudragit® RL 30D dispersion substantially reduced the films’ stickiness and led to stable inner coating structures, even without curing. Desired drug release rates can be adjusted by varying the QPM:MAS ratio and coating level.

Versatile grafted microcrystalline cellulose with ionic liquid as new Losartan-controlled release material

This paper describes the preparation and characterization of a versatile Losartan-controlled-release material based on a functionalized cellulosic matrix grafted with the ionic liquid, [(MeO)3Sipmim][Cl]: 1–(trimethoxysilylpropyl)–3–methylimidazolium Chloride. A silanized ionic liquid was used as a solvent and a surface modification agent at the same time, allowing higher anionic drug loading capacity. The anionic Losartan drug release kinetics were evaluated as a model. The Losartan release was made using two distinct media, one at pH 7.4 and the other at 3.0 to simulate blood and stomach pH, respectively. Higher Losartan release-rate 88% at blood pH after 1085 min in comparison with 84% at stomach pH, after 330 min was attained. The higher Losartan release profile in acid pH compared with neutral pH could be associated to the hydrolysis of Si-O bond from the ionic liquid, with the acidic medium acting as a catalyst. This cellulosic matrix modified with ionic liquid showed promising for applications over a wide range of pH-controlled-release systems.

Poly(Ethylene Glycol) Crosslinked Multi-Armed Poly(l-Lysine) with Encapsulating Capacity and Antimicrobial Activity for the Potential Treatment of Infection-Involved Multifactorial Diseases.

With the development of modern medical technology, common diseases usually can be treated by traditional medicines and their formulation, while diseases with multiple etiologies still remain a great challenge in clinic. Nanoformulation was widely explored to address this problem. However, due to limited drug loading space of nanocarriers, co-delivery strategy usually fails to achieve sufficient loading of multiple drugs simultaneously. In this research, we explored the potential of poly(ethylene glycol) (PEG) crosslinked alternating copolymers MPLL-alt-PEG as both an anionic drug carrier and antimicrobial agent. The high cationic charge density of multi-armed poly(l-lysine) (MPLL) segments in MPLL-alt-PEG could endow the electrostatic encapsulation of anionic model drugs through the formation of polyion complex micelles with a MPLL/drug complex core and crosslinked PEG outer shell, enabling pH-sensitive drug release. Meanwhile, the MPLL-alt-PEG copolymer exhibits a broad spectrum of antimicrobial activities against various clinically relevant microorganisms with low hemolytic activity. Studies on antibacterial mechanism revealed that MPLL-alt-PEG attacked bacteria through the membrane disruption mechanism which is similar to that of typical antimicrobial peptides. Taken together, the present study shed light on the possibility of endowing a polymeric carrier with therapeutic effect and thus offered a promising strategy for achieving a comprehensive treatment of bacterial infection-involved multifactorial diseases.

Chitosan surface modified hydrogel as a therapeutic contact lens

Therapeutic contact lenses have attracted significant attention during the last decades. In this study, we used chitosan‐conjugated poly(2‐hydroxyethyl methacrylate) (PHEMA) for contact lens application. We aimed to increase affinity of anionic drugs, which are used in treatment of eye diseases. In this regard, we evaluated delivery of the small molecule anionic drug, ascorbic acid from the chitosan‐conjugated PHEMA. Chitosan immobilization improves drug loading efficiency and induces sustained release of ascorbic acid. The chitosan modified hydrogel also reduces the biofouling of tear fluid components. Our results showed that surface modification by chitosan inhibits protein and bacterial deposition on the contact lens. Protein absorption analysis revealed that neat PHEMA adsorbed tear proteins at a density of 28.4 ± 4.4 μg/cm2, whereas the chitosan‐conjugated hydrogel adsorbed tear proteins at a density of 18.5 ± 1.8 μg/cm2. Moreover, the neat PHEMA bacterial adhesion had a mean CFU value of 273 ± 27. However, a significant decrease in the number of bacterial colonies was observed in the chitosan group with a CFU value of 9 ± 6.

RECENT NANOCOCHLEATE DRUG DELIVERY SYSTEM FOR CANCER TREATMENT: A REVIEW

Nanocochleates are at the forefront of the fast-growing nanotechnology sector in the delivery of drugs for cancer. This nanotechnology is the use of the cationic and anionic encapsulated drug that has poor oral bioavailability. Nanocochleate is a lipid-based drug delivery in the liposomal vesicles that is converted by calcium divalent cation into nanocochleate. Nanocochleates technology use encapsulations of the anticancer agent, which have low solubility, oral bioavailability and low permeability. This paper shows and provides an overview of the benefits of nanocochleates, drug delivery mechanism, choice of prevalent components (Phospholipids and Cations), various ways of producing nanocochleates and nanocochleate stability. Nanocochleates have far fewer constraints than other traditional carriers. To characterize nanocochleates, the suitable analytical methods are required. Therefore, in the therapy of cancer, nanocochleate becomes commonly applied and more prospective drug delivery system.

