In-situ forming composite implants for periodontitis treatment: How the formulation determines system performance

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Periodontitis is a leading cause of adult tooth loss, necessitating effective local treatments.
• Composite implants offer controlled drug release for periodontitis therapy, but their formation and performance are not fully understood.
• Understanding the relationship between implant composition and drug release is crucial for optimizing treatment efficacy.

Purpose of the Study:

• To investigate the influence of poly(lactic-co-glycolic acid) (PLGA) molecular weight on the in-situ formation and drug release characteristics of composite implants.
• To elucidate the mechanisms governing drug release in PLGA/hydroxypropyl methylcellulose (HPMC) composite systems using advanced characterization techniques.

Main Methods:

• Fabrication of in-situ forming composite implants using varying molecular weights of PLGA, HPMC, and model drugs (doxycycline or metronidazole).
• Utilized advanced characterization techniques, including electron paramagnetic resonance (EPR), to analyze implant formation and water penetration.
• Physico-chemical analyses were performed to correlate formulation composition with implant structure and drug release profiles.

Main Results:

• Hydroxypropyl methylcellulose (HPMC) addition increased drug release from longer chain PLGA implants but slightly decreased it from shorter chain PLGA implants.
• EPR analysis indicated that HPMC significantly enhanced water penetration into longer chain PLGA formulations, leading to more porous implant structures.
• The increased porosity and hydrophobicity of longer chain PLGA, facilitated by HPMC, resulted in accelerated drug release compared to shorter chain PLGA systems.

Conclusions:

• The molecular weight of PLGA is a critical factor determining the drug release behavior in HPMC-containing composite implants.
• The observed opposite effects of HPMC on drug release are attributed to differences in water penetration and implant porosity, influenced by PLGA chain length.
• This study provides fundamental insights into the mechanisms controlling drug release from in-situ forming implants, paving the way for optimized periodontitis therapies.