Displaying publications 1 - 20 of 27 in total

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  1. Enhanced nanocurcumin toxicity against (PC3) tumor and microbial by using magnetic field in vitro
    Aldahoun MA, Jaafar MS, Al-Akhras MH, Bououdina M
    Artif Cells Nanomed Biotechnol, 2017 Jun;45(4):843-853.
    PMID: 27137748 DOI: 10.1080/21691401.2016.1178137
    Curcumin is more soluble in ethanol, dimethylsulfoxide, methanol and acetone than in water. In this study, nanocurcumin combined with 8 mT AC static magnetic field was used to enhance cellular uptake, bioavailability, and ultimate efficiency of curcumin against prostate cancer cell line (PC3), four bacteria strains (two Gram positive: Micrococcus luteus ATCC 9341, Staphylococcus aureus ATCC 29213 and two Gram negative: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853), mammalian cell line (HEK) and human erythrocytes (RBC). The efficiency (E%) between IC50 of nanocurcumin combined with magnetic field (NANOCUR-MF) and control against PC3 was 35.93%, which is three times higher compared to curcumin combined with magnetic field (CUR-MF); i.e., 10.77%. However, their E% against HEK was not significant; 1.4% for NANOCUR-MF and 1.95% for CUR-MF. Moreover, depending in minimum bacterial concentration (MBC), the use of MF leads to a reduction of MBCs for all tested bacteria compared with control. The obtained results established the applicability of (MF) in enhancing cellular uptake for PC3 and tested bacteria strains by increasing the penetration of drug (nanocurcumin and parent curcumin) into cell with fixing mild cytotoxic profile for HEK and RBC.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  2. Mucoadhesive Chitosan-Pectinate Nanoparticles for the Delivery of Curcumin to the Colon
    Alkhader E, Billa N, Roberts CJ
    AAPS PharmSciTech, 2017 May;18(4):1009-1018.
    PMID: 27582072 DOI: 10.1208/s12249-016-0623-y
    In the present study, we report the properties of a mucoadhesive chitosan-pectinate nanoparticulate formulation able to retain its integrity in the milieu of the upper gastrointestinal tract and subsequently, mucoadhere and release curcumin in colon conditions. Using this system, we aimed to deliver curcumin to the colon for the possible management of colorectal cancer. The delivery system comprised of a chitosan-pectinate composite nanopolymeric with a z-average of 206.0 nm (±6.6 nm) and zeta potential of +32.8 mV (±0.5 mV) and encapsulation efficiency of 64%. The nanoparticles mucoadhesiveness was higher at alkaline pH compared to acidic pH. Furthermore, more than 80% release of curcumin was achieved in pectinase-enriched medium (pH 6.4) as opposed to negligible release in acidic and enzyme-restricted media at pH 6.8. SEM images of the nanoparticles after exposure to the various media indicate a retained matrix in acid media as opposed to a distorted/fragmented matrix in pectinase-enriched medium. The data strongly indicates that the system has the potential to be applied as a colon-targeted mucoadhesive curcumin delivery system for the possible treatment of colon cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  3. Pharmacokinetic and anti-colon cancer properties of curcumin-containing chitosan-pectinate composite nanoparticles
    Alkhader E, Roberts CJ, Rosli R, Yuen KH, Seow EK, Lee YZ, et al.
    J Biomater Sci Polym Ed, 2018 12;29(18):2281-2298.
