Release behavior of poly(lactic acid-co-glycolic acid) implants containing phosphorothioate oligodeoxynucleotide

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Ophthalmology

Background:

• Phosphorothioate oligodeoxynucleotides (ODNs) are therapeutic agents with potential applications in treating ocular diseases.
• Effective delivery systems are crucial for sustained and localized release of ODNs in the eye.
• Poly(lactic acid-co-glycolic acid) (PLGA) is a biodegradable polymer commonly used in drug delivery implants.

Purpose of the Study:

• To investigate the release behavior of ODN from PLGA implants.
• To evaluate the influence of PLGA molecular weight and ODN loading on release kinetics.
• To assess the feasibility of PLGA implants for intravitreal ODN delivery for ocular disease treatment.

Main Methods:

• Fabrication of pillar-shaped PLGA implants using the heating mold method.
• In vitro release studies of ODN from PLGA implants in phosphate-buffered saline (PBS) at physiological pH.
• Evaluation of ODN release profiles across a range of PLGA molecular weights and ODN loading percentages.
• Assessment of ODN release in bovine vitreous humor.

Main Results:

• Initial burst release of approximately 20% ODN followed by pseudo-zero-order release for over 20 days from PLGA10000 implants with 8.4% ODN.
• ODN release duration was independent of PLGA molecular weight.
• Pseudo-zero-order release could be achieved by adjusting ODN loading.
• Similar release profiles were observed within the physiological pH range (7.2-7.6).
• Intact ODN release was sustained in bovine vitreous.

Conclusions:

• PLGA implants demonstrate sustained pseudo-zero-order release of ODN.
• The release kinetics are controllable by ODN loading, offering potential for tailored drug delivery.
• The findings support the potential application of these PLGA implants for intravitreal delivery in treating ocular diseases.