Carolyn A Converse

Publications (4)7 Total impact

• Article: Tumour gene expression from C12 spermine amphiphile gene delivery systems.

  Pei Lee Kan, Alexander I Gray, Laurence Tetley, Carolyn A Converse, Andreas G Schätzlein, Ijeoma F Uchegbu
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  ABSTRACT: Gene therapy requires safe and efficient gene delivery systems. Towards this aim both the gene formulation and tumour transfection ability of C12 spermine amphiphiles were tested. Five amphiphiles were synthesised and characterised: 1-[N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G0--a C12 spermine amphiphile), a poly(ethylene glycol) (PEG, MW = 2 kDa) derivative of 12G0, 1,12-[N,N-bis(3-aminopropyl)-1,4-butane diamine] dodecane (12G1--a C12 spermine bolaamphiphile) and N-methyl quaternary ammonium derivatives of both 12G0 (12QG0) and 12G1 (12QG1). All amphiphiles except 12G0, which precipitates, yield nanoparticles in aqueous media with and without DNA. Thus when 12G0 is substituted with either quaternary ammonium or PEG groups it forms nanoparticles both with and without DNA. The minimum nitrogen, phosphate ratio required to completely condense DNA (NP) was inversely proportional to the particles' zeta potential (zeta), NP = 1626/zeta(0.98). Biological testing showed that both PEG and quaternary ammonium groups diminished the membrane lytic ability of these C12 amphiphiles. On intratumoural injection, while PEG groups hamper gene transfer, the quaternary ammonium amphiphile (12QG0) produces tumour confined gene expression that is 80% of that produced by linear poly(ethylenimine) (LPEI, MW = 22 kDa); while the intratumoural injection of LPEI produced significant gene expression in the liver and lung, making 12QG0 suitable for the administration of cytotoxic tumouricidal genes.
  Journal of Drug Targeting 08/2005; 13(6):345-57. · 2.70 Impact Factor
• Article: Comparison between oleic acid and docosahexaenoic acid binding to interphotoreceptor retinoid-binding protein.

  Ekaterina M Semenova, Carolyn A Converse
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  ABSTRACT: Interphotoreceptor retinoid-binding protein (IRBP), which binds retinoids and fatty acids, is the major soluble protein in the interphotoreceptor matrix (IPM) but its role remains ambiguous. Using competitive fluorescence and tryptophan-quenching assays we found oleic acid and other cis-monounsaturated fatty acids bind much more strongly than does docosahexaenoic acid to bovine IRBP. IPM's fatty acid composition was determined: it was richer in oleic acid than either the retinal pigment epithelium or rod outer segments. This may imply oleic acid has a key role in the balance and transport of retinoids and fatty acids in the retina.
  Vision Research 01/2004; 43(28):3063-7. · 2.41 Impact Factor
• Article: Stabilization of All-trans-retinol by Cyclodextrins: A Comparative Study Using HPLC and Fluorescence Spectroscopy

  Ekaterina M. Semenova, Alan Cooper, Clive G. Wilson, Carolyn A. Converse
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  ABSTRACT: Purpose: To formulate preparations incorporating cyclodextrins (CDs) which could be used for direct delivery to the retina of vitamin A (all-trans-retinol), while also protecting it from degradation in the aqueous environment. Vitamin A supplementation is being considered for treatment of several ophthalmic diseases characterised by progressive photoreceptor degeneration. Methods: The complexation between vitamin A and ten cyclodextrins, Captisol(sulfobutyl ether-7--cyclodextrin), hydroxypropyl--CD, 2-hydroxypropyl--CD, -CD, hydroxypropyl--CD, hydroxypropyl--CD, -CD, methyl--CD,Heptakis-(2,6-di-O-methyl)--CD andHeptakis-(2,3,6-tri-O-methyl)--CD,was investigated using bothhigh sensitivity fluorescence spectrometry and HPLC (high pressure liquid chromatography). Samples of retinol-CD complexes in phosphate buffer, pH 7.4 were analysed for up to 72 hours. Optimum conditions for formation of the Captisol-retinol complexes were investigated. Results: Using spectroscopic measurements and HPLC, the complexes formed between ten cyclodextrins and all-trans-retinol were evaluated. The results indicate that all cyclodextrins tested were able to form inclusion complexes as shown by the fluorescence signals which are considerably larger than those obtained in the absence of cyclodextrin. Only minimal degradation of retinol over 48 hours was observed with three of these cyclodextrins. Captisol was able to stabilise all-trans-retinol for up to 72 hours, as shown by HPLC, and the optimum ratio of Captisol to retinol was determined to be 50 to 1. Addition of glutathione and decrease in pH did not improve stability of the complex. Conclusions: This survey suggests that Captisol and other cyclodextrins could be used to stabilise and solubilise vitamin A in aqueous media and this establishes the basis for an ocular Captisol-retinol drug delivery system now under development in our laboratory.
  Journal of Inclusion Phenomena 11/2002; 44(1):155-158. · 1.89 Impact Factor
• Article: Energetics of primary processes in visual excitation: photocalorimetry of rhodopsin in rod outer segment membranes

  Alan Cooper, Carolyn A. Converse
  04/2002;