    PMID: 30376409 DOI: 10.1080/09205063.2018.1541500
    Curcumin, the active ingredient of the rhizome curcuma longa has been extensively studied as an anticancer agent for various types of tumours. However, its efficacy as an anticancer agent is restricted due to poor absorption from the gastrointestinal tract, rapid metabolism and degradation in acidic medium. In the present study, we encapsulated curcumin in chitosan-pectinate nanoparticulate system (CUR-CS-PEC-NPs) for deployment of curcumin to the colon, whereby curcumin is protected against degradative effects in the upper digestive tract, and hence, maintaining its anticancer properties until colon arrival. The CUR-CS-PEC-NPs was taken up by HT-29 colorectal cancer cells which ultimately resulted in a significant reduction in cancer cell propagation. The anti-proliferative effect of the encapsulated curcumin was similar to that of free curcumin at equivalent doses which confirms that the encapsulation process did not impede the anticancer activity of curcumin. The oral bioavailability (Cmax, and AUC) of curcumin in CUR-CS-PEC-NPs was enhanced significantly by 4-folds after 6 hours of treatment compared to free curcumin. Furthermore, the clearance of curcumin from the CUR-CS-PEC-NPs was lower compared to free curcumin. These findings point to the potential application of the CUR-CS-PEC-NPs in the oral delivery of curcumin in the treatment of colon cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  4. Fulltext Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design
    Asmawi AA, Salim N, Abdulmalek E, Abdul Rahman MB
    Int J Mol Sci, 2020 Jun 19;21(12).
    PMID: 32575390 DOI: 10.3390/ijms21124357
    The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  5. Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified cytotoxicity and bioavailability
    Badran MM, Alomrani AH, Harisa GI, Ashour AE, Kumar A, Yassin AE
    Biomed Pharmacother, 2018 Oct;106:1461-1468.
    PMID: 30119220 DOI: 10.1016/j.biopha.2018.07.102
    In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  6. Fulltext Preparation and controlled-release studies of a protocatechuic acid-magnesium/aluminum-layered double hydroxide nanocomposite
    Barahuie F, Hussein MZ, Hussein-Al-Ali SH, Arulselvan P, Fakurazi S, Zainal Z
    Int J Nanomedicine, 2013;8:1975-87.
    PMID: 23737666 DOI: 10.2147/IJN.S42718
    In the study reported here, magnesium/aluminum (Mg/Al)-layered double hydroxide (LDH) was intercalated with an anticancer drug, protocatechuic acid, using ion-exchange and direct coprecipitation methods, with the resultant products labeled according to the method used to produce them: "PANE" (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the ion-exchange method) and "PAND" (ie, protocatechuic acid-Mg/Al nanocomposite synthesized using the direct method), respectively. Powder X-ray diffraction and Fourier transform infrared spectroscopy confirmed the intercalation of protocatechuic acid into the inter-galleries of Mg/Al-LDH. The protocatechuic acid between the interlayers of PANE and PAND was found to be a monolayer, with an angle from the z-axis of 8° for PANE and 15° for PAND. Thermogravimetric and differential thermogravimetric analysis results revealed that the thermal stability of protocatechuic acid was markedly enhanced upon intercalation. The loading of protocatechuic acid in PANE and PAND was estimated to be about 24.5% and 27.5% (w/w), respectively. The in vitro release study of protocatechuic acid from PANE and PAND in phosphate-buffered saline at pH 7.4, 5.3, and 4.8 revealed that the nanocomposites had a sustained release property. After 72 hours incubation of PANE and PAND with MCF-7 human breast cancer and HeLa human cervical cancer cell lines, it was found that the nanocomposites had suppressed the growth of these cancer cells, with a half maximal inhibitory concentration of 35.6 μg/mL for PANE and 36.0 μg/mL for PAND for MCF-7 cells, and 19.8 μg/mL for PANE and 30.3 μg/mL for PAND for HeLa cells. No half maximal inhibitory concentration for either nanocomposite was found for 3T3 cells.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  7. Fulltext Anticancer nanodelivery system with controlled release property based on protocatechuate-zinc layered hydroxide nanohybrid
    Barahuie F, Hussein MZ, Abd Gani S, Fakurazi S, Zainal Z
    Int J Nanomedicine, 2014;9:3137-49.
    PMID: 25061291 DOI: 10.2147/IJN.S59541
    BACKGROUND: We characterize a novel nanocomposite that acts as an efficient anticancer agent.

    METHODS: This nanocomposite consists of zinc layered hydroxide intercalated with protocatechuate (an anionic form of protocatechuic acid), that has been synthesized using a direct method with zinc oxide and protocatechuic acid as precursors.

