Ionic Liquid-salt Aqueous Two-phase System, a Novel System for theExtraction of Abused Drugs

A 1-butyl-3-methylimidazolium chloride-salt aqueous two-phase system was studied on extraction of abused drugs. The effects of sorts of salts, temperature, concentration of salt and drugs on system were investigated systematically. A satisfactory extraction efficiency of 93% was obtained for papaverine while that of morphine was 65%. The extraction mechanism was primarily discussed.

Aqueous Self-Assembly of Block Copolymers to Form Manganese Oxide-Based Polymeric Vesicles for Tumor Microenvironment-Activated Drug Delivery

Molecular self-assembly is crucially fundamental to nature.However,the aqueous self-assembly of polymers is still a challenge.To achieve self-assembly of block copolymers [(polyacrylic acid-block-polyethylene glycol-block-polyacrylic acid(PAA68-b-PEG86-b-PAA68)] in an aqueous phase,manganese oxide(MnO2) is first generated to drive phase separation of the PAA block to form the PAA68-b-PEG68-b-PAA68/MnO2 polymeric assembly that exhibits a stable structure in a physiological medium.The polymeric assembly exhibits vesicular morphology with a diameter of approximately 30 nm and high doxorubicin(DOX) loading capacity of approximately 94%.The transformation from MnO2 to Mn2+caused by endogenous glutathione(GSH)facilitates the disassembly of PAA68-b-PEG68-b-PAA68/MnO2 to enable its drug delivery at the tumor sites.The toxicity of DOXloaded PAA68-b-PEG68-b-PAA69/MnO2 to tumor cells has been verified in vitro and in vivo.Notably,drug-loaded polymeric vesicles have been demonstrated,especially in in vivo studies,to overcome the cardiotoxicity of DOX.We expect this work to encourage the potential application of polymer self-assembly.

Transdermal Drug Delivery by Electroporation： The Effects of Surfactants on Pathway Lifetime and Drug Transport

Electroporation creates aqueous pathways by short high-voltage pulses resulting in a transient perme- abilization of stratum corneum and an increase in the transdermal delivery rate.However the aqueous pathways will reseal after pulsing,which leads to the rapid drop of transdermal flux.In the present study,the surfactants were added to the donor solution to hinder the shrinkage and resealing of the electropore,and to prolong the lifetime of the aqueous pathways with the consideration that the surfactants could reduce the surface energy of the electropore. These effects of surfactants were demonstrated by the dynamic electrical resistance of the skin and the fluorescent imaging of the local transport regions.Piroxicam(PIX)was transported percutaneously in the presence of surfac- tants in vitro.Owing to the longer lifetime of aqueous pathways,together with the promotion of PIX availability at the barrier exterior and the improvement in the partition of PIX into the aqueous pathways,the presence of surfac- tants led to a remarkable increase in the transdermal delivery rate during electroporation and a significant growth of the accumulative transdermal amount of PIX.

Evaluation of Albuminated Curcumin as Soluble Drug Form to Control Growth of Cancer Cells <i>in Vitro</i>

Curcumin (Curc) is well known for its anticancer activity, but its poor solubility in aqueous medium is a major concern for little therapeutic outcome. Therefore, the effort to improve its bioavailability is a major research interest. The current study aimed at conjugation of Curc to serum albumin (Alb) to increase aqueous solubility of the former without affecting its drug action on cancer cell lines and primary cells in culture. Conditions for preparation of albumin-curcumin (Alb-Curc) conjugate were standardized to obtain pure and stable drug. The product was obtained in sufficient quantity to test its effect on cells in culture at different doses. Briefly, the conjugate was prepared by mixing Curc dissolved in DMSO with the Alb dissolved in phosphate buffered saline;conjugate was purified by gel filtration chromatography and was analyzed using UV-Vis spectroscopy for characteristic peaks of both molecules. The conjugate was added to culture medium to identify the effect of conjugate on cell cycling and apoptosis. Albuminated curcumin that showed 100-fold higher solubility than free Curc was stable and inhibitory to proliferation, induced cell cycle arrest and apoptosis. The conjugate showed apoptotic effects on endothelial cells indicating its anti angiogenic property. Primary fibroblast growth was also inhibited but at the higher dose. The in vitro results suggest that Alb-Curc which is free of insoluble native drug may find application in cancer therapy after appropriate in vivo evaluations.

