To modulate the pharmacokinetics and bio-distribution of chemotherapeutic agents is a promising strategy to improve the therapeutic efficacy minimizing the adverse reactions in cancer treatment. The use of Red Blood Cells (RBCs) as drug carriers is a challenging topic with potentially relevant clinical applications, including the prolongation of the time a drug is present in the body in its active form, and the reduction of toxicity due to a delayed release by RBCs. We demonstrated that fluid shear stress is able to temporary open the pores naturally present in RBCs membrane, allowing the diffusion of a molecule from its original solution to the RBCs cytoplasm. The novelty of the method illustrated here is the possibility to use autologous RBCs in a device properly designed to be directly connected to the patient, minimizing the handling of blood by operator. Preliminary tests were performed on human blood using a microfluidic channel with optimized dimensions. By setting the proper molecule concentration and fluid flow rate, it is possible to achieve more than 80% efficiency in the encapsulation. The presence of fluorescent probe molecules inside the cells was confirmed both by confocal microscopy and by cytofluorimetric analysis, demonstrating also that RBCs maintained their physiological shape after microfluidic solicitation. A delicate balance needs to be maintained in order to achieve adequate encapsulation in relatively short times and avoid mechanical hemolysis of the cells. Based on these promising results, the validation of the prototype is currently ongoing by performing in vitro release test on chemotherapy drugs.

Drug in a cell: an innovative device for a smarter chemotherapy

M. Piergiovanni;G. Casagrande;E. Bianchi;ML. Costantino
2019-01-01

Abstract

To modulate the pharmacokinetics and bio-distribution of chemotherapeutic agents is a promising strategy to improve the therapeutic efficacy minimizing the adverse reactions in cancer treatment. The use of Red Blood Cells (RBCs) as drug carriers is a challenging topic with potentially relevant clinical applications, including the prolongation of the time a drug is present in the body in its active form, and the reduction of toxicity due to a delayed release by RBCs. We demonstrated that fluid shear stress is able to temporary open the pores naturally present in RBCs membrane, allowing the diffusion of a molecule from its original solution to the RBCs cytoplasm. The novelty of the method illustrated here is the possibility to use autologous RBCs in a device properly designed to be directly connected to the patient, minimizing the handling of blood by operator. Preliminary tests were performed on human blood using a microfluidic channel with optimized dimensions. By setting the proper molecule concentration and fluid flow rate, it is possible to achieve more than 80% efficiency in the encapsulation. The presence of fluorescent probe molecules inside the cells was confirmed both by confocal microscopy and by cytofluorimetric analysis, demonstrating also that RBCs maintained their physiological shape after microfluidic solicitation. A delicate balance needs to be maintained in order to achieve adequate encapsulation in relatively short times and avoid mechanical hemolysis of the cells. Based on these promising results, the validation of the prototype is currently ongoing by performing in vitro release test on chemotherapy drugs.
2019
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Descrizione: Poster Humanitas Research Day 2019
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/1121007
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