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    Study of freeze-dried quercetin-cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis. Pralhad Tayade,Rajendrakumar Kale Journal of pharmaceutical and biomedical analysis The inclusion behavior of 2-hydroxypropyl beta-cyclodextrin (HPbetaCD) and beta-cyclodextrin (betaCD), in solution and solid-state was studied towards a poorly water-soluble bioflavonoid, quercetin (QURC), chemically 3,3',4',5',7-pentahydroxy flavone. Drug-cyclodextrin solid systems were prepared by freeze-drying. Phase solubility study was used to evaluate the complexation in solution, of two cyclodextrins, i.e., betaCD and HPbetaCD. The stoichiometry and stability constants of QURC-betaCD (1:1 and 402M(-1)) and QURC-HPbetaCD (1:1 and 532M(-1)) complexes were calculated by phase solubility method. The formation of inclusion complexes with betaCD and HPbetaCD in the solid-state were confirmed by infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy (SEM). 10.1016/S0731-7085(03)00529-6
    Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-beta-cyclodextrin. Liu Jun,Qiu Liyan,Gao Jianqing,Jin Yi International journal of pharmaceutics The interaction of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and a poorly water-soluble flavonoid, baicalein (Ba), chemically 5,6,7-trihydroxy flavone in solution and solid-state was studied. Ba/HP-beta-CD solid systems were prepared by freeze-drying method. The formation of Ba/HP-beta-CD complex in aqueous solution was demonstrated by UV spectroscopy, while Ba/HP-beta-CD co-lyophilized product was characterized by differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Through complexation with HP-beta-CD, the solubility of Ba in neutral aqueous solution was improved significantly. The phase-solubility profile was AP-type, indicating the formation of higher-order complexes or complex aggregates. Ba/HP-beta-CD solid powders were amorphous and show a significantly improved dissolution rate in comparison with free Ba. Comparison of the pharmacokinetics between Ba/HP-beta-CD co-lyophilized product and free Ba was also performed in rats. The concentration of Ba and its mainly conjugated metabolite, 7-O-glucuronide of baicalein (BG) in rat plasma was determined by HPLC method. The in vivo results show that Ba/HP-beta-CD co-lyophilized product exhibits the similar pharmacokinetics as that of free Ba after intravenous administration. Ba/HP-beta-CD co-lyophilized product displays earlier tmax and higher Cmax of BG than free Ba after oral dosing. By comparing the AUC0-infinity of BG between oral dosing, the relative bioavailability of Ba/HP-beta-CD co-lyophilized product to free Ba was 165.0%, which highlighted the evidence of significantly improved bioavailability of formulation of Ba with HP-beta-CD. 10.1016/j.ijpharm.2006.01.011
    Preparation, characterization, and preliminary antibrowning evaluations of norartocarpetin microemulsions. Zheng Zong-Ping,Dong Xue,Yuan Kun,Lan Shan,Zhu Qin,Wang Mingfu,Chen Jie Journal of agricultural and food chemistry Norartocarpetin is a flavone widely distributed in Moraceae plants with strong tyrosinase inhibitory activity. However, its poor solubility in aqueous systems and in food grade solvents (oils) limits its extensive applications. The aim of this study was to improve the solubility of norartocarpetin by developing an oil-in-water (o/w) microemulsion with food grade components. A microemulsion was developed and characterized, and its chemical and physical stabilities were also evaluated within 8 weeks. Using the construction of pseudoternary phase diagrams, the optimized formulation of 2% w/w of ethyl oleate, 12% w/w of Tween 80, 6% w/w of polyethylene glycol 400, and 80% w/w of water was obtained, with a maximum solubility of norartocarpetin up to 1.73 ± 0.21 mg/mL, at least a 1000-fold increase in solubility. The microemulsion base and norartocarpetin-loaded microemulsion were demonstrated to be stable after accelerated and long-term conditions (8 weeks). The norartocarpetin microemulsion still showed strong tyrosinase inhibitory activity and antibrowning effect on fresh-cut apple slices. These combined results indicated that norartocarpetin microemulsion may be suitable as an antibrowning agent for fresh-cut fruits. 10.1021/jf5048805
