Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 59 , Issue 2
Showing 1-25 articles out of 25 articles from the selected issue
Review
  • Keiji Yamamoto, Waree Limwikrant, Kunikazu Moribe
    Type: Review
    2011 Volume 59 Issue 2 Pages 147-154
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR.
    Download PDF (1501K)
Regular Articles
  • Ahmad Khaled Bani-Jaber, Mahmoud Yousef Alkawareek, Jozef Jawad Al-Gou ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 155-160
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The aim of this study was to evaluate the influence of Na-bicarbonate as an effervescent agent on the floating and sustained-release characteristics in 0.1 M HCl of tablets made of Eudragit E PO (EE) and/or Eudragit L-100-55 (EL) as matrix formers at different EE : EL weight ratios: 0 : 100, 25 : 75, 50 : 50, 75 : 25, and 100 : 0. The tablets were made by direct compression utilizing metronidazole as a model drug. Effervescent tablets with 50EE/50EL (w/w) showed the best floating and sustained drug release properties in the dissolution medium. The corresponding noneffervescent tablets were nonfloating and showed significantly faster drug release. Effervescent tablets with single polymers showed an immediate drug release pattern. These results were explained by Fourier-transform infrared spectroscopy and elemental analysis, which showed strong evidence of interpolyelectrolyte complexation between EE and EL when they were exposed to 0.1 M HCl as an effervescent hybrid matrix, but not as a noneffervescent hybrid matrix. The role of Na-bicarbonate in allowing EE–EL complexation during dissolution was explained as due to raising the pH around EL particles for sufficient polymer ionization and ionic-interaction with the ionized EE.
    Download PDF (974K)
  • Claudia Pérez, José Becerra, Paula Manríquez-Nava ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 161-165
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The electrophysiological characterization of sesquiterpene lactones from Coriaria ruscifolia subsp. ruscifolia has been tested on hippocampal neurons. The results for glycinergic rat hippocampal transmission and native γ-aminobutyric acid (GABA)ergic transmission on neurons (13DIV) are remarkably different for tutin, coriamyrtin, and dihydrotutin, being tutin the most potent inhibitor and dihydrotutin the least potent one. To understand the applied mechanism of action, we discuss the structural and electronic requirements for inhibitory activity by these sesquiterpene lactones when modulating receptors of the central nervous system. The structural and electrostatic properties of these compounds were compared to those of more active metabolites like picrotoxins. The minimal energy level of these structures was calculated and then optimized at the ab initio B3LYP/DGDZVP level of theory using Gaussian 03W software. This allowed calculation of the corresponding vibrational circular dichroism spectrum of coriamyrtin which rendered the molecular absolute configuration after comparison with an experimental spectrum. These results are consistent with those from studies of other models that provide the basis for the activity on the presence of the lactone at carbons 3 and 5, the presence of the hydroxyl group at position 6, and the different electronic distributions observed in tutin and coriamyrtin. The latter has an isopropenyl moiety at carbon 4 in contrast to the dihydrotutin isopropyl group at the same position, which could explain the difference in activity between dihydrotutin and tutin or coriamyrtin. The presence of the hydroxyl group at carbon 2 is not decisive since this functionality is present in tutin, the most active compound, and in dihydrotutin, the less active one.
    Download PDF (1170K)
  • Geeta Budige, Muralidhar Reddy Puchakayala, Shobha Rani Kongara, Anren ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 166-171
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    New tetradentate N2O2 donor Schiff bases and their mononuclear Co(II), Ni(II), Cu(II), and Pd(II) complexes were synthesized and characterized extensively by IR, 1H-, 13C-NMR, mass, ESR, conductivity measurements, elemental and thermal analysis. Specifically the magnetic and electronic spectral measurements demonstrate the octahedral structures of cobalt(II), nickel(II) complexes and square planar geometries of copper(II), palladium(II) complexes. All the ligands and complexes were screened for their in vitro antibacterial activity against two Gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus) and two Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia). In this study, Pd(II) complexes exhibited potent antibacterial activity against B. subtilis, S. aureus whereas other metal complexes also exerted good activity towards all tested strains even than standard drugs streptomycin and ampicillin.
