Dataset Information

Polylactide conjugates of camptothecin with different drug release abilities.

ABSTRACT: Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems-important delivery systems for anti-cancer agents.

SUBMITTER: Oledzka E

PROVIDER: S-EPMC6270997 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Polylactide conjugates of camptothecin with different drug release abilities.

Oledzka Ewa E Horeglad Paweł P Gruszczyńska Zuzanna Z Plichta Andrzej A Nałęcz-Jawecki Grzegorz G Sobczak Marcin M

Molecules (Basel, Switzerland) 20141125 12

Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled desi ...[more]

PMID: 25429566

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Project description:N-Acetyl-L-cysteine (NAC) is an antioxidant and anti-inflammatory agent with significant potential in clinical applications including stroke and neuroinflammation. The drug shows high plasma binding upon IV administration, requiring high doses and associated side effects. Through the use of an appropriate delivery vehicle, the stability and efficacy of NAC can be significantly improved. Dendrimers are an emerging class of nanoscale drug delivery vehicles, which enable high drug payloads and intracellular delivery. Poly(amidoamine) (PAMAM) dendrimer-NAC conjugates having cleavable disulfide linkages are designed for intracellular delivery based on glutathione levels. We have successfully synthesized two conjugates with a cationic G4-NH(2) and an anionic G3.5-COOH PAMAM dendrimer with NAC payloads of 16 and 18 per dendrimer, respectively, as confirmed by (1)H NMR and MALDI-TOF analysis. NAC release from the conjugates at intracellular and extracellular glutathione (GSH) concentrations were evaluated by reverse phase HPLC (RP-HPLC) analysis, and approximately 70% of NAC payload was released within one hour at intracellular GSH concentrations (approximately 10 mM), whereas negligible NAC release was observed at extracellular GSH levels (2 microM). FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells (the target cells in vivo). The significantly improved efficacies of dendrimer-NAC conjugates in activated microglial cells was confirmed by measuring the nitrite inhibition in the cell culture medium, which is an indication of the antioxidative property of the drug. Both G4-NH(2) and G3.5-COOH conjugates showed significantly better nitrite inhibition both at 24 and 72 h compared to free NAC, by as much as a factor of 16. The results indicate that PAMAM dendrimer conjugates produce higher local NAC concentration inside the cells, with GSH-sensitive disulfide linker enabling efficient and rapid cellular release of the drug.

Dataset Information

Polylactide conjugates of camptothecin with different drug release abilities.

Publications

Polylactide conjugates of camptothecin with different drug release abilities.

Similar Datasets

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