    Enhancement of the water solubility of flavone glycosides by disruption of molecular planarity of the aglycone moiety. Lewin Guy,Maciuk Alexandre,Moncomble Aurélien,Cornard Jean-Paul Journal of natural products Enhancement of the water solubility by disruption of molecular planarity has recently been reviewed as a feasible approach in small-molecule drug discovery programs. We applied this strategy to some natural flavone glycosides, especially diosmin, a highly insoluble citroflavonoid prescribed as an oral phlebotropic drug. Disruption of planarity at the aglycone moiety by 3-bromination or chlorination afforded 3-bromo- and 3-chlorodiosmin, displaying a dramatic solubility increase compared with the parent compound. 10.1021/np300460a
    Structural modification aimed for improving solubility of lead compounds in early phase drug discovery. Das Bhanuranjan,Baidya Anurag T K,Mathew Alen T,Yadav Ashok Kumar,Kumar Rajnish Bioorganic & medicinal chemistry Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery. Solubility improvement of poorly soluble lead compounds without losing potency is a challenging task for the medicinal chemist in a drug discovery setup. Solubility is an important factor not only to dissipate or liquefy a substance but also to attain an optimal concentration of drug in systemic circulation required for the desired therapeutic effect. It has been estimated that more than forty percent of newly developed molecules are practically insoluble in water. Molecules with poor solubility not only cause difficulty for in vitro and in vivo assays but also add significant burdens to drug development in the form of longer time taken and increased cost to optimize the solubility. To tackle this problem, different techniques are being used such as physical, chemical, and miscellaneous methods to enhance solubility. Among them, the medicinal chemistry approach focussed on structural modification is a versatile and unique approach in way that it can also improve other pharmacokinetic/physicochemical parameters simultaneously. In this review, we have begun with brief introduction of solubility and its role followed by recent successful examples of different structural modification tactics reported in the literature including synthesis of prodrugs, hydrophilic and ionizable group insertion, addition & removal of hydrogen bonding, bioisosterism, disruption of molecular symmetry and planarity. Moreover, we have included a section on the obstacles in the solubility optimization and also summarised different in silico tools with potential application in solubility prediction. Overall, this review encompasses various successfully used solubility optimization examples using structure modification. 10.1016/j.bmc.2022.116614
    Overview of nanoparticulate strategies for solubility enhancement of poorly soluble drugs. Khan Kifayat Ullah,Minhas Muhammad Usman,Badshah Syed Faisal,Suhail Muhammad,Ahmad Aousaf,Ijaz Shakeel Life sciences Poor aqueous solubility and poor bioavailability are major issues with many pharmaceutical industries. By some estimation, 70-90% drug candidates in development stage while up-to 40% of the marketed products are poorly soluble which leads to low bioavailability, reduced therapeutic effects and dosage escalation. That's why solubility is an important factor to consider during design and manufacturing of the pharmaceutical products. To-date, various strategies have been explored to tackle the issue of poor solubility. This review article focuses the updated overview of commonly used macro and nano drug delivery systems and techniques such as micronization, solid dispersion (SD), supercritical fluid (SCF), hydrotropy, co-solvency, micellar solubilization, cryogenic technique, inclusion complex formation-based techniques, nanosuspension, solid lipid nanoparticles, and nanogels/nanomatrices explored for solubility enhancement of poorly soluble drugs. Among various techniques, nanomatrices were found a promising and impeccable strategy for solubility enhancement of poorly soluble drugs. This article also describes the mechanism of action of each technique used in solubilization enhancement. 10.1016/j.lfs.2022.120301
    Choline-Amino Acid-Derived Bio-ionic Liquids for Solubility Enhancement of Zafirlukast. AAPS PharmSciTech This study investigated the application of bio-ionic liquids (ILs) prepared from choline as cation and amino acid as anion for solubility enhancement of poorly water-soluble drug, Zafirlukast (ZFL). Herein, the solubility of ZFL in water and mixtures of water and ILs was assessed using UV spectroscopy at two temperature points 25°C and 37°C with increasing concentrations of IL. ZFL solubility was found to improve linearly with increasing concentration of [Ch][Pro] in water, representing 35- to 37-fold improvement in ZFL solubility at maximum concentration of [Ch][Pro] (1% w/v) compared to when only pure water was present. Also, the effect of IL on ZFL solubility was analyzed using NMR, DSC, and TGA. These results clearly suggest that ZFL solubility was increased by forming hydrogen bonds with selected [Ch][Pro] IL. Toxicity study of ILs was tested against gram-positive and gram-negative bacteria. Since IL solvent was found to increase the solubility of ZFL, this may serve as "functional excipient solvent" for solubility enhancement in its commercialized formulations. 10.1208/s12249-022-02296-8