    Download PDF (558K)
  • Chi-Hsien Liu, Fu-Yen Chang
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 172-178
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Microemulsions have received great attention for applications in transdermal drug delivery. The use of curcumin for treating various skin diseases like scleroderma, psoriasis, and skin cancer was extensively reported. The solubility of curcumin in various oils, surfactants, and cosurfactants was studied herein in order to find the optimal components for a transdermal delivery vehicle. Microemulsion systems composed of eucalyptol, polysorbate 80, ethanol, and water were developed as transdermal delivery vehicles for curcumin. Effects of the microemulsion composition on transdermal curcumin delivery were studied using Franz diffusion cells. The transdermal curcumin flux, permeability coefficient, and enhancement ratio were analyzed to evaluate the effects of eucalyptol/water ratios in the microemulsions. Pseudo-ternary phase diagrams of the eucalyptol microemulsions with various surfactant/cosurfactant ratios (1 : 1—1 : 3) were constructed to investigate their phase behaviors. Conductivity, interfacial tension, size, and viscosity data of the microemulsions were used to characterize the physicochemical properties of transdermal vehicles. The influence of the microemulsions on skin histology and on the delivery route was analyzed using hematoxylin/eosin staining and confocal laser scanning microscopy. In conclusion, microemulsions were successfully developed for transdermal curcumin delivery after screening various components and adjusting the oil/water ratios. The curcumin permeation rate of the microemulsion developed was 15.7-fold higher than that of the control (eucalyptol only). These results indicate that an eucalyptol microemulsion system is a promising tool for the percutaneous delivery of curcumin.
    Download PDF (1218K)
  • Oldřich Pytela, Věra Klimešová
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 179-184
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    A set of 1160 minimum inhibitory concentration (MIC) values evaluating effect of substitution on the antimycobacterial activity of the previously published 2-(substituted benzyl)sulfanyl benzimidazoles, benzoxazoles, and benzothiazoles has been analyzed by the methods of multidimensional analysis (exploratory analysis, 2D-nonlinear mapping (NLM), principal component analysis (PCA), factor analysis (FA), multiple linear regression (MLR)). The antimycobacterial activity of 2-(subst. benzyl)sulfanyl derivatives of benzimidazole (BIM), 5-methylbenzimidazole (5-Me-BIM), benzoxazole (BOZ), and benzothiazole (BTZ) increased in the order of BTZ<BOZ~BIM<5-Me-BIM. The sensitivity of particular strains towards these compounds decreased in the order of Mycobacterium kansasii 6509/96, M. avium My 330/88, M. kansasii My 235/80, and M. tuberculosis My 331/88. In general, derivatives with 3-CSNH2, 2,4-(NO2)2, 4-CSNH2, 3,5-(NO2), and partially 4-NO2 substituents possess the highest antimycobacterial activity. The effect of substitution was also described quantitatively with good correlation factor R of 0.79—0.88. The log MIC values depended with a negative slope on the Hammett substituent constants σ or molar refractions MR and, for the given set of substituents, were dominantly raised with increasing log P value and partially lowered with (log P)2 or σ×Δ log P. The derivatives featuring high polarizability, low lipophilicity and electron-withdrawing subtituents showed the highest antimycobacterial activity. The dependence on the steric substituent constant v was not statistically significant and, therefore, the ortho effect was most probably not important.
