ALBERT

All Library Books, journals and Electronic Records Telegrafenberg

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Hydroxypropyl-β-Cyclodextrin Increases the Aqueous Solubility and Stability of Pilocarpine Prodrugs (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 1371-1375 
    Details
    ISSN: 1573-904X
    Keywords: prodrug ; bispilocarpic acid diester ; hydroxypropyl-β-cyclodextrin ; inclusion complex ; solubility ; stability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility and stability of two lipophilic bispilocarpine prodrugs were investigated at pH 7.4. Methods. The solubility of prodrugs was studied by phase-solubility method (0–72.5 mM HP-β-CD). The stability of one of the prodrugs was investigated as a function of temperature (40°C–70°C) and HP-β-CD concentration (0–72.5 mM). The apparent rate constants (k 1, k 2) for degradation of prodrug in 1:1 and 1:2 inclusion complexes and apparent stability constants (K 1:1, K l:2) were calculated by the curve-fitting method. Results. The phase-solubility diagrams were classified as Ap-type and the apparent stability constants (K l:l, K l:2) for 1:1- and 1:2-inclusion complexes were calculated to be 143–815 M−l and 29–825 M−1, respectively. The stability of prodrug increased as a function of HP-β-CD concentration over the studied temperature range. The shelf-life (t 90%, calculated by the Arrhenius equation) of the prodrug in 72.5 mM HP-β-CD solution increased 5.1-fold and 6.1-fold at 25°C and 4°C, respectively. Conclusions. The solubility of the prodrugs was shown to increase markedly in phase-solubility studies. The degradation rate of prodrug in stability studies was shown to be slower in the l:2-complex than in the l:l-complex and the relative amounts of complex species were found to be dependent on CD concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016290127371
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Comparison of Cell Proliferation and Toxicity Assays Using Two Cationic Liposomes (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1127-1131 
    Details
    ISSN: 1573-904X
    Keywords: cell toxicity assays ; cell proliferation assays ; cationic liposomes ; CaSki cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The present study compares different cytotoxicity and cell proliferation assays including cell morphology, mitochondrial activity, DNA synthesis, and cell viability and toxicity assays. CaSki cells were exposed to two cationic liposomal preparations containing dimethyldioctadecyl-ammonium bromide (DDAB), dioleoylphosphatidylethanolamine (DOPE) and a commercial transfection-reagent DOTAP(N[l-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium-methylsulfate). The results provided by these assays were similar. However, the lactate dehydrogenase assay was more sensitive in measuring early damages of cell membranes than the Trypan blue assay. Also, cell morphology showed early toxic changes, such as cytoplasmic vacuolization and cell shrinking, and it should be included with such toxicity evaluations. DDAB:DOPE was more toxic than DOTAP. The cells treated with DOTAP at 10 µM were surviving as well as the control cells, while DOTAP at 40 µM and DDAB: DOPE at 10 µM had slight toxic effects on CaSki cells. The most toxic effects were seen in CaSki cells after treatment with DDAB: DOPE at 40 µM.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018932714745
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Evaluation of Cytotoxicity of Various Ophthalmic Drugs, Eye Drop Excipients and Cyclodextrins in an Immortalized Human Corneal Epithelial Cell Line (1998)
    Springer
    Pharmaceutical research 15 (1998), S. 1275-1280 
    Details
    ISSN: 1573-904X
    Keywords: cell culture ; corneal epithelium ; cyclodextrins ; cytotoxicity ; immortalized cell line ; ocular irritation ; ophthalmic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. An immortalized human corneal epithelial cell line (HCE) was tested as a screening tool for prediction of topical ocular irritation/ toxicity by pharmaceuticals. Methods. Effects of various drugs, excipients and cyclodextrins (CDs) on viability of HCE cells were evaluated using two in vitrocytotoxicity tests, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) dye reduction assay and propidium iodide assay. Results. Mitochondrion-based MTT test was a more sensitive indicator of cytotoxicity than the plasma membrane-based propidium iodide test. The tests revealed following cytotoxic rankings for ophthalmic drugs: dipivefrin 〉 timolol 〉 pilocarpine ≈ dexamethasone; for excipients: benzalkonium chloride (BAC) 〉 sodium edetate (NA2EDTA) 〉 poly-vinyl alcohol (PVA) 〉 methylparaben; and for CDs: α-CD 〉 dimethyl-β-cyclodextrin (DM-β-CD) 〉 sulfobutyl ether (β-cyclodextrin ((SBE)7m-β-CD) ≈ hydroxypropyl-β-cyclodextrin (HP-β-CD) 〉 γ-CD. In consideration of the in vivoclinical situation, the short exposure time (5 min) is more relevant even though toxic effects of some test substances were seen only after longer exposure times (30 and 60 min). Conclusions. Immortalized HCE cells are a promising tool for rapid cytotoxicity assays of ocular medications. The cell line is potentially useful in predicting the in vivocorneal toxicity of ocularly applied compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1011956327987