    Improved water solubility, chemical stability, antioxidant and anticancer activity of resveratrol via nanoencapsulation with pea protein nanofibrils. Yi Jiang,He Qingyu,Peng Gaofei,Fan Yuting Food chemistry Fabricated pea protein isolate (PPI) nanofibrils were used as nanocarriers to encapsulate, stabilize and deliver resveratrol (RES). PPI nanofibrils possessed a dramatically higher surface hydrophobicity than PPI (native), and PPI nanofibrils exhibited nanoscale widths of 10 nm and average lengths of 1.0 μm. Fluorescence analyses demonstrated PPI nanofibrils had high binding constant with RES. Compared with RES (free), the aqueous solubility of RES was improved by approximately 1000-fold with PPI nanofibrils complex. DPPH and ABTS radical scavenging activity assays showed that the antioxidant capacity of RES was pronouncedly enhanced through the nanocomplexation with PPI nanofibrils. RES-PPI nanofibrils complexes exhibited higher antiproliferative activities than RES (free), with the cell viabilities of 52.6% and 38.5% for RES (free) and RES-PPI nanofibrils complex at 20 μg/mL. This study demonstrates that PPI nanofibrils can be utilized as novel nanocarriers for improvements of the water solubility, chemical stability and in vitro biological activities of hydrophobic nutraceuticals. 10.1016/j.foodchem.2021.131942
    Enhanced Drug Delivery by Dissolution of Amorphous Drug Encapsulated in a Water Unstable Metal-Organic Framework (MOF). Suresh Kuthuru,Matzger Adam J Angewandte Chemie (International ed. in English) Encapsulating a drug molecule into a water-reactive metal-organic framework (MOF) leads to amorphous drug confined within the nanoscale pores. Rapid release of drug occurs upon hydrolytic decomposition of MOF in dissolution media. Application to improve dissolution and solubility for the hydrophobic small drug molecules curcumin, sulindac, and triamterene is demonstrated. The drug@MOF composites exhibit significantly enhanced dissolution and achieves high supersaturation in simulated gastric and/or phosphate buffer saline media. This combination strategy where MOF inhibits crystallization of the amorphous phase and then releases drug upon MOF irreversible structural collapse represents a novel and generalizable approach for drug delivery of poorly soluble compounds while overcoming the traditional weakness of amorphous drug delivery: physical instability of the amorphous form. 10.1002/anie.201907652
    The solubility-permeability interplay and oral drug formulation design: Two heads are better than one. Dahan Arik,Beig Avital,Lindley David,Miller Jonathan M Advanced drug delivery reviews Poor aqueous solubility is a major challenge in today's biopharmaceutics. While solubility-enabling formulations can significantly increase the apparent solubility of the drug, the concomitant effect on the drug's apparent permeability has been largely overlooked. The mathematical equation to describe the membrane permeability of a drug comprises the membrane/aqueous partition coefficient, which in turn is dependent on the drug's apparent solubility in the GI milieu, suggesting that the solubility and the permeability are closely related, exhibit a certain interplay between them, and treating the one irrespectively of the other may be insufficient. In this article, an overview of this solubility-permeability interplay is provided, and the available data is analyzed in the context of the effort to maximize the overall drug exposure. Overall, depending on the type of solubility-permeability interplay, the permeability may decrease, remain unchanged, and even increase, in a way that may critically affect the formulation capability to improve the overall absorption. Therefore, an intelligent design of solubility-enabling formulation needs to consider both the solubility afforded by the formulation and the permeability in the new luminal environment resulting from the formulation. 10.1016/j.addr.2016.04.018