    Download PDF (850K)
  • Shukla Raj Kumar, Trivedi Piyush, Ramteke Suman, Tiwari Akanksha
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 185-190
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    In the present work cross-linked guar gum microspheres were prepared for colon specific delivery of ornidazole. Development and optimization of guar gum microspheres for colonic drug delivery was carried out using a 24 factorial design based on four independent variables. Microspheres were prepared by emulsification method using glutaraldehyde as cross-linking agent. Morphology and surface characteristics of the formulations were determined by scanning electron microscopy. Particle size of the guar gum microspheres was determined by particle size analyzer. In vitro drug-release studies were performed in conditions simulating stomach-to-colon transit in the presence and absence of rat cecal contents. Only a small fraction of drug was released at acidic pH; however, the release of drug was found to be higher in the presence of rat cecal contents, indicating the susceptibility of guar gum matrix to colonic enzymes released from rat cecal contents. The significance of differences was evaluated by analysis of variance (ANOVA). Differences were considered statistically significant at p<0.05.
    Download PDF (1061K)
  • Murari Lal Soni, Kamta Prasad Namdeo, Sunil Kumar Jain, Manish Gupta, ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 191-195
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The purpose of this research work was to develop and evaluate a chronotherapeutic based colon-targeted drug delivery system of theophylline (THEO) exploiting pH-enzyme sensitive property for the prevention of episodic attack of asthma in early morning. Guar gum microspheres of theophylline were prepared by emulsification technique. Coating of microspheres was performed using solvent evaporation method with pH sensitive Eudragit® polymers. The particle size and surface morphology, entrapment efficiency and degree of swelling of microspheres were examined. The in vitro drug release studies were performed in pH progression medium and also in the presence of 2% rat caecal content. Theophylline was efficiently microencapsulated in guar gum microspheres at different polymer concentrations (1—4%). Fourier transform infrared (FT-IR)-spectroscopy confirmed the intermolecular interactions between guar gum and glutaraldehyde. Coating of guar gum microspheres by Eudragit led to decelerate the in vitro drug release of THEO. Moreover in vitro drug release studies also performed with 2% rat caecal content showed marked increment in drug release. The controlled release of THEO after a lag time was achieved with developed formulation for chronotherapeutic delivery. The pH dependent solubility behavior of Eudragit and gelling properties of guar gum are found to be responsible for delaying the release.
    Download PDF (1001K)
  • Tamae Uchida, Takanori Kanazawa, Yuuki Takashima, Hiroaki Okada
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 196-201
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Topical use of small interfering RNA (siRNA) as a therapeutic nucleic acid is increasingly studied for the treatment of skin diseases and for the improvement of skin properties. However, naked siRNA transdermal delivery is limited by its low stability in the body and low permeability into target cells. This is due to various skin barriers such as the stratum corneum that has multiple lipid bilayers and epidermal layers that have tight junctions. In this study, we investigate non-invasive transdermal siRNA delivery using two functional peptides: AT1002, which is a tight junction modulator and 6-mer synthetic peptide belonging to a novel class of compounds that reversibly increases paracellular transport of molecules across the epithelial barrier; and Tat, which is a cell-penetrating peptide applicable as a transdermal siRNA delivery enhancer. We examined whether expression of the tight junction protein zonula occludens protein 1 (ZO-1) was detected in mouse skin applied with AT1002. Additionally, siRNA stabilities for RNaseA using Tat and AT1002 were assessed. We also determined the intradermal delivery efficiency of siRNA using functional peptides by confocal laser microscopy of fluorescently labeled siRNA in mouse skin. We found that the Tat analog and AT1002 strongly increased siRNA stability against RNaseA. In addition, ZO-1 disappeared from the skin after treatment with AT1002, yet recovered with time after washing. Finally, we also found that Tat and AT1002 peptides accelerate transdermal siRNA delivery both widely and effectively. Thus, combination of Tat and AT1002 is expected to be a transdermal delivery enhancer of siRNA.