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Ocular Absorption and Irritation of Pilocarpine Prodrug Is Modified with Buffer, Polymer, and Cyclodextrin in the Eyedrop (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 529-533 
    Details
    ISSN: 1573-904X
    Keywords: pilocarpine ; prodrug ; bispilocarpic acid diester ; miotic activity ; irritation ; ocular absorption ; 2-hydroxypropyl-β-cyclodextrin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O′-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl-β-cyclodextrin (HPCD) was included at concentrations 5,10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the pro-drug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016297728396
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Effect of Liposomal and Free Bisphosphonates on the IL-1β, IL-6 and TNFα Secretion from RAW 264 Cells in Vitro (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 916-922 
    Details
    ISSN: 1573-904X
    Keywords: bisphosphonates ; liposomal drug delivery ; macrophages ; proinflammatory cytokines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. In order to evaluate the possible antiinflammatory action of bisphosphonates, the effect of the drugs on the secretion of proinflammatory cytokines (IL-lβ, IL-6 and TNFα) from macrophages was studied. Liposomes or high concentration of extracellular calcium was used to enhance the intracellular delivery of bisphosphonates. Methods. RAW 264 cells were used as macrophage model, and they were induced with lipopolysaccharide to produce the cytokines. The cytokine concentrations in the culture supernatants were measured with time-resolved fluoroimmunoassay. Results. As a free drug, clodronate and pamidronate, but not etidronate, inhibited LPS-stimulated secretion of the cytokines from macrophage-like RAW 264 cells. Low concentrations of pamidronate, however, induced the IL-6 secretion, and the cytokine inhibitory action at the higher concentrations of pamidronate was attributed to cytotoxicity of the compound. The cytokine induction or toxic effects were not observed with clodronate or etidronate. When the drugs were encapsulated in negatively charged unilamellar liposomes, the inhibitory potency of both clodronate and etidronate enhanced by a factor of 10-20, while that of pamidronate was not increased. The complex formation of bisphosphonates with extracellular calcium, although enhancing the uptake of the compounds by macrophages, did not considerably increase their cytokine inhibitory potency. Conclusions. Bisphosphonates have inhibitory action on cytokine secretion by macrophages. The non-cytotoxic cytokine inhibition by liposome encapsulated clodronate could be beneficial in local inflammatory diseases, where the inflammation is sustained by the excessive amounts of inflammatory cytokines produced by activated macrophages.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016281608773
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Effects of Topical alpha-Substituted Anandamides on Intraocular Pressure in Normotensive Rabbits (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1738-1743 
    Details
    ISSN: 1573-904X
    Keywords: anandamides ; intraocular pressure ; cyclodextrin ; indomethacin ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. Anandamides have been observed to lower intraocular pressure in the rabbit eye, preceded by a period of hypertension. Amidases are thought to catabolize these compounds into their component parts, including arachidonic acid. Direct application of arachidonic acid has been observed to cause a marked rise of intraocular pressure. Thus, anandamide analogs resistant to catabolism were thought possibly devoid of this initial hypertension, and their effects on rabbit IOP investigated. Methods. A series of chiral alpha-substituted anandamides were synthesized and studied for their effect on the intraocular pressure (IOP) of normotensive pigmented rabbits. Each test compound was dissolved in an aqueous 2-hydroxypropyl-β-cyclodextrin solution (containing 3% polyvinyl alcohol) and administered (62.5 μg) unilaterally to the eye. Results. The most promising compounds caused a statistically significant reduction of IOP (vs. vehicle) in the treated eyes. Of these, the R-alpha-isopropyl compound exhibited the best activity tested. Unlike the alpha-unsubstituted analogs previously studied, hypotensive effects were not preceded by an initial elevation of IOP and indomethacin pre-treatment (12.5 mg, s.c.) did not eliminate the IOP response, as demonstrated by administered R-alpha-isopropyl anandamide. Conclusions. Catabolism of alpha-unsubstituted anandamides may account for their observed intraocular hypertensive effects. The physiological mechanism by which alpha-substituted anandamides work apparently differs from that of the more easily metabolized alpha-unsubstituted compounds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012131929940
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    Controlled Ocular Timolol Delivery: Systemic Absorption and Intraocular Pressure Effects in Humans (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 1278-1282 
