A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Engineering

Background:

• Controlled drug delivery systems are crucial for therapeutic efficacy and patient compliance.
• Bioresorbable polymers offer advantages for implantable and biodegradable drug delivery devices.
• Achieving zero-order release kinetics, especially for macromolecules, remains a challenge.

Purpose of the Study:

• To design and characterize a zero-order bioresorbable reservoir delivery system (BRDS).
• To evaluate the system's capability for diffusional or osmotically controlled release of model drugs, including macromolecules.
• To investigate the influence of polymer composition and processing on membrane properties and drug release.

Main Methods:

• Fabrication of hollow cylindrical poly (lactic acid) (PLA): polyethylene glycol (PEG) membranes via casting.
• Characterization of membrane physical properties using solid-state thermal analysis (Differential Scanning Calorimetry).
• In vitro dissolution studies using model drugs (5-fluorouracil and FITC-dextran) and monitoring release via UV or fluorescence spectroscopy.

Main Results:

• PLA:PEG membranes processed at 25°C exhibited desirable thermal properties for drug delivery.
• The BRDS demonstrated zero-order release of 5-fluorouracil for up to 6 weeks.
• Zero-order release of FITC-dextran (various molecular weights) was achieved, independent of molecular weight.
• Release rate of FITC-dextran correlated linearly with the osmotic gradient (ΔPi).

Conclusions:

• Polyethylene glycol inclusion in PLA membranes facilitates the manufacture of uniform, permeable systems.
• The BRDS can be engineered for osmotically controlled release of model macromolecules.
• This technology holds promise for advanced, controlled drug delivery applications, particularly for biologics.