    Download PDF (4668K)
  • Ko Tanaka, Takanori Kanazawa, Takaya Ogawa, Yumiko Suda, Yuuki Takashi ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 202-207
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    We have engineered a novel, non-viral, multifunctional gene vector (STR-CH2R4H2C) that contained stearoyl (STR) and a block peptide consisting of Cys (C), His (H), and Arg (R). STR-CH2R4H2C can form a stable nano-complex with plasmid DNA (pDNA) based on electronic interactions and disulfide cross linkages. In this study, we evaluated the efficacy of STR-CH2R4H2C as a gene vector. We first determined the optimal weight ratio for STR-CH2R4H2C/pDNA complexes. The complexes with a weight ratio of 50 showed the highest transfection efficacy. We also examined the transfection efficacy of STR-CH2R4H2C/pDNA complexes with or without serum and compared STR-CH2R4H2C/pDNA transfection efficacy with that of Lipofectamine. Even in the presence of serum, STR-CH2R4H2C showed higher transfection efficacy than did Lipofectamine. In addition, we determined the mechanism of transfection of the STR-CH2R4H2C/pDNA complexes using various cellular uptake inhibitors and evaluated its endosomal escape ability using chloroquine. Macropinocytosis was main cellular uptake pathway of STR-CH2R4H2C/pDNA complexes. Our results suggested that STR-CH2R4H2C is a promising gene delivery system.
    Download PDF (824K)
  • Yuya Horinouchi, Koichiro Tsuchiya, Chiaki Taoka, Soichiro Tajima, Yos ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 208-214
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Recently, increasing evidence suggests that the antihypertensive drug nifedipine acts as a protective agent for endothelial cells, and that the activity is unrelated to its calcium channel blocking. Nifedipine is unstable under light and reportedly decomposes to a stable nitrosonifedipine (NO-NIF). NO-NIF has no antihypertensive effect, and it has been recognized as a contaminant of nifedipine. The present study for the first time demonstrated that NO-NIF changed to a NO-NIF radical in a time-dependent manner when it interacted with human umbilical vein endothelial cells (HUVECs). The electron paramagnetic resonance (EPR) signal of NO-NIF radicals in HUVECs showed an asymmetric pattern suggesting that the radicals were located in the membrane. The NO-NIF radicals had radical scavenging activity for 1,1-diphenyl-2-picrylhydrazyl, whereas neither NO-NIF nor nifedipine did. In addition, the NO-NIF radical more effectively quenched lipid peroxides than NO-NIF or nifedipine. Furthermore, NO-NIF attenuated the superoxide-derived free radicals in HUVECs stimulated with LY83583, and suppressed iron-nitrilotriacetic acid (Fe-NTA)-induced cytotoxicity in rat pheochromocytoma (PC12) cells. Our findings suggest that NO-NIF is a candidate for a new class of antioxidative drugs that protect cells against oxidative stress.
    Download PDF (787K)
  • Nagahisa Yamaoka, Hidehiko Kodama, Yuko Izuhara, Toshio Miyata, Kanji ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 215-224
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Novel anthranilic acid derivatives having substituted N-acyl side chains were designed and synthesized for evaluation as plasminogen activator inhibitor-1 (PAI-1) inhibitors. Compounds with a 4-diphenylmethyl-1-piperazinyl moiety on the acyl side chains in general exhibited potent in vitro PAI-1 inhibitory activity and good pharmacokinetic profiles after oral administration in rats. Compound 16f (TM5275) was identified as a promising candidate for further pharmacological evaluation.
    Download PDF (809K)
  • Jun Luo, Jun-Song Wang, Xiao-Bing Wang, Jian-Guang Luo, Ling-Yi Kong
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 225-230
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Nine new phragmalin-type limonoid orthoesters, tabulalides F—N (19), together with three known compounds, tabulalides C and D, and tabularisin N (1012), were isolated from the stem bark of Chukrasia tabularis var. velutina. Extensive spectroscopic technologies were applied to elucidate the structures of these new compounds, including the application of circular dichroism (CD) exciton chirality method for the determination of the absolute configurations of 1 and 2. Tabulalide F (1) has a rare orthoisobutylate moiety in phragmalin-type limonoid orthoesters. These compounds were evaluated for cytotoxic activity against five human cancer cell lines in vitro. Tabulalide G (2) exhibts moderate cytotoxic activity against MCF-7 with IC50 value of 20.4 μmol/l, and other compounds have weak inhibitory effects on the growth of tested tumor cells.