    Details
    ISSN: 1573-904X
    Keywords: timolol ; intraocular pressure ; systemic absorption ; controlled release ; ocular drug delivery
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Timolol eyedrops may cause systemic side-effects in glaucoma patients due to absorption of the drug into systemic circulation. In a previous study, timolol concentrations in plasma were reduced if timolol was administered in ocular inserts instead of eyedrops. We compared the intraocular pressure lowering effect and systemic absorption of timolol inserts to those of 0.5 % timolol eyedrops in humans. Inserts of silicone tubing released 90.3 ± 13.9 µg of timolol in 24 hours in vivo. Timolol inserts afforded similar decreases in intraocular pressure in open-angle glaucoma patients as did b.i.d. eyedrops, but produced lower peak timolol concentrations in plasma, 0.70 ± 0.10 ng/ml and 0.24 ± 0.05 ng/ml, respectively. After eyedrops, peak concentrations were achieved at 15.0 ± 2.2 min, while application of an insert resulted in a delayed peak (tmax = 623 ± 195 min). The insert resulted in a higher systemically absorbed fraction of the timolol dose than the eyedrop, but the peak timolol concentration and daily absorbed amount of timolol were decreased. The release rate of timolol from the inserts in vivo was only slightly less than that in vitro. Silicone devices are useful for clinical testing of controlled delivery properties of ocular drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018938310628
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Electrochemical Characterization of Human Skin by Impedance Spectroscopy: The Effect of Penetration Enhancers (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 381-385 
    Details
    ISSN: 1573-904X
    Keywords: transdermal drug delivery ; impedance spectroscopy ; human skin ; penetration enhancers ; fractal surface
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The electrochemical properties of human cadaver skin were studied in a diffusion cell with impedance spectroscopy as a function of time in the absence and presence of penetration enhancers dodecyl N,N-dimethylamino acetate and Azone. An improved electrochemical model of skin is presented, and combining the novel model with modern fractal mathematics, the effect of enhancers on the surface of skin is demonstrated. The enhancers appeared to open new penetration routes and increase the ohmic resistance, capacitive properties, and fractal dimension of skin, which means a rougher or more heterogeneous surface.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018984121415
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Effect of Some Penetration Enhancers on Epithelial Membrane Lipid Domains: Evidence from Fluorescence Spectroscopy Studies (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 288-294 
    Details
    ISSN: 1573-904X
    Keywords: penetration enhancement ; fluorescence polarization ; membrane fluidity ; fluorescent probes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of the penetration enhancers Azone, oleic acid, 1-dodecanol, dodecyl N,N-dimethylaminoacetate (DDAA), and dodecyl N,N-dimethylaminoisopropionate (DDAIP) on epithelial membrane lipids was examined using human buccal cell membranes as a model for epithelial lipid bilayer. Buccal epithelial cells (BEC) were labeled with l,6-diphenyl-l,3,5-hexatriene (DPH), l-(4-(trimethylammonio)phenyl)-6-phenyl-l,3,5-hexatriene (TMA-DPH), and 8-anilino-l-naphthalene sulphonic acid (ANS) fluorophores to characterize enhancer-induced changes in the hydrophobic core, in the superficial polar head region, and on the exterior surface, respectively, with fluorescence anisotropy and fluorescence lifetimes. All the enhancers studied were found to decrease the BEC membrane lipid packing order in a concentration-dependent and time-dependent manner in the deep bilayer region, as shown by a 37–66% decrease in anisotropy. Oleic acid was also found to disrupt membrane lipids strongly in the polar head region, causing at least a 34% decrease in anisotropy values. Azone and DDAA were shown to alter molecular movement on the surface of the bilayers (24 and 19% decrease in anisotropy, respectively). The results suggest that interaction with membrane lipid domains is an important, but not the only, mode of action for the penetration enhancers studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018919811227
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    Dodecyl N,N-Dimethylamino Acetate and Azone Enhance Drug Penetration Across Human, Snake, and Rabbit Skin (1991)
    Springer
    Pharmaceutical research 8 (1991), S. 933-937 
    Details
    ISSN: 1573-904X
    Keywords: penetration enhancer ; dodecyl N,N-dimethylamino acetate ; Azone ; percutaneous permeability ; animal models
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effectiveness of the penetration enhancers, dodecyl N, N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit ≫ human 〉 or 〈 snake.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015824100788
    Location Call Number Expected Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...