Needle-like supramolecular amphiphilic assembly constructed by the host–guest interaction between calixpyridinium and methotrexate disodium

In this work, the host–guest interaction between calixpyridinium and the anionic anticancer drug methotrexate disodium was explored in water. Unexpectedly, an interesting anisotropic needle-like rather than an ordinary isotropic spherical supramolecular amphiphilic assembly was fabricated by the complexation of calixpyridinium with methotrexate disodium. It is the second anionic guest to be discovered to form the non-spherical supramolecular assembly upon complexation with calixpyridinium. This discovery implies the possibility to construct various topological nanostructures based on the host–guest interactions between calixpyridinium and the anionic drugs in the future. The resulting calixpyridinium–drug assemblies with different morphologies may have the diverse potentials to adjust the efficacies of anionic drugs.

Synthesis and surface modification of chitosan built nanohydrogel with antiviral and antimicrobial agent for controlled drug delivery

As hydrophobic drug carriers, chitosan (CS) and Starch (SR) were copolymerized as biodegradable nanohydrogel and were functionalized with pthalic-anhydride and hexamethylenetetramine via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide catalyzed coupling, respectively. The structure, morphology, physicochemical and drug loading performance of native and functioned hydrogel were investigated by using several characterization techniques. With the successive functionalization the significant properties like porosity increases and crosslinking density decreases due to the formation of hydrophilic contacts with aqueous solutions. The FESEM analysis revealed the hydrogel matrices with uniform particle size, porosity and deep pores with high internal surface area for extreme swelling and interacting with the drug and biomolecules for efficient drug administration. The effect of induced functionalities on the physicochemical performance and release of hydrophobic- anionic model drug (Bromocresol green) were studied at physiological conditions. The drug release capability of the synthesized nanohydrogel was increased from 65% to 80% and 85% by successive functionalization. The drug administration in selective hydrogel was not significant, presumably due to stronger H-bonding and entanglement within the system which was finely tuned by the induced hydrophilic, flexible and biocompatible functionalities in term of extended interfaces for the drug solutions. The physicochemical and electrokinetic performances suggested the selective hydrogel as promising carriers for the hydrophobic- anionic drugs at physiological conditions.

Monitoring diclofenac adsorption by organophilic alkylpyridinium bentonites.

Organoclays have been applied as efficient adsorbents for pharmaceutical pollutants from aqueous solution. In this work, dodecylpyridinium chloride (C12pyCl) and hexadecylpyridinium chloride (C16pyCl) cationic surfactants were used for the preparation of organobentonites destined for diclofenac sodium (DFNa) adsorption, an anionic drug widely detected in wastewater. The organofunctionalization of the clay samples was performed under microwave irradiation at 50 °C for 5 min with surfactant amounts of 100% and 200% in relation to the cation exchange capacity (CEC) of the pristine bentonite. The amount of incorporated ammonium salts based on CHN elemental analysis was higher for all samples prepared with 200% of the CEC. The basal spacings of the organoclays ranged from 1.54 to 2.13 nm, indicating the entrance of organic cations into the interlayer spacing of the clay samples, and the spacing depended on the size of the alkyl organic chain. The hydrophobic character of the organobentonites was verified by thermogravimetry and infrared spectroscopy (FTIR). The adsorption isotherms showed that the drug capacity adsorption was influenced by the amount of surfactant incorporated into the bentonite, the packing density and the arrangement of the surfactants in the interlayer spacing. Zeta potential measurements of the organobentonites and FTIR analysis after drug adsorption suggested that electrostatic and nonelectrostatic interactions contributed to the mechanism of adsorption.

