Adriamycin loading and release characteristics of albumin-heparin conjugate microspheres

Cremers, H.F.M.; Verrijk, R.; Noteborn, H.P.J.M.; Kwon, Glen S.; Bae, You Han; Kim, Sung Wan; Feijén, Jan

doi:10.1016/0168-3659(94)90130-9

Cited by 15 publications

(16 citation statements)

References 23 publications

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“…It is also possible, however, that the electrostatic bond of the drug with the matrix is stabilized by self-association of ADR. This phenomenon was also observed in soluble heparin-ADR complexes [ 38 ] and a possible cause of incomplete ADR release from AHCMS [ 11 ].…”

Section: Preparation and Adriamycin Loading And Release Properties Ofmentioning

confidence: 79%

“…AHCMS could be loaded up to a payload of 34% [ 11 ], whereas the SPLMS could be loaded up to a payload of 60%. AHCMS release approximately 30% of the ADR in non-ionic medium [11], while 0% of ADR was released from SPLMS. Both types of microspheres released 80-90% of the drug in physiological salt solution.…”

Section: Preparation and Adriamycin Loading And Release Properties Ofmentioning

confidence: 99%

“…If biodegradable, biocompatible ion-exchange microspheres are used, however, this may not be a problem anymore. Recently ion-exchange albumin-heparin conjugate microspheres (AHCMS) were developed, which were shown to be biodegradable and biocompatible and which could be loaded with ADR up to payloads of 34% [10][11][12][13]. The AHCMS are prepared from a soluble conjugate of albumin and heparin.…”

Section: Introductionmentioning

confidence: 99%

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Biodegradable ion-exchange microspheres based on modified polylysines

Cremers

Lens

Seymour

et al. 1995

Journal of Controlled Release

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Poly-L-lysine was synthesized via a triethylamine initiated ring-opening polymerization of Z-L-lysine-N'~-carboxyanhydride, followed by deprotection of the E-amino group. Subsequently the polylysine was sulfamated using a pyridinium-sulfate complex to obtain polymers with varying degrees of sulfamation ranging from 0 to 100%. Cytotoxicity of these materials was tested using tetrazolium metabolism (MTI') assays with B16F10 and P388 cell lines. Cytotoxicity of sulfamated polylysines with a degree of sulfamation of 80% and higher was significantly reduced as compared with the native polylysines. In both cell lines, LDso of the sulfamated materials was higher than 5 mg/ml, which was the highest dose tested. LDso of the native polylysines was lower than 0.1 mg/ml in the case of B16F10 and lower than 0.01 mg/ml in the case of P388 cells. Sulfamated polylysines with a degree of sulfamation of 80% were used to prepare microspheres (SPLMS). The microspheres were stabilized using glutaraldehyde or oxidized dextran as a crosslinking agent. The swelling ratio (defined as V~wollen/Vdr~ed) of the SPLMS in aqueous media decreased with increasing ionic strength and crosslink density. The pH (ranging from 3 to 11) had no influence on the swelling ratio of SPLMS. The maximal swelling ratio was approximately 35 (SPLMS crosslinked with 0.5% glutaraldehyde in distilled water). SPLMS could be loaded with adriamycin up to a payload of 60%, which was not influenced by the crosslinking method. The adriamycin release was controlled by the ionic strength of the release medium: no drug was released in non-ionic medium such as distilled water, while 80% of the drug was released in phosphate buffered saline. This effect of the change in ionic strength could be applied to prepare a microsphere suspension in non-ionic medium such as 5% glucose solution, which does not contain free adriamycin. The drug would only be release after intra-arterial administration of this suspension, due to the presence of the blood.

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Section: Preparation and Adriamycin Loading And Release Properties Ofmentioning

confidence: 79%

Section: Preparation and Adriamycin Loading And Release Properties Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Biodegradable ion-exchange microspheres based on modified polylysines

Cremers

Lens

Seymour

et al. 1995

Journal of Controlled Release

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“…Adriamycin • HC1 was a kind gift from Pharmachemie, Haarlem, The Netherlands. Adriamycin-loaded microspheres (ADR-AHCMS) were obtained by loading AHCMS with ADR up to a payload of 25.4% w/w as described previously (Cremers et al, 1994c).…”

Section: Methodsmentioning

confidence: 99%

“…ADR concentrations of the blood samples and the tissue extracts were determined using HPLC according to a standard procedure that was described previously (Cremers et al, 1994c). ADR tissue levels were calculated from the calibration curve using the log ratio of the peak heights of ADR and IS.…”

Section: Hplc Analysis Of Adr Samplesmentioning

confidence: 99%

Improved distribution and reduced toxicity of adriamycin bound to albumin-heparin microspheres

Cremers

Verrijk

Bayon

et al. 1995

International Journal of Pharmaceutics

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Adriamycin (ADR) was formulated in albumin-heparin conjugate microspheres (AHCMS) to improve site-specific delivery and to reduce the toxicity of the drug. The effect of formulating ADR in AHCMS was investigated upon intrahepatic administration to male Wag/Rij rats. After intraveno-portal (i.v.p.) administration of ADR-AHCMS, ADR peak plasma concentrations were reduced 10-fold and ADR tissue levels of non-target tissues were significantly reduced, as compared to i.v.p, administration of the free drug. At an i.v.p, administered drug dose of 7.5 mg/kg, free ADR showed distinct signs of acute toxicity. At the same dose of ADR-AHCMS, signs of toxicity were absent. Cardiac function parameters which were determined using an isolated working heart model did not change as a result of i.v.p, administration of free ADR or ADR-AHCMS at a dose of 7.5 mg/kg. Heart weights of animals in the ADR-AHCMS or the free ADR groups, however, were significantly lower than controls. Dose tolerance studies after intrahepatic-arterial (i.h.a.) administration of free ADR, empty AHCMS and ADR-AHCMS in rats demonstrated that empty AHCMS are tolerated at a dose of 45 mg/kg. Free ADR was tolerated at a dose of 4 mg/kg, whereas ADR-AHCMS were tolerated up to a dose of 10 mg ADR/kg, as indicated by the survival.

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