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Sharma, Uma S.; Sharma, Amarnath; Chau, Robert I.; Straubinger, Robert M.

doi:10.1023/a:1012136925030

Cited by 68 publications

(30 citation statements)

References 23 publications

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“…The particle attachmeni method (40), the equation of btate method (41), as well as the u& of modern 'acid-base approach' (10,19) have all shown the normal epiihelial cells with associated iiycocalix to be almost as hydrophilic and as wettable by the aquedljs media as the corneal mucus. Nor is this conclusion surprising, because, like any number of cells with an ekracellular coat of glycosylated glycocalyx (16.17, 20-22), the corneal epithelial &lls (18,19) …”

Section: Sharmamentioning

confidence: 99%

Acid-Base Interactions in the Cornea-Tear Film System: Surface Chemistry of Corneal Wetting, Cleaning, Lubrication, Hydration and Defense

Sharma

1998

Journal of Dispersion Science and Technology

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Various surfacechemical interactions among the corneal epithelium, ocular mucous gel, tear film and tear film contaminants (e.g., cellular debris, lipids, bacteria) are characterized based on their apolar and polar (acid-base) surface properties. Based on this approach, the surfacechemical pathways of the tear film breakup and of the corneal epithelial lubrication, cleansing, wetting and defense are proposed. A strong monopolar repulsion keeps mucus in the form of a highly hydrated gel. which cannot adhere to the normal glycocalix carrying epithelial surface. but forms an effective surfacechemical trap for the apolar and weakly polar hydrophobic contaminants. However, mucusdeficiency andlor a host of epithelial surface abnormalities (e.g., increased cell loss, chemical or morphologic changes, damage) can initiate a vicious cycle comprising of factors such as: increased mucus contamination, loss of mucus and epithelial hydrophilicity, abnormal adhesion and aggregation of mucus. reduced mucus mobility and faulty surface cleansing. All of these faclors can conspire to produce a chronically unstable tear film secondary to the loss of corneal surface wettability. Copyright0 1998 by Marscl Dskkcr, Ine.Downloaded by [New York University] at 00:55 01 August 2015 SHARMAThe major objective of this paper is to e!xplore the surface-chemical mechanisms re:;ponsible for the maintenance of the corneal wetting by the tear film in rlormal eyes, and for a rapid breakup of the tear film seen in association with a variety of dry eye syndromes (1,2). A holistic understanding c)f the sequence of events leading to the tear film1 breakup has remained elusive even after three decades of intense activity in this area. What appears certain is that the tear breakup is secondary to the nonwettability of the c.orneal surface, which is nearly a tautological statement. Indeed, numerous experimental (3-7) and theoretical (4-9) studies have conclusively demonstrated that even relatively thick (-100 pm) liquid films on norwettable substrates can dewet spontaneously by the nucleation and growth of initial defects or dry spots.In the context of tear film breakup, however, there are several unanswered questions. What factors are responsible for maintaining the corneal surface wettability in health'? More importantly, what triggers its nonwettability by the aqueous tears in a variety of ocular surface and tear film disorders? As will be argued in this paper, the answers are not likely to be straightforward in that they involve subtle interplays of-surfacechemical and physiological factors. To address these questions in a meaningful way, a proper understanding of both the apolar and the polar (acid-base) surface properties of th~e corneal epithelium and mucus is required. While the early approaches (1 0-12) based on Zisman's method of critical surfacle tension (13) did produce some limited insights, it is now generally agreed that this method lacks the requisite framework to address the problem 04 polar interactions in aqueous media. Further progress ...

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Section: Sharmamentioning

confidence: 99%

Acid-Base Interactions in the Cornea-Tear Film System: Surface Chemistry of Corneal Wetting, Cleaning, Lubrication, Hydration and Defense

Sharma

1998

Journal of Dispersion Science and Technology

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“…In Trials 3 and 4, mice were injected intracranially with rat C6 glioma cells and treated with the p97-ADR conjugates SYN002 and SYN018 either via tail vein injection (Trial 3) or via intra-jugular injections (Trial 4). These brain tumours grew slower than ZR-75-1 tumours resulting in an average survival time of 21 days for untreated animals, which is typical for these tumours [12,31]. In both trials, again significant increases in mean and median survival were achieved.…”

Section: Discussionmentioning

confidence: 91%

Development of a potential protein vector (NeuroTrans) to deliver drugs across the blood–brain barrier

Gabathuler

Arthur

Kennard

et al. 2005

International Congress Series

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“…For DXR and other anthracyclines incorporated in long-circulating liposomes, effects that differ from the unencapsulated drug have been observed [12][13][14][15]33,36]. Carrier-mediated alterations in drug biodistribution, bioavailability, and tissue-specific metabolism may underlie these overall changes in pharmacology.…”

Section: Discussionmentioning

confidence: 99%

“…Small, unilamellar, sterically stabilized Doxorubicin liposomes (SSL-DXR) were prepared from DSPC:Chol:PEG-DSPE in a 9:5:1 mole ratio utilizing a remote loading procedure [15,16,32] that was driven by combined ammonium sulfate and pH gradients, as previously described [33]. Unencapsulated drug was removed by dialysis.…”

Section: Preparation Of Doxorubicin Liposomesmentioning

confidence: 99%

“…Rat 9L gliosarcoma brain tumor cells (4 × 10 4 cells) were implanted stereotaxically in the caudate/putamen brain region of Fisher 344 male rats as described previously [33]. All animals were housed, cared for, and used following a SSL-DXR was administered at 5.67 mg/kg by tail vein injection 7 days after tumor implantation.…”

Section: Brain Tumor Implantation Treatment and Samplingmentioning

confidence: 99%

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Quantification of Doxorubicin and metabolites in rat plasma and small volume tissue samples by liquid chromatography/electrospray tandem mass spectroscopy

Arnold

2004

Journal of Chromatography B

112

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The anthracycline Doxorubicin (DXR) is used widely for the treatment of human malignancies, and drug delivery technologies are under investigation to enhance antitumor selectivity and effectiveness. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to identify and quantify DXR and key metabolites in small-volume biological samples. The assay was linear over the therapeutically relevant concentration range (0.125-10,000 nM); in brain tissue, the lower limit of quantification was 0.247 nM and the sensitivity was 1.4 pg. The ability to quantify DXR and detect metabolite formation may provide insight into the toxicity and bioavailability of drug incorporated into carriers such as liposomes.

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Abstract: Liposomes can be used to enhance delivery of drugs to brain tumors and increase therapeutic effect. The therapeutic effect may arise from release of drug from liposomes extravasated in discrete regions of the tumor vasculature and the extravascular space.

Cited by 68 publications

References 23 publications

Acid-Base Interactions in the Cornea-Tear Film System: Surface Chemistry of Corneal Wetting, Cleaning, Lubrication, Hydration and Defense

Acid-Base Interactions in the Cornea-Tear Film System: Surface Chemistry of Corneal Wetting, Cleaning, Lubrication, Hydration and Defense

Development of a potential protein vector (NeuroTrans) to deliver drugs across the blood–brain barrier

Quantification of Doxorubicin and metabolites in rat plasma and small volume tissue samples by liquid chromatography/electrospray tandem mass spectroscopy

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