Thermoresponsive polymer membrane for the local delivery of drugs

Abstract

OBJECTIVE: To develop a temperature-responsive polymer membrane that is permeable to drug only at temperatures above 42oC. A triggerable implant that releases drug only when heated can be made by encapsulating a drug reservoir with such a thermoresponsive membrane. Such an implant can be applied in clinical situations in which it is desirable to release drug only on demand, such as erectile dysfunction. METHODS: A porous polyethylene (PE) membrane was modified by fillings its pores with either docosane or a docosane:eicosane mixture. The melting transition of the alkanes corresponds to a diffusional switch, thus, the alkane melting point corresponds to the membrane release trigger temperature. The onset of melting for each alkane and the alkane mixture was measured by differential scanning calorimetry. Using a diffusion cell, the permeability of propranolol hydrochloride (PRO) through the thermoresponsive membrane was measured. RESULTS: PRO permeation through the docosane-absorbed PE membrane at 37oC and 45oC was reversible, and was reproducible after five cycles of temperature oscillation. From an aqueous solution reservoir, the ratio of PRO permeability through the docosane-absorbed PE membrane at 45oC versus 37oC was 378±65. Similarly, the ratio of PRO permeability through the docosane:eicosane (90:10) PE membrane at 42.5oC and at 37oC was 235±56. CONCLUSIONS: The high on/off permeability ratio achieved with PRO provides promise for the development of a thermoresponsive implant by using this membrane and a suitable drug. Local heating of the implant may be achieved by external power sources such as ultrasonic or microwave heaters.