Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Biodegradable polymers are crucial for biomedical applications like drug delivery and tissue engineering.
• Controlled degradation in response to physiological cues is a key challenge.
• Existing polymers may lack multifunctionality or exhibit unpredictable degradation.

Purpose of the Study:

• To develop a novel class of water-soluble, multi-functional, branched biodegradable polymers.
• To investