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  • 1
    Electronic Resource
    Electronic Resource
    Biodistribution of Micelle-Forming Polymer–Drug Conjugates (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 970-974 
    Details
    ISSN: 1573-904X
    Keywords: polymeric micelles ; drug delivery systems ; cancer therapy ; Adriamycin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Polymeric micelles have potential utility as drug carriers. To this end, polymeric micelles based on AB block copolymers of polyethylene oxide (PEG) and poly(aspartic acid) [p(Asp)] with covalently bound Adriamycin (ADR) were prepared. The micelle forming polymer–drug conjugates [PEO-p(Asp(ADR)] were radiolabeled and their biodistribution was investigated after intravenous injection in mice. Long circulation times in blood for some compositions of PEO-p[Asp(ADR)] conjugates were evident, which are usually atypical of colloidal drug carriers. This was attributed to the low interaction of the PEO corona region of the micelles with biocomponents (e.g., proteins, cells). Low uptake of the PEO-p(Asp(ADR)] conjugates in the liver and spleen was determined. The biodistribution of the PEO-p[Asp(ADR)] conjugates was apparently dependent on micelle stability; stable micelles could maintain circulation in blood, while unstable micelles readily formed free polymer chains which rapidly underwent renal excretion. Long circulation times in blood of PEO-p(Asp(ADR)] conjugates are thought to be prerequisite for enhanced uptake at target sites (e.g., tumors).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018998203127
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  • 2
    Electronic Resource
    Electronic Resource
    Physical Entrapment of Adriamycin in AB Block Copolymer Micelles (1995)
    Springer
    Pharmaceutical research 12 (1995), S. 192-195 
    Details
    ISSN: 1573-904X
    Keywords: Adriamycin ; polymeric micelles ; AB block copolymer ; drug delivery systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The entrapment of Adriamycin (ADR) in micelles composed of AB block copolymers (poly(ethylene oxide-co-β-benzyl L-aspartate) (PEO-PBLA)) was investigated. The loading process involved transfer of ADR and PEO-PBLA into an aqueous milieu from dimethyl-formamide (DMF) through a dialysis procedure. Evidence for the physical entrapment of ADR in the polymeric micelles was derived from fluorescence spectroscopy and gel permeation chromatography (GPC). The total fluorescence intensity of ADR was low, suggesting that the drug was self-associated in the micelles. In addition, quenching experiments, using a water-soluble quencher (iodide (I–)), showed that the fluorescence of ADR present in micellar solutions was largely unaffected by I–, whereas the fluorescence of free ADR was readily quenched. From Stern-Volmer plots, quenching constants (KSV) of 2.2 and 17 M−l were determined for ADR in micellar solutions and free ADR, respectively. As a result of the entrapment of ADR in the micelles, ADR binds only slightly serum albumin as evidenced by GPC. In contrast, ADR readily binds serum albumin in aqueous solutions. The findings suggest that ADR is stably entrapped in PEO-PBLA micelles. ADR entrapment in polymeric micelles is expected to affect markedly the pharmacokinetics of ADR.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1016266523505
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Glucose-Responsive Gel from Phenylborate Polymer and Poly (Vinyl Alcohol): Prompt Response at Physiological pH Through the Interaction of Borate with Amino Group in the Gel (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 289-293 
    Details
    ISSN: 1573-904X
    Keywords: boronic acid ; poly(vinyl alcohol) ; amino group ; glucose gel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To design glucose-responsive gels based on the complexation between polymers having phenylboronic acid groups and poly (vinyl alcohol). Specifically, high-glucose sensitivity at physiological pH was achieved through the interaction of phenylborate with amino groups. Method. Terpolymers of m-acrylamidophenylboronic acid, N,N-dimethylaminopropylacrylamide (DMA-PAA), and N,N-dimethylacrylamide were prepared. DMAPAA was introduced in the terpolymer to stabilize phenylborate-polyol complex at physiological pH. The effect of amino groups on complex stabilization was estimated from viscosity as well as UV spectrum measurements. Results. A good correlation was observed between complexation rate and fraction of phenylborate as well as DMAPAA in the terpolymers. In line with this increased complexation rate. UV difference spectra measurement revealed that ionization of phenylboronic acid was facilitated in the terpolymer due to the interaction with DMAPAA. Further, sensitive change in the complexation rate was demonstrated with a variation in glucose concentration, which is in sharp contrast with the poor glucose-sensitivity of the polymer without DMAPAA. Conclusions. The introduction of an amino group into phenylborate polymers was quite effective for increasing the complexation ability and the glucose responsivity at physiological pH. These results suggest the feasibility of this complex-gel system in designing a self-regulated insulin-releasing device.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012033718302
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    Paper (German National Licenses)
    Fulltext
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