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Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Cisplatin/hydrogel complex in cancer therapy.
Mario Casolaro1, Renzo Cini, Barbara Del Bello
1Dipartimento di Scienze e Tecnologie Chimiche e dei Biosistemi, Medicina Sperimentale e Sanita Pubblica, Universita degli Studi di Siena, Via Aldo Moro 2, I-53100 Siena, Italy. casolaro@unisi.it
Biomacromolecules
|March 4, 2009
Summary
Amino acid hydrogels complexed with cisplatin, showing controlled release. The poly(N-acryloyl-L-phenylalanine) hydrogel released more drug, with varying cytotoxic effects depending on loading solvent.
Area of Science:
- Polymer Chemistry
- Drug Delivery Systems
- Materials Science
Background:
- Hydrogels offer potential for controlled release of chemotherapeutic agents.
- Cisplatin is a widely used platinum-based chemotherapy drug.
- Alpha-amino acid residues can be incorporated into hydrogels to modify drug complexation and release.
Purpose of the Study:
- To investigate the complexation and release of cisplatin using hydrogels functionalized with alpha-amino acid residues.
- To evaluate the impact of hydrogel composition and loading solvent on cisplatin release kinetics and drug activity.
- To assess the cytotoxic effect of released platinum species on a human melanoma cell line.
Main Methods:
- Synthesis of poly(N-acryloyl-L-phenylalanine) (P9) and poly(N-acryloyl-L-phenylalanine-co-N-isopropylacrylamide) (CP2) hydrogels.
- Complexation of cisplatin with hydrogels using water and water/DMSO mixtures as loading solvents.
- In vitro release studies in phosphate buffer solution over seven days.
- Viscometric analysis to determine the stoichiometric molar ratio of Pt(II)/L.
- Cytotoxicity assays using Me665/2/21 human melanoma cell line.
Main Results:
- Hydrogels containing L-phenylalanine and L-histidine residues successfully complexed cisplatin.
- A near zero-order release profile was observed after an initial burst effect over seven days.
- The P9 hydrogel released three times more cisplatin when loaded from a water/DMSO mixture compared to water.
- Viscometric data indicated a Pt(II)/L stoichiometric molar ratio of 0.5 in the soluble polymer analogue.
- Platinum species released from water-loaded hydrogels retained cytotoxic activity, while those from water/DMSO-loaded hydrogels did not.
Conclusions:
- The P9 hydrogel demonstrates effective complexation and controlled release of cisplatin.
- The loading solvent significantly influences the amount of cisplatin loaded and the subsequent release profile.
- The cytotoxic activity of released platinum species is dependent on the loading solvent, suggesting potential modifications during the loading process.