    RESULTS: The resulting protocatechuic acid nanocomposite (PAN) showed a basal spacing of 12.7 Å, indicating that protocatechuate was intercalated in a monolayer arrangement, with an angle of 54° from the Z-axis between the interlayers of the zinc layered hydroxide, and an estimated drug loading of about 35.7%. PAN exhibited the properties of a mesoporous type material, with greatly enhanced thermal stability of protocatechuate as compared to its free counterpart. The presence of protocatechuate in the interlayers of the zinc layered hydroxide was further supported by Fourier transform infrared spectroscopy. Protocatechuate was released from PAN in a slow and sustained manner. This mechanism of release was well represented by a pseudo-second order kinetics model. PAN has shown increased cytotoxicity compared to the free form of protocatechuic acid in all cancer cell lines tested. Tumor growth suppression was extensive, particularly in HepG2 and HT29 cell lines.

    CONCLUSION: PAN is suitable for use as a controlled release formulation, and our in vitro evidence indicates that PAN is an effective anticancer agent. PAN may have potential as a chemotherapeutic drug for human cancer.

    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  8. Fulltext Wheat Germ Agglutinin-Conjugated Disulfide Cross-Linked Alginate Nanoparticles as a Docetaxel Carrier for Colon Cancer Therapy
    Chiu HI, Lim V
    Int J Nanomedicine, 2021;16:2995-3020.
    PMID: 33911862 DOI: 10.2147/IJN.S302238
    PURPOSE: In chemotherapy, oral administration of drug is limited due to lack of drug specificity for localized colon cancer cells. The inability of drugs to differentiate cancer cells from normal cells induces side effects. Colonic targeting with polymeric nanoparticulate drug delivery offers high potential strategies for delivering hydrophobic drugs and fewer side effects to the target site. Disulfide cross-linked polymers have recently acquired high significance due to their potential to degrade in reducing colon conditions while resisting the upper gastrointestinal tract's hostile environment. The goal of this project is, therefore, to develop pH-sensitive and redox-responsive fluorescein-labeled wheat germ agglutinin (fWGA)-mounted disulfide cross-linked alginate nanoparticles (fDTP2) directly targeting docetaxel (DTX) in colon cancer cells.

    METHODS: fDTP2 was prepared by mounting fWGA on DTX-loaded nanoparticles (DTP2) using the two-step carbodiimide method. Morphology of fDTP2 was examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) study was carried out to determine the mean diameter, polydispersity index (PDI) and zeta potential of fDTP2. Cellular uptake efficiency was examined using fluorescence microplate reader. Biocompatibility and active internalization of fDTP2 were conducted on HT-29.

    RESULTS: fDTP2 was found to exhibit a DTX loading efficiency of 19.3%. SEM and TEM tests revealed spherical nanoparticles. The in vitro DTX release test showed a cumulative release of 54.7%. From the DLS study, fDTP2 reported a 277.7 nm mean diameter with PDI below 0.35 and -1.0 mV zeta potential. HT-29 which was fDTP2-treated demonstrated lower viability than L929 with a half maximal inhibitory concentration (IC50) of 34.7 µg/mL. HT-29 (33.4%) internalized fDTP2 efficiently at 2 h incubation. The study on HT-29 active internalization of nanoparticles through fluorescence and confocal imaging indicated such.

    CONCLUSION: In short, fDTP2 demonstrated promise as a colonic drug delivery DTX transporter.

    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  9. Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles
    Chuah LH, Roberts CJ, Billa N, Abdullah S, Rosli R
    Colloids Surf B Biointerfaces, 2014 Apr 1;116:228-36.
    PMID: 24486834 DOI: 10.1016/j.colsurfb.2014.01.007
    Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  10. Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line
    Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Kura AU, Zakaria ZAB
    In Vitro Cell Dev Biol Anim, 2017 Dec;53(10):896-907.
    PMID: 28916966 DOI: 10.1007/s11626-017-0197-3
    Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p 
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  11. Lycopene loaded whey protein isolate nanoparticles: An innovative endeavor for enhanced bioavailability of lycopene and anti-cancer activity
    Jain A, Sharma G, Ghoshal G, Kesharwani P, Singh B, Shivhare US, et al.