    Sketching neoteric solvents for boosting drugs bioavailability. Álvarez María S,Zhang Yanfei Journal of controlled release : official journal of the Controlled Release Society Emerging neoteric solvents are being the subject of growing attention due to their lower cost and environmental impact, so they are being applied in a broad spectrum of industries. Among them, the pharmaceutical sector is demanding new environmentally friendly and non-toxic solvents able to enhance drugs solubility and stability. The introduction of ionic liquids turned out to be a breakthrough in the field of Green Chemistry opening up new separation and catalysis opportunities. In this sense, the options represented by Deep Eutectic Solvents make up an attractive alternative due to the low cost of their raw material, simple synthesis, and eco-friendly character. In line with these findings, Therapeutic Deep Eutectic Solvents and Natural Deep Eutectic Solvents are new and promising alternatives to improve the bioavailability of drugs in pharmaceutical formulations. This leading article is focused on providing a general picture of the advantages and drawbacks of these new solvents as well as the main research lines and perspectives to achieve efficient drugs delivery systems. 10.1016/j.jconrel.2019.09.008
    Delivery of paclitaxel using PEGylated graphene oxide as a nanocarrier. Xu Zhiyuan,Zhu Shaojia,Wang Mingwei,Li Yongjun,Shi Ping,Huang Xiaoyu ACS applied materials & interfaces Paclitaxel (PTX) is an extensively used potent chemotherapy drug; however, low water solubility, poor bioavailability, and emergence of drug resistance in patients limited its biological application. In this report, we proposed a new drug delivery system for cancer therapy based on graphene oxide (GO), a novel 2D nanomaterial obtained from the oxidation of natural graphite, to improve the utilization rate of PTX. PTX was first connected to biocompatible 6-armed poly(ethylene glycol), followed by covalent introduction into the surface of GO sheets via a facile amidation process under mild conditions, affording the drug delivery system, GO-PEG-PTX (size 50-200 nm). GO-PEG nanosized carrier could quickly enter into human lung cancer A549 and human breast cancer MCF-7 cells verified by inverted fluorescence microscope using fluorescein isothiocyanate as probe. This nanocarrier was nontoxic to A549 and MCF-7 cells without linking with PTX. Nevertheless, GO-PEG-PTX showed remarkably high cytotoxicity to A549 and MCF-7 cells in a broad range of concentration of PTX and time compared to free PTX. This kind of nanoscale drug delivery system based on PEGylated GO may find widespread application in biomedicine. 10.1021/am507798d
    Simvastatin prodrug micelles target fracture and improve healing. Jia Zhenshan,Zhang Yijia,Chen Yen Hsun,Dusad Anand,Yuan Hongjiang,Ren Ke,Li Fei,Fehringer Edward V,Purdue P Edward,Goldring Steven R,Daluiski Aaron,Wang Dong Journal of controlled release : official journal of the Controlled Release Society Simvastatin (SIM), a widely used anti-lipidemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug's hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles' therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing. 10.1016/j.jconrel.2014.12.028
    Nanosizing techniques for improving bioavailability of drugs. Al-Kassas Raida,Bansal Mahima,Shaw John Journal of controlled release : official journal of the Controlled Release Society The poor solubility of significant number of Active Pharmaceutical Ingredients (APIs) has become a major challenge in the drug development process. Drugs with poor solubility are difficult to formulate by conventional methods and often show poor bioavailability. In the last decade, attention has been focused on developing nanocrystals for poorly water soluble drugs using nanosizing techniques. Nanosizing is a pharmaceutical process that changes the size of a drug to the sub-micron range in an attempt to increase its surface area and consequently its dissolution rate and bioavailability. The effectiveness of nanocrystal drugs is evidenced by the fact that six FDA approved nanocrystal drugs are already on the market. The bioavailabilities of these preparations have been significantly improved compared to their conventional dosage forms. There are two main approaches for preparation of drug nanocrystals; these are the top-down and bottom-up techniques. Top-down techniques have been successfully used in both lab scale and commercial scale manufacture. Bottom-up approaches have not yet been used at a commercial level, however, these techniques have been found to produce narrow sized distribution nanocrystals using simple methods. Bottom-up techniques have been also used in combination with top-down processes to produce drug nanoparticles. The main aim of this review article is to discuss the various methods for nanosizing drugs to improve their bioavailabilities. 10.1016/j.jconrel.2017.06.003
