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1

Kinetics of a nucleoside release from lactide-caprolactone and lactide-glycolide polymers in vitro.

100%

Kryczka T., Grieb P., Bero M., Kasperczyk J., Dobrzynski P.

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2000

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vol. 47

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issue 1

59-64

EN

We assessed the rate of release of a model nucleoside (adenosine, 5%, w/w) from nine different lactide-glycolide or lactide-caprolactone polymers. The polymer discs were eluted every second day with an artificial cerebrospinal fluid at the elution rate roughly approximating the brain extracellular fluid formation rate. Adenosine in eluate samples was assayed by HPLC. Three polymers exhibited a relatively constant release of adenosine for over four weeks, resulting in micromolar concentrations of nucleoside in the eluate. This points to the neccessity of further development of polymers of this types as intracerebral nucleoside delivery systems for local treatment of brain tumors.

2

5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.

100%

Grieb P., Kryczka T., Wójtowicz R., Kawiak J., Kazimierczuk Z.

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2002

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vol. 49

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issue 1

129-137

EN

Phenylacetic and retinoic acids are carboxyacidic cell differentiating agents displaying anticancer activities. We report on a new class of compounds including the 5'-esters of 2'-deoxyadenosine (dA) or 2-chloro-2'-deoxyadenosine (cladribine, 2CdA) and the aforementioned acids. The rationale behind the synthesis of these esters was that if they are hydrolyzed inside the lymphoid cells, either dA will be removed from the intracellular environment by deamination, or 2CdA will be phosphorylated and accumulated. In either case targetted delivery of the differentiating agent to the lymphoid cells may be envisaged. The said compounds were synthesized by the Mitsunobu procedure employing triphenylphosphine and azadicarboxylic acid esters, and their stability was tested against various esterases. Esters of dA and 2CdA with phenylacetic acids were found to be resistant to enzymatic hydrolysis, whereas those with retinoic acids were efficiently hydrolyzed by commercially available hepatic esterase as well as by esterases present in the blood plasma and in diluted human lymphocyte lysate. Susceptibility to enzymatic hydrolysis was found to be a prerequisite of cytotoxic and/or differentiating activity of these esters in leukemic cell lines.

3

In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.

86%

Kryczka T., Bero M., Kasperczyk J., Dobrzyński P., Marciniec B., Popierzal-Brzezińska M., Grieb P.

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2002

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vol. 49

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issue 1

205-210

EN

The aims of our study were to assess the release of cytotoxic nucleoside analogs 5-fluorouracil and 2-chloro-2'-deoxyadenosine from different lactide-glycolide or lactide-caprolactone biodegradable copolymers and the effects of sterilization on this release. The polymers were sterilized either with ethylene oxide at 37°C, or with gamma radiation (15 kGy, 20 kGy, or 25 kGy). The kinetics of nucleoside release from the copolymers were measured over 50 days. Four copolymers exhibited relatively constant release of nucleosides in micromolar concentrations during the entire observation period. Sterilization with either ethylene oxide or gamma radiation only slightly influenced nucleoside release. Further development of these copolymers as an intracerebral nucleoside delivery system for local treatment of brain tumors is indicated.

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3 Acta Biochimica Polonica

2 2002

1 2000

3 Grieb P.

3 Kryczka T.

2 Bero M.

2 Kasperczyk J.

1 Dobrzynski P.

1 Dobrzyński P.

1 Kawiak J.

1 Kazimierczuk Z.

1 Marciniec B.

1 Popierzal-Brzezińska M.

1 Wójtowicz R.

Kinetics of a nucleoside release from lactide-caprolactone and lactide-glycolide polymers in vitro.

5'-Esters of 2'-deoxyadenosine and 2-chloro-2'-deoxyadenosine with cell differentiation-provoking agents.

In vitro release of cytotoxic nucleoside analogs from lactide-caprolactone and lactide-glycolide copolymers.