    Download PDF (858K)
  • Ying-hui Duan, Yi Dai, Guang-hui Wang, Hai-feng Chen, Hao Gao, Jie-bo ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 231-234
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Two new xanthone glycosides, namely pruniflorosides A and B (1, 2), a new benzophenone glycoside, prunifloroside C (3), and a new xanthone, pruniflorone S (4) were isolated from the stems of Cratoxylum formosum ssp. pruniflorum, along with six known xanthones (510). Their structures were determined on the basis of extensive spectroscopic analysis. In addition, their retinoid X receptor α (RXRα) transcriptional activities were evaluated in vitro.
    Download PDF (617K)
  • Yuka Sugamura, Makiko Fujii, Sayaka Nakanishi, Ayako Suzuki, Yusuke Sh ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 235-238
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 μm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds.
    Download PDF (4165K)
  • Naohito Abe, Tetsuro Ito, Masayoshi Oyama, Ryuichi Sawa, Yoshikazu Tak ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 239-248
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Investigation of the highly polar chemical constituents in the stem of Hopea parviflora (Dipterocarpaceae) resulted in the isolation of four new resveratrol derivatives, hopeasides A and B (1, 2) (resveratrol pentamers), C (3) (resveratrol trimer), and D (4) (resveratrol dimer) together with nine known resveratrol oligomers (513). The new structures have a common partial structure of the 1-hydroxy-1-(3,5-dihydroxy-2-C-glucopyranosylphenyl)-2-(4-hydroxyphenyl)ethane-2-yl group after oxidative condensation of (E)-resveratrol-10-C-β-glucopyranoside (14). The structures were determined by spectroscopic analysis including 2D-NMR and computer-aided molecular modeling. The biogenetic relationship of the isolates and NMR characteristics caused by steric hindrance are also discussed in this paper.
    Download PDF (1627K)
  • Yuu Shibano, Shiwori Taki, Aoi Miyamoto, Kazuo Uchikura
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 249-253
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    We studied the detection of drug-metabolizing enzyme inhibitiors using column-switching high performance liquid chromatography with tris(2,2′-bipyridine)ruthenium(II) (Ru(bpy)32+)-electrogenerated chemiluminescence detection. This can be applied to evaluate the genetic diversity concerning the ability of cytochrome P450 (CYP) 2D6 to metabolize drug in vitro. We demonstrated the ability of CYP2D6 to enable us to examine drugs metabolizing enzyme inhibition with high performance and sensitivity. This method can be applied to investigate metabolite inhibitors of CYP2D6 in vitro and in vivo. Thus, Metixene was found to be a potential CYP2D6 inhibitor.
    Download PDF (723K)
  • Sayed Imam Mohamed Zayed
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 254-259
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Carbon paste electrodes for pancuronium bromide was prepared based on ion association complexes of pancuronium bromide with sodium tetraphenylborate (NaTPB) or ammonium reineckate using dibutyl phthalate as solvent mediator and tetradodecylammonium tetrakis-(4-chlorophenyl)borate (ETH 500) as lipophilic additive. The sensors showed a near-Nernstian slope of 28.1 mV concentration decade−1 at 25 °C within the concentration range 6.31×10−6—1.00×10−2 M in case of pancuronium-tetraphenylborate electrode and 26.6 mV concentration decade−1 in the concentration range 5.66×10−5—1.00×10−2 M in case of pancuronium-reineckate electrode. The sensors were successfully applied for the potentiometric determination of pancuronium bromide in pharmaceutical preparation and biological fluids in batch and flow injection conditions.