    Performance of Doxorubicin-Conjugated Gold Nanoparticles: Regulation of Drug Location. Cui Teng,Liang Juan-Juan,Chen Huan,Geng Dong-Dong,Jiao Lei,Yang Jian-Yong,Qian Hai,Zhang Can,Ding Ya ACS applied materials & interfaces Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHN═Dox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 μg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents. 10.1021/acsami.6b16669
    Nano-amorphous spray dried powder to improve oral bioavailability of itraconazole. Kumar Sumit,Shen Jie,Burgess Diane J Journal of controlled release : official journal of the Controlled Release Society The objective of this study was to formulate nano-amorphous spray-dried powders of itraconazole to enhance its oral bioavailability. A combination approach of solvent-antisolvent precipitation followed by spray drying was used. DoE studies were utilized to understand the critical processing parameters: antisolvent-to-solvent ratio, drug concentration and stabilizer concentration. Particle size was the critical quality attribute. Spray drying of the nano-precipitated formulation was performed with several auxiliary excipients to obtain nano-sized amorphous powder formulations. PLM, DSC and PXRD were utilized to characterize the spray-dried powders. In vitro dissolution and in vivo bioavailability studies of the nano-amorphous powders were performed. The particle size of the nano-formulations was dependent on the drug concentration. The smallest size precipitates were obtained with low drug concentration. All high molecular weight auxiliary excipients and mannitol containing formulations were unstable and crystallized during spray drying. Formulations containing disaccharides were amorphous and non-aggregating. In vitro dissolution testing and in vivo studies showed the superior performance of nano-amorphous formulations compared to melt-quench amorphous and crystalline itraconazole formulations. This study shows superior oral bioavailability of nano-amorphous powders compared to macro-amorphous powders. The nano-amorphous formulation showed similar bioavailability to the nano-crystalline formulation but with a faster absorption profile. 10.1016/j.jconrel.2014.06.059
    Enhanced topical penetration, system exposure and anti-psoriasis activity of two particle-sized, curcumin-loaded PLGA nanoparticles in hydrogel. Sun Lin,Liu Zeyu,Wang Lun,Cun Dongmei,Tong Henry H Y,Yan Ru,Chen Xin,Wang Ruibing,Zheng Ying Journal of controlled release : official journal of the Controlled Release Society Psoriasis is an immune-mediated skin disorder, which is triggered by the aberrant activation of dendritic cells in skin. This activation is followed by the complex interaction between the immune cells in the skin and keratinocyte in the epidermis. To improve the conditions of poor aqueous solubility and chemical stability, overcome skin barriers, and enhance in vivo anti-psoriatic activity, curcumin (Cur) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were fabricated and administered by topical route to treat imiquimod (IMQ)-induced psoriasis-like mouse model. Spherical Cur-NPs with the mean particle sizes of 50nm and 150nm, respectively, were fabricated using a multi-inlet vortex mixer system, with both exhibiting significantly stronger anti-proliferation effect than Cur solution on HaCaT cells in vitro. Psoriatic skin was utilized in the in vitro skin penetration studies, and the results demonstrated that more drugs penetrated through or accumulated in the skin when administered as the Cur-NPs-loaded hydrogel compared to the drug suspension loaded hydrogel. To compare the nanosizing effect of these Cur-NPs, the mice with IMQ-induced psoriasis-like skin disease were treated with blank gel, Cur gel, 50nm sized NPs gel, 150nm sized NPs gel or tracrolimus cream (positive control), respectively. The results indicated that Cur-NPs hydrogel has a superior performance to Cur hydrogel on the IMQ-induced psoriasis-like mouse model in terms of morphological evaluation, biomarkers at mRNA, and protein levels. In conclusion, encapsulation of Cur into PLGA NPs, particularly for NPs of 50nm, could facilitate lipophilic Cur's dispersion, sustained-release, accumulation, and penetration across the skin and into the blood circulation, which significantly improves anti-psoriasis activity in mice. 10.1016/j.jconrel.2017.03.385