A self-powered battery-driven drug delivery device that can function as a micromotor and galvanically actuate localized payload release

Most drug delivery vehicles lack thrust that propels them to disease sites for payload delivery. Herein, a microrod comprising a zinc (Zn) core and a positively-charged poly(3,4-ethylenedioxythiophene) (PEDOT+) shell incorporating an anionic model drug, which form a “galvanic cell” in an electrolyte solution, is proposed as a battery-driven drug delivery device. Upon immersion of the proposed Zn-based batteries in a physiological environment, two sets of redox reactions that compete with each other in a manner determined by the local pH occur spontaneously. At low pH, the reduction of H+ to H2 bubbles, which are essential to propel the Zn batteries as micromotors, prevails, while at higher pH, the reduction of PEDOT+ to actuate galvanically payload release dominates. Observations in mice suggest that the self-powered Zn batteries may rapidly react and move in the gastric fluid after oral administration, considerably improving their penetration and retention in the mucus layer for localized drug release, similar to those directly injected into the subcutaneous tissue. None of the investigated tissues exhibits any significant inflammation or cell apoptosis, revealing that the developed Zn-based batteries have potential to serve as safe drug delivery devices.

The inhibition mechanism of the uptake of lamivudine via human organic anion transporter 1 by Stellera chamaejasme L. extracts.

Stellera chamaejasme L. is a traditional Chinese medicine with a long history to treat stubborn skin ulcer, and it also has antiviral and antitumor effects. Neochamaejasmine B (NCB), Neochamaejasmine A (NCA) and Chamaechromone (CMC) are the major components in dried roots of Stellera chamaejasme L.. Our studies suggested that NCB, NCA and CMC are inhibitors of Organic anion transporter 1 (OAT1). OAT1 is encoded by solute carrier family 22 member 6 gene (SLC22A6) in humans and plays a critical role in the organic anion drug uptake and excretion in the kidney. Lamivudine is the typical substrate of OAT1 and is frequently used in combination with other antiviral drugs in clinical antiviral treatments. The aim of this study is to investigate the interaction and its mechanism between these bi-flavone components in Stellera chamaejasme L. and lamivudine via OAT1 both in vitro and in vivo. In vitro, the uptake studies in Madin-Darby canine kidney (MDCK) cells overexpressing OAT1 suggested that NCB inhibited the uptake of 6-CFL and lamivudine.Similar results were obtained for NCA and CMC. NCB was a noncompetitive and competitive inhibitor interaction with OAT1. IC50 values of NCB, NCA and CMC for inhibiting OAT1-mediated lamivudine transport were 2.46, 8.35 and 0.61 μmol·L-1, respectively. In vivo, the pharmacokinetic results of lamivudine in rats showed that the mean area under the plasma concentration-time curve (AUC0-∞) and maximal plasma concentration (Cmax) of lamivudine after co-administration is increased 2.94-fold and 1.87-fold, respectively, compared to lamivudine administration alone. The results of interactions between lamivudine and these bi-flavone components in Stellera chamaejasme L. extracts via OAT1 in vivo are consistent with studies in vitro. The inhibition of OAT1-mediated uptake of lamivudine by NCB, NCA and CMC is the possible mechanism for Stellera chamaejasme L. extracts improving the oral bioavailability of lamivudine in rats.

Sericin‐coated polymeric microfiltration membrane for removal of drug‐based micropollutants

AbstractBACKGROUNDDrug‐based micropollutants present in water sources are proven to be persistent, bioactive and toxic even at low concentration for human consumption. Therefore, the complete removal of the drugs from water is crucial to avoid long‐term medical complications. In the present study, a novel sericin‐coated adsorptive microfiltration (MF) membrane is used for the removal of drug‐based micropollutants.RESULTSThe sericin‐coated membrane was tested for removal of different classes of drugs from water. The membrane completely removed NSAIDs and antibiotics from water at 20 μg L−1 concentration. The adsorption mechanism was profoundly influenced by charge‐based interaction and hydrogen bonding, hence charged anionic drugs were more effectively removed than uncharged drugs. In multidrug mixtures, the removal efficiency was observed in the following sequence; ibuprofen > diclofenac > amoxicillin > ciprofloxacin > estrone > β‐estradiol. Desorption of the drugs from the membrane surface can be effectively controlled by altering the pH of the membrane‐cleaning solution. Presence of other inorganic salts in the aqueous drug solution did not interfere with the removal efficiency of the sericin‐coated membrane. The performance of sericin‐coated membrane was studied using continuous adsorptive membrane filtration approach. The dynamic adsorption behavior of a fixed‐bed membrane column was predicted using Bohart–Adams model. The model can predict the adsorption breakthrough curve with minimum experimental error.CONCLUSIONSThis study reveals the unique application of sericin‐coated MF membrane for effective removal of drug‐based micropollutants from water, and demonstrates its easy regeneration and effectiveness for multiple cycles of filtration. © 2019 Society of Chemical Industry