Study on PEG-(NH_4)_2SO_4 Aqueous Two-Phase System and Distribution Behavior of Drugs

The distribution behavior of chlorpromazine hydrochloride (CPZ), procaine hydrochloride (PCN) and procaine amide hydrochloride (PCNA) in polyethylene glycol (PEG800 or PEG1500)-(NH4)2SO4 aqueous two-phase sys-tems has been investigated. The result shows that the PEG-(NH4)2SO4 aqueous two-phase system has potential ex-traction capability in small molecular drug separation. In PEG800-(NH4)2SO4 system, the extraction efficiencies (E) of CPZ, PCN and PCNA amount to 92.8%, 74.5% and 74.4%, respectively, with the distribution coefficients (KD) being 25.7, 5.9 and 5.8, correspondingly. In PEG1500-(NH4)2SO4 system, the extraction efficiencies (E) of CPZ, PCN and PCNA are 93.7%, 71.3% and 63.2%, respectively, with distribution coefficients (KD) of 39.6, 6.6 and 5.0, correspondingly. Based on the study on ultraviolet and fluorescence spectra and also distribution behavior of the drugs in PEG-(NH4)2SO4 aqueous two-phase system, extraction mechanism was further proposed that both hydro-gen bond and hydrophobic interaction are involved in extraction.

Emerging delivery systems based on aqueous two-phase systems:A review

The aqueous two-phase system(ATPS)is an all-aqueous system fabricated from two immiscible aqueous phases.It is spontaneously assembled through physical liquid-liquid phase separation(LLPS)and can create suitable templates like the multicompartment of the intracellular environment.Delicate structures containing multiple compartments make it possible to endow materials with advanced functions.Due to the properties of ATPSs,ATPS-based drug delivery systems exhibit excellent biocompatibility,extraordinary loading efficiency,and intelligently controlled content release,which are particularly advantageous for delivering drugs in vivo.Therefore,we will systematically review and evaluate ATPSs as an ideal drug delivery system.Based on the basic mechanisms and influencing factors in forming ATPSs,the transformation of ATPSs into valuable biomaterials is described.Afterward,we concentrate on the most recent cutting-edge research on ATPS-based delivery systems.Finally,the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.

The impact of a Wastewater Treatment Works in Southern Gauteng, South Africa on efavirenz and nevirapine discharges into the aquatic environment

There has been growing concern regarding the pollution of the aquatic environment with synthetic organic chemicals.Antiretroviral drugs,such as efavirenz and nevirapine,are pharmaceutical drugs and are referred to as emerging contaminants.Such drugs can be environmentally persistent and may be expected to pose potential risks to drinking water supplies.Sources of pharmaceutical drugs include effluents from Wastewater Treatment Works(WWTPs),hospital and pharmaceutical production facilities and the incorrect disposal of unused and expired medicines.Currently there are no monitoring programs and legislative guidelines for their regulations in South Africa.The aims of this study were firstly to develop a semi-quantitative method to extract and analyse efavirenz and nevirapine in the primary settling tank sludge.Secondly to use that method,and an existing method for liquid wastewater samples,to monitor the concentrations of efavirenz and nevirapine as the wastewater passes through the different stages of purification(anoxic;aerobic;pre and post chlorination)in the WWTP.This was repeated weekly over a period of 4 weeks.Thirdly,to determine if binding of efavirenz and nevirapine to the solids in the WWTP played a role in the removal of these compounds from the WWTP liquid phase.No references to the analysis of ARVDs in WWTP sludge were found in the literature.Grab samples of wastewater and sludge samples were collected from a WWTP(activated sludge treatment process)weekly for 4 weeks.Liquid samples were extracted solid phase extraction,solid samples were extracted using sonication followed by a QuEChERs clean-up.Sample extracts were then subjected to gas chromatography-time of flight mass spectrometry for analyte determination.Efavirenz concentrations entering the WWTP ranged between 5500 to almost 14000 ng/L.The removal of efavirenz by the WWTP ranged between 27 and 71%.The largest removal occurred in the anoxic zone,smaller amounts were removed in the aerators.Slight increases in efavirenz concentrations were found after chlorination and the final effluent into the river post maturation ponds again were slightly lower.Solids were found to contain efavirenz at concentrations between 17 and 43 mg/kg dried primary settling tank sludge and it is proposed that this binding to the solids is the main mechanism of removal of efavirenz from the wastewater stream as it passes through the WWTP.Although an order of magnitude lower nevirapine concentrations displayed the opposite behaviour and gradually increased through the various stages of purification in the WWTP.Minor fluctuations occurred but the concentrations of nevirapine were higher at the effluent(between 92 and 473 ng/L)than those entering the WWTP.No nevirapine was detected in the PST sludge.The increase in nevirapine concentrations are likely to be the result of the de-conjugation of the hydroxylated metabolites of nevirapine in the WWTP,its resistance to degradation and the lack of binding of the nevirapine to the PST sludge.