    Int J Pharm, 2018 Jul 30;546(1-2):97-105.
    PMID: 29715533 DOI: 10.1016/j.ijpharm.2018.04.061
    The work entails a novel strategy of formulating the lycopene loaded whey protein isolate nanoparticles (LYC-WPI-NPs) solely using the rational blend of biomacromolecule without using equipment-intensive techniques. The LYC-WPI-NPs were fabricated as a substantial drug delivery platform, with maximum entrapment, spatial and controlled release manners, exceptional plasma concentration, and perspective for discrepancy delivery of therapeutics. Prepared nano-formulations were measured in ultra-fine size (100-350 nm) with sphere-shaped. The percent lycopene entrapment of prepared LYC-WPI-NPs was estimated in the range to 50 and 65%. In vitro percent cumulative release study demonstrated deaden and extended release i.e. approximately 75% following 16th h. The in vitro percent cell survival (cytotoxicity study) of prepared nanoparticles was evaluated against MCF-7 breast cancer cells by MTT based colorimetric assay. Sub-cellular localization of lycopene when delivered by LYC-WPI-NPs was assessed by HPLC (high performance liquid chromatography). The WPI-NPs enhance the oral bioavailability of lycopene by controlling its release from nano-formulation and facilitating its absorption through lymphatic pathways. Prophylactic anticancer efficacy of LYC-WPI-NPs was evaluated thereafter on experimentally induced breast cancer animal model. Conclusively, it may quite reasonable that lycopene loaded protein nanoparticles are competent to improve the biopharmaceutical attributes of lycopene and demonstrated prophylactic anticancer activity, decrease tumor proliferation and increase the survival rate of treated animals, thus signifying their feasible usefulness in cancer therapeutic and intervention.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  12. Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar systems
    Khurana RK, Beg S, Burrow AJ, Vashishta RK, Katare OP, Kaur S, et al.
    Eur J Pharm Biopharm, 2017 Dec;121:42-60.
    PMID: 28887099 DOI: 10.1016/j.ejpb.2017.09.001
    The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul <5min, Dnm <100nm, Rel15min >85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  13. The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery
    Ma Y, Fuchs AV, Boase NR, Rolfe BE, Coombes AG, Thurecht KJ
    Eur J Pharm Biopharm, 2015 Aug;94:393-403.
    PMID: 26117186 DOI: 10.1016/j.ejpb.2015.06.014
    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  14. Structure of the d(CGCGAATTCGCG)2 complex of the minor groove binding alkylating agent alkamin studied by mass spectrometry
    Majid AM, Smythe G, Denny WA, Wakelin LP
    Mol. Pharmacol., 2007 Apr;71(4):1165-78.
    PMID: 17251328
    Nitrogen mustard alkylating agents are important cancer drugs. Much interest has been focused on redirecting their covalent adducts from the N7 atoms of guanine in the major groove of DNA to the N3 atoms of adenine in the minor groove by attaching mustard groups to AT-selective minor groove binding ligands. Here we describe the use of electrospray ionization and matrix-assisted laser desorption ionization/time-of-flight mass spectrometry to study the structure of the DNA complexes of two minor groove binding polybenzamide mustards, alkamin and alkamini; the former is a bis-half-mustard in which reactive groups are disposed at each end of the ligand, and the latter is its monofunctional analog. Alkamin is potently cytotoxic and active in experimental mouse tumor models, whereas alkamini is not. We have studied their interaction with the DNA dodecamer d(CGCGAATTCGCG)(2), designated A2T2, and we provide a detailed analysis of the observed DNA-ligand adduct ions and their fragmentation products. We find that alkamini alkylates A2T2 at guanine G4 and adenines A5 and A6 in a manner consistent with covalent attack on purine N3 atoms from the minor groove of the AT tract. Alkamin also forms monofunctional adducts at G4 and both adenines in which the second mustard arm is hydrolyzed but, in addition, forms a variety of interstrand cross-links between adenines A5/A6 and A5'/A6', an interstrand cross-link between G4 and A6', and an intrastrand cross-link between G4 and A6. We conclude that the marked cytotoxicity of alkamin and its experimental antitumor activity could be the consequence of its ability to cross-link cellular DNA at AT tract sequences.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  15. Biological Properties of Tocotrienols: Evidence in Human Studies
    Meganathan P, Fu JY
    Int J Mol Sci, 2016 Oct 26;17(11).
