Stimuli-responsive Polymers for Pulsatile Release

In this study, stimuli-responsive polymers have been utilized for generating pulsatile drug release systems. Pulse-release is more common in multi-unit systems, in which a programmable lag time between different dose/drug is essential. The lag time varies from hours to months depending on the disease state and drug types. The burst release after a certain lag time in the pulsatile system is commonly achieved by one of these approaches: rupturing (swelling/ osmotic pressure), degradation (hydrolysis/ enzyme), and changed permeability of the coating membrane. In this study, the release time of the implant is controlled by the thickness of the encapsulation layer, which consists of 5 % wt solution of gelatin, 1.5 % wt of sucrose, 1.5 % wt of glycerol, and 0.5 % wt of Poly(vinyl alcohol) (PVA) in DI water, dried at ambient condition for 24 hr. The lag time was controlled by a coating layer on the encapsulation. Samples designed to have 4-6 days lag time, were prepared by soaking the encapsulation in 0.5% glutaraldehyde (GA) aqueous solutions for 10 min to crosslink, and then soaked into a 20 % wt poly(lactic acid)(PLA) in methylene chloride 3 times, 30 sec each. Samples designed to have a 20-40 hr lag time were only soaked in PLA one time for 30 sec. The PLA-coated encapsulant was then put into 5 mL PBS buffer to test the drug release profile. PBS was replaced every 2 hr for samples for hour-range lag time, and 12 hr for day-range lag time. UV-vis spectroscopy was performed to characterize the release behavior.