    Download PDF (713K)
  • Xi-ming Xu, Yan-song Wang, Rong-ying Chen, Chun-lai Feng, Feng Yao, Sh ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 260-265
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The aim of this work was to prepare tetracycline-loaded solid lipid nanoparticles (Tet-SLN), and to evaluate the potential of these colloidal carriers for subcutaneous injection. Tet-SLN was prepared by microemulsion method and the preparation conditions were optimized by ternary phase diagram. At optimized process conditions, lyophilized Tet-SLN showed spherical particles with a mean diameter of 87.2±46.9 nm and a negative zeta potential of −6.69 mV, up to 1.7% tetracycline drug content was achieved after loading. In vitro release test showed a biphasic release profile for Tet-SLN and more than 80% of the drug was liberated from Tet-SLN in 48 h. After subcutaneous injection of Tet-SLN to mice, a considerable sustained release was observed; tetracycline in blood could be detected lasting 36 h, and lower concentrations of tetracycline in all tissues tested compared to the free tetracycline solution were observed. In conclusion, Tet-SLN can be prepared well by microemulsion method and subcutaneous injection of SLN provide a new perspective for drug sustained release.
    Download PDF (1844K)
  • Yi-Ping Fang, Yin-Ku Lin, Yu-Han Su, Jia-You Fang
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 266-271
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    Tryptanthrin is an ancient medicine which recently was also found to have a function of downregulating multidrug resistance (MDR). However, tryptanthrin is insoluble in water, which limits its availability for delivery into cancer cells. There is a need to improve delivery systems to increase the inhibition of MDR. The aim of this study was to employ nanoparticles encapsulating tryptanthrin to improve the delivery and promote the sustained release of this drug. The approach was to encapsulate tryptanthrin in various nanoparticles, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid emulsions (LEs). We compared the particle size and zeta potential of these nanoparticles, and evaluated the partitioning behavior of tryptanthrin in them. We also determined the release kinetics of tryptanthrin from these nanoparticles. Moreover, cellular cytotoxicity toward and uptake of tryptanthrin-loaded nanoparticles by human breast cancer cells were determined. We found that the mean particle size of NLCs was lower, and the partition coefficient was higher than those of SLNs, and an increased tryptanthrin release rate was found with the NLC delivery system. NLCs achieved the sustained release of tryptanthrin without an initial burst. In particular, the NLC-C formulation, composed of a mixture of Compritol and squalene as the core materials, showed the highest release rate and cytotoxic effect. Confocal laser scanning microscopic images confirmed drug internalization into cells which enhanced the endocytosis of the particles. These results suggested that NLCs can potentially be exploited as a drug carrier for topical or intravenous use in the future.
    Download PDF (1250K)
  • Ramesh Chand Nagarwal, Paras Nath Singh, Shri Kant, Pralay Maiti, Jaya ...
    Type: Regular Article
    2011 Volume 59 Issue 2 Pages 272-278
    Published: February 01, 2011
    Released: February 01, 2011
    JOURNALS FREE ACCESS
    The aim of this investigation was to develop 5-fluorouracil (5-FU) loaded chitosan nanoparticles (CH-DNPs) for ophthalmic delivery. CH-DNPs were fabricated by ionotropic gelation mechanism using chitosan (CH) and a polyanion (TPP). The nanoparticles were smooth and spherical, confirmed by scanning electron microscopy (SEM) and atomic force microscope (AFM). CH/TPP mass ratio and TPP significantly changed the particles size morphology and encapsulation efficiency. The nanoparticles size ranged from approximately 114 to 192 nm and had a positive zeta potential (30±4 mV). The encapsulation efficiency, loading capacity and recovery of DNPs were 8.12—34.32%, 3.14—15.24% and 24.22 to 67% respectively. Physical characterization was done by Fourier transform infrared (FT-IR) and X-ray diffraction (XRD). No interaction was observed in between drug and polymer and crystallinity of drug was not changed in drug loaded nanoparticles. In-vitro release study of DNPs showed diffusion controlled release. Bioavailability study of batch CS9 was studied in rabbit eye and compare to 5-FU solution. 5-FU level was significantly higher in aqueous humor of rabbit eye. Ocular tolerance was studied in the eye of New Zealand rabbits and tested formulation was non-irritant with no sign of inflammation.
    Download PDF (2921K)
Notes
feedback
Top