Drug-Induced Phase Separation in Polyelectrolyte Microgels

Area of Science:

• Materials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Polyelectrolyte microgels are crucial in drug delivery, undergoing volume phase transitions upon interaction with amphiphilic molecules.
• These transitions typically involve a complete swelling or collapse, studied in large solution volumes.
• The formation of distinct core-shell structures during these transitions has been observed.

Purpose of the Study:

• To investigate the hypothesis that thermodynamic factors stabilize the boundary between collapsed and swollen phases within microgels, allowing coexistence at equilibrium.
• To study the interaction between sodium polyacrylate (PA) microgels and amitriptyline hydrochloride (AMT) at varying ionic strengths.

Main Methods:

• Utilized a specialized microscopy cell and micromanipulators to observe single microgels in small liquid volumes of AMT solution.
• Employed rhodamine B as a fluorescent probe to map AMT micelle distribution.
• Determined AMT content using spectrophotometry and studied AMT binding and distribution in suspensions.

Main Results:

• Observed coexistence of collapsed, AMT-rich, and swollen, AMT-lean phases in equilibrium or as metastable states at intermediate AMT loading.
• At 10 mM ionic strength, collapsed phases formed non-core-shell structures (domains or calottes).
• At 155 mM ionic strength, initially collapsed microgels showed a swollen shell and collapsed core after partial AMT release; suspensions exhibited bimodal distributions.

Conclusions:

• The results support the hypothesis that thermodynamic factors stabilize the boundary between collapsed and swollen phases within the same microgel.
• This coexistence phenomenon offers new insights into the behavior of microgels in drug delivery applications.
• The findings highlight the importance of considering phase coexistence for controlled release mechanisms.