    Strategies for the Optimization of Natural Leads to Anticancer Drugs or Drug Candidates. Xiao Zhiyan,Morris-Natschke Susan L,Lee Kuo-Hsiung Medicinal research reviews Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship directed optimization and pharmacophore-oriented molecular design based on the natural templates. Both fundamental medicinal chemistry principles (e.g., bioisosterism) and state-of-the-art computer-aided drug design techniques (e.g., structure-based design) can be applied to facilitate optimization efforts. In this review, the strategies to optimize natural leads to anticancer drugs or drug candidates are illustrated with examples and described according to their purposes. Furthermore, successful case studies on lead optimization of bioactive compounds performed in the Natural Products Research Laboratories at UNC are highlighted. 10.1002/med.21377
    Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation. Sayed Elshaimaa,Karavasili Christina,Ruparelia Ketan,Haj-Ahmad Rita,Charalambopoulou Georgia,Steriotis Theodore,Giasafaki Dimitra,Cox Paul,Singh Neenu,Giassafaki Lefki-Pavlina N,Mpenekou Aggeliki,Markopoulou Catherine K,Vizirianakis Ioannis S,Chang Ming-Wei,Fatouros Dimitrios G,Ahmad Zeeshan Journal of controlled release : official journal of the Controlled Release Society Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials. 10.1016/j.jconrel.2018.03.031
    Pharmaceutical strategies of improving oral systemic bioavailability of curcumin for clinical application. Ma Ziwei,Wang Na,He Haibing,Tang Xing Journal of controlled release : official journal of the Controlled Release Society Curcumin (Cur), a natural compound from Curcuma longa Linn, has various of pharmacological activities such as anti-cancer, anti-inflammatory, anti-oxidant, anti-Alzheimer, anti-microbial and more. Curcumin also has nephroprotective, hepatoprotective, neuroprotective, antirheumatic and cardioprotective effects. However, its low aqueous solubility inhibits the oral bioavailability of curcumin. As well, curcumin can be metabolized rapidly by intestinal tract which can also result in low oral bioavailability. In fact, the bioavailability of curcumin is low even through intraveneous administration routes. Various of pharmaceutical strategies for oral administration including solid dispersions, nano/microparticles, polymeric micelles, nanosuspensions, lipid-based nanocarriers, cyclodextrins, conjugates, polymorphs have been developed in order to improve the oral bioavailability of curcumin. These pharmaceutical strategies can increase the solubility of curcumin, improve the intestinal stability of curcumin, change the absorption route of curcumin and allow for coadministration with other adjuvants. Here we discuss efficacy studies in vitro and in vivo of curcumin nanoformulations, as well as human clinical trials. 10.1016/j.jconrel.2019.10.053
    Basic principles of drug delivery systems - the case of paclitaxel. Ezrahi S,Aserin A,Garti N Advances in colloid and interface science Cancer is the second cause of death worldwide, exceeded only by cardiovascular diseases. The prevalent treatment currently used against metastatic cancer is chemotherapy. Among the most studied drugs that inhibit neoplastic cells from acquiring unlimited replicative ability (a hallmark of cancer) are the taxanes. They operate via a unique molecular mechanism affecting mitosis. In this review, we show this mechanism for one of them, paclitaxel, and for other (non-taxanes) anti-mitotic drugs. However, the use of paclitaxel is seriously limited (its bioavailability is <10%) due to several long-standing challenges: its poor water solubility (0.3 μg/mL), its being a substrate for the efflux multidrug transporter P-gp, and, in the case of oral delivery, its first-pass metabolism by certain enzymes. Adequate delivery methods are therefore required to enhance the anti-tumor activity of paclitaxel. Thus, we have also reviewed drug delivery strategies in light of the various physical, chemical, and enzymatic obstacles facing the (especially oral) delivery of drugs in general and paclitaxel in particular. Among the powerful and versatile platforms that have been developed and achieved unprecedented opportunities as drug carriers, microemulsions might have great potential for this aim. This is due to properties such as thermodynamic stability (leading to long shelf-life), increased drug solubilization, and ease of preparation and administration. In this review, we define microemulsions and nanoemulsions, analyze their pertinent properties, and review the results of several drug delivery carriers based on these systems. 10.1016/j.cis.2018.11.004