Acidic pH-stimulated tiotropium release from porous poly(lactic-co-glycolic acid) microparticles containing 3-diethylaminopropyl-conjugated hyaluronate

In this study, we developed porous poly(lactide-co-glycolide) (PLGA) microparticles (PM) exhibiting pH-activated drug release properties. The PMs were prepared via the water-in-oil-in-water (W₁/O/W₂) multi-emulsion method using PLGA, 3-diethylaminopropyl amine (DEAP)-conjugated hyaluronate (HA) (HA-DEAP), and an anti-cholinergic model drug (tiotropium). Here, HA-DEAP was incorporated into the PMs; it acted as a drug release activator, accelerating drug release. In vitro drug release studies revealed that the tiotropium was released from the PMs as their pores were destabilized by eletrostatic interactions between the carboxyl groups (negatively charged) of the HA molecules and the tertiary amine groups (positively charged) of the DEAP moieties under acidic environments. This PLGA microparticle system, which contains a HA-DEAP, could provide unique advantages in treating chronic obstructive pulmonary disease (COPD) with chronic respiratory acidosis.[Figure not available: see fulltext.]