Poly(amidoamines) are soluble polymers containing tertiary amino and amido groups regularly arranged along the macromolecular chain, and their net average charge alters considerably as pH changes from neutral to acidic leading to a change in conformation. This property provides the possibility to design polymer-drug conjugates that are, following intravenous administration, relatively compacted and thus protect a drug payload in the circulation, but following pinocytic internalisation into acidic intracellular compartments unfold permitting pH-triggered intracellular drug delivery. To study the feasibility of this approach, a covalent conjugate of a poly(amidoamine) (MBI) was prepared to contain the membrane lytic non-ionic detergent Triton X-100 (as a model), and its ability to lyse red blood cells in vitro was used as an indicator of conjugate conformation at different pHs. Although Triton X-100 was highly lytic at pH 5.5, 7.4 and 8.0, and the parent polymer MBI was not lytic under any conditions, the conjugate only showed concentration-dependent red blood cell lysis at pH 5.5. Moreover, incubation of human leukaemic cells (CCRF) with these substrates showed conjugate to be more toxic than MBI (IC50 values of 100μg/ml and 650μg/ml respectively) and less toxic than Triton X-100 (IC50 of 1μg/ml).

A POLYMER TRITON X-100 CONJUGATE CAPABLE OF PH-DEPENDENT RED-BLOOD-CELL LYSIS - A MODEL SYSTEM ILLUSTRATING THE POSSIBILITY OF DRUG-DELIVERY WITHIN ACIDIC INTRACELLULAR COMPARTMENTS / D. R., F. P., S. D., T. A., E. Ranucci, B. F.. - In: JOURNAL OF DRUG TARGETING. - ISSN 1061-186X. - 2:4(1994), pp. 341-347.

A POLYMER TRITON X-100 CONJUGATE CAPABLE OF PH-DEPENDENT RED-BLOOD-CELL LYSIS - A MODEL SYSTEM ILLUSTRATING THE POSSIBILITY OF DRUG-DELIVERY WITHIN ACIDIC INTRACELLULAR COMPARTMENTS

E. Ranucci;
1994

Abstract

Poly(amidoamines) are soluble polymers containing tertiary amino and amido groups regularly arranged along the macromolecular chain, and their net average charge alters considerably as pH changes from neutral to acidic leading to a change in conformation. This property provides the possibility to design polymer-drug conjugates that are, following intravenous administration, relatively compacted and thus protect a drug payload in the circulation, but following pinocytic internalisation into acidic intracellular compartments unfold permitting pH-triggered intracellular drug delivery. To study the feasibility of this approach, a covalent conjugate of a poly(amidoamine) (MBI) was prepared to contain the membrane lytic non-ionic detergent Triton X-100 (as a model), and its ability to lyse red blood cells in vitro was used as an indicator of conjugate conformation at different pHs. Although Triton X-100 was highly lytic at pH 5.5, 7.4 and 8.0, and the parent polymer MBI was not lytic under any conditions, the conjugate only showed concentration-dependent red blood cell lysis at pH 5.5. Moreover, incubation of human leukaemic cells (CCRF) with these substrates showed conjugate to be more toxic than MBI (IC50 values of 100μg/ml and 650μg/ml respectively) and less toxic than Triton X-100 (IC50 of 1μg/ml).
Drug delivery; PH-Dependent delivery; Poly(amido amines); Targeting
Settore CHIM/04 - Chimica Industriale
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/188459
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