    PMID: 27792171
    Vitamin E has been recognized as an essential vitamin since their discovery in 1922. Although the functions of tocopherols are well established, tocotrienols have been the unsung heroes of vitamin E. Due to their structural differences, tocotrienols were reported to exert distinctive properties compared to tocopherols. While most vegetable oils contain higher amount of tocopherols, tocotrienols were found abundantly in palm oil. Nature has made palm vitamin E to contain up to 70% of total tocotrienols, among which alpha-, gamma- and delta-tocotrienols are the major constituents. Recent advancements have shown their biological properties in conferring protection against cancer, cardiovascular diseases, neurodegeneration, oxidative stress and immune regulation. Preclinical results of these physiological functions were translated into clinical trials gaining global attention. This review will discuss in detail the evidence in human studies to date in terms of efficacy, population, disease state and bioavailability. The review will serve as a platform to pave the future direction for tocotrienols in clinical settings.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  16. pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells
    Mishra RK, Ramasamy K, Ahmad NA, Eshak Z, Majeed AB
    J Mater Sci Mater Med, 2014 Apr;25(4):999-1012.
    PMID: 24398912 DOI: 10.1007/s10856-013-5132-x
    Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC50 = 110-190 μg ml(-1)) and HCT116 (IC50 = 210-390 μg ml(-1))] but not human skin fibroblast cells [BJ (CRL2522); IC50 ≥ 1000 μg ml(-1)]. This implies that the copolymer hydrogels (1-4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  17. Disposition and tissue distribution of imatinib in a liposome formulation after intravenous bolus dose to mice
    Moo KS, Radhakrishnan S, Teoh M, Narayanan P, Bukhari NI, Segarra I
    Yao Xue Xue Bao, 2010 Jul;45(7):901-8.
    PMID: 20931790
    Imatinib is an efficacious anticancer drug with a spectrum of potential antitumour applications limited by poor biodistribution at therapeutic concentrations to the tissues of interest. We assess the pharmacokinetic and tissue distribution profile of imatinib in a liposome formulation. Its single dose (6.25 mg x kg(-1)) in a liposome formulation was administered iv to male mice. Imatinib concentration was measured in plasma, spleen, liver, kidney and brain using a HPLC assay. Non-compartmental pharmacokinetic approach was used to assess the disposition parameters. The plasma disposition profile was biphasic with a plateau-like second phase. The AUC(0-->infinity) was 11.24 microg x h x mL(-1), the elimination rate constant (k(el)) was 0.348 h(-1) and the elimination half life (t(1/2)) was 2.0 h. The mean residence time (MRT) was 2.59 h, V(SS) was 1.44 L x kg(-1) and clearance was 0.56 L x h x kg(-1). Liver achieved the highest tissue exposure: CMAX = 18.72 microg x mL(-1); AUC(0-->infinity)= 58.18 microg x h x mL(-1) and longest t(1/2) (4.29 h) and MRT (5.31 h). Kidney and spleen AUC(0-->infinity) were 47.98 microg x h x mL(-1) and 23.46 microg x h x mL(-1), respectively. Half-life was 1.83 h for the kidney and 3.37 h for the spleen. Imatinib penetrated into the brain reaching approximately 1 microg x g(-1). Upon correction by organ blood flow the spleen showed the largest uptake efficiency. Liposomal imatinib presented extensive biodistribution. The drug uptake kinetics showed mechanism differences amongst the tissues. These findings encourage the development of novel imatinib formulations to treat other cancers.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  18. Fulltext Mathematical Based Calculation of Drug Penetration Depth in Solid Tumors
    Namazi H, Kulish VV, Wong A, Nazeri S
    Biomed Res Int, 2016;2016:8437247.
