Antineoplastic Effects of N6-(△2-Isopentenyl)adenosine against L-1210 Mouse Lymphocytic Leukemic Cells Using a Polymeric Delivery System

• Published in: Journal of pharmaceutical sciences 1982-03, Vol.71 (3), p.328-331
• Main Authors: Chang, Yunik, Hacker, Bruce
• Format: Article
• Language: English
• Subjects: Adenosine - analogs & derivatives; Animals; Antineoplastic Agents; Cells, Cultured; Chromatography, High Pressure Liquid; Delivery systems-impregnated silicone polymer; Delivery systems—impregnated silicone polymer, N6-(△2-isopentenyl)adenosine; Delivery systems—impregnated silicone polymer, N6‐(Δ2‐isopentenyl)adenosine; improved delivery using impregnated silicone polymer; Isopentenyladenosine - administration & dosage; Isopentenyladenosine - analysis; Isopentenyladenosine - pharmacology; Leukemia L1210 - drug therapy; Mice; N6-(Δ2-isopentenyl)adenosine; N6-(Δ2-Isopentenyl)adenosine-antineoplastic; N6-(△2-Iso-pentenyl)adenosine—antineoplastic, improved delivery using impregnated silicone polymer; N6‐(Δ2‐Isopentenyl)adenosine—antineoplastic, improved delivery using impregnated silicone polymer; Polymers; Release rates-impregnated silicone polymer delivery system; Release rates—impregnated silicone polymer delivery system, N6-(△2-isopentenyl)adenosine; Release rates—impregnated silicone polymer delivery system, N6‐(Δ2‐isopentenyl)adenosine
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600710317

N6-(△2-Isopentenyl)adenosine (I), a nucleoside previously shown to be cytotoxic against several types of tumor cells, was impregnated in silicone polymer monolithic disc devices for release in vitro against lymphocytic mouse leukemia cells. Plotting the cumulative amount of N6-(△2-isopentenyl)adenosine released per unit area of the device versus the square root of time revealed a linear relationship. However, the higher loading dose tended to rapidly release any drug deposited on the polymer surface. The optimum loading dose of the device for the most effective antileukemic activity in 24 hr was calculated based on a plot of the release rate versus the square root of an initial loading dose. The silicone polymer-I delivery system enabled a sustained and controllable release of additional agent. It was thus possible to achieve virtually total inhibition of leukemic cell replication using the polymeric delivery system. Increased concentrations of I, without the use of the polymeric system, resulted in maximum 24 hr inhibition of only ~81%, followed by a decline in overall antileukemic activity. It is possible to achieve a more predictable release rate of N6-(△2-isopentenyl)aden-osine and corresponding antileukemic activity using a polymeric delivery system against L-1210 mouse leukemic cells in vitro. The relative data indicate the ED50 concentrations to be considerably less using the polymeric delivery system.