Drug delivery systems based on pharmaceutically active ionic liquids and biocompatible poly(lactic acid)

Area of Science:

• Materials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Poly(l-lactic acid) (PLLA) is a biodegradable polymer with potential in drug delivery.
• Incorporating pharmaceutically active ionic liquids (API-ILs) into PLLA can create novel drug delivery systems.
• Controlling the properties of these PLLA-API-IL membranes is crucial for effective drug release.

Purpose of the Study:

• To prepare and characterize PLLA membranes containing two different API-ILs: 1-methyl-3-butyl-imidazolium ibuprofenate (C4MImIbu) and lidocainium ibuprofenate (LidIbu).
• To investigate the influence of API-IL nature and content on the morphology, crystallinity, and drug mobility within the PLLA matrix.
• To evaluate the performance of these membranes as drug delivery systems with tunable release kinetics.

Main Methods:

• Film casting from solvent evaporation was used to prepare PLLA membranes with varying API-IL concentrations.
• Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and X-ray Scattering (WAXS, SAXS) were employed to analyze membrane morphology and crystallinity.
• Nuclear Magnetic Resonance (NMR) spectroscopy (1H and 1H-13C CP-MAS) was used to assess API-IL mobility.
• In vitro drug release studies were conducted to evaluate the delivery performance.

Main Results:

• LidIbu at 20 wt% acted as a plasticizer, forming homogeneous PLLA membranes.
• C4MImIbu at 20 wt% induced phase separation, creating porous PLLA membranes.
• Increased LidIbu content (50 wt%) also led to phase separation.
• API-IL mobility varied: C4MImIbu showed high mobility, while LidIbu mobility was content-dependent.
• Drug release kinetics were tunable based on API-IL type and concentration, with plasticizing API-ILs yielding sustained release and porogenic API-ILs yielding faster release.

Conclusions:

• The nature and content of API-ILs significantly influence the morphology and crystallinity of PLLA membranes.
• Membrane morphology and API-IL mobility directly impact drug release kinetics.
• These PLLA-API-IL membranes offer a versatile platform for developing tunable drug delivery systems.