    PMID: 27376087 DOI: 10.1155/2016/8437247
    Cancer is a class of diseases characterized by out-of-control cells' growth which affect cells and make them damaged. Many treatment options for cancer exist. Chemotherapy as an important treatment option is the use of drugs to treat cancer. The anticancer drug travels to the tumor and then diffuses in it through capillaries. The diffusion of drugs in the solid tumor is limited by penetration depth which is different in case of different drugs and cancers. The computation of this depth is important as it helps physicians to investigate about treatment of infected tissue. Although many efforts have been made on studying and measuring drug penetration depth, less works have been done on computing this length from a mathematical point of view. In this paper, first we propose phase lagging model for diffusion of drug in the tumor. Then, using this model on one side and considering the classic diffusion on the other side, we compute the drug penetration depth in the solid tumor. This computed value of drug penetration depth is corroborated by comparison with the values measured by experiments.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics*
  19. Fulltext Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect
    Rahman HS, Rasedee A, How CW, Abdul AB, Zeenathul NA, Othman HH, et al.
    Int J Nanomedicine, 2013;8:2769-81.
    PMID: 23946649 DOI: 10.2147/IJN.S45313
    Zerumbone, a natural dietary lipophilic compound with low water solubility (1.296 mg/L at 25°C) was used in this investigation. The zerumbone was loaded into nanostructured lipid carriers using a hot, high-pressure homogenization technique. The physicochemical properties of the zerumbone-loaded nanostructured lipid carriers (ZER-NLC) were determined. The ZER-NLC particles had an average size of 52.68 ± 0.1 nm and a polydispersity index of 0.29 ± 0.004 μm. Transmission electron microscopy showed that the particles were spherical in shape. The zeta potential of the ZER-NLC was -25.03 ± 1.24 mV, entrapment efficiency was 99.03%, and drug loading was 7.92%. In vitro drug release of zerumbone from ZER-NLC was 46.7%, and for a pure zerumbone dispersion was 90.5% over 48 hours, following a zero equation. Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay in human T-cell acute lymphoblastic leukemia (Jurkat) cells, the half maximal inhibitory concentration (IC50) of ZER-NLC was 5.64 ± 0.38 μg/mL, and for free zerumbone was 5.39 ± 0.43 μg/mL after 72 hours of treatment. This study strongly suggests that ZER-NLC have potential as a sustained-release drug carrier system for the treatment of leukemia.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
  20. Fulltext Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities
    Ruman U, Fakurazi S, Masarudin MJ, Hussein MZ
    Int J Nanomedicine, 2020;15:1437-1456.
    PMID: 32184597 DOI: 10.2147/IJN.S236927
    The development of therapeutics and theranostic nanodrug delivery systems have posed a challenging task for the current researchers due to the requirement of having various nanocarriers and active agents for better therapy, imaging, and controlled release of drugs efficiently in one platform. The conventional liver cancer chemotherapy has many negative effects such as multiple drug resistance (MDR), high clearance rate, severe side effects, unwanted drug distribution to the specific site of liver cancer and low concentration of drug that finally reaches liver cancer cells. Therefore, it is necessary to develop novel strategies and novel nanocarriers that will carry the drug molecules specific to the affected cancerous hepatocytes in an adequate amount and duration within the therapeutic window. Therapeutics and theranostic systems have advantages over conventional chemotherapy due to the high efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimum side effects. These nanocarriers possess high drug accumulation in the tumor area while minimizing toxic effects on healthy tissues. This review focuses on the current research on nanocarrier-based therapeutics and theranostic drug delivery systems excluding the negative consequences of nanotechnology in the field of drug delivery systems. However, clinical developments of theranostics nanocarriers for liver cancer are considered outside of the scope of this article. This review discusses only the recent developments of nanocarrier-based drug delivery systems for liver cancer therapy and diagnosis. The negative consequences of individual nanocarrier in the drug delivery system will also not be covered in this review.
    Matched MeSH terms: Antineoplastic Agents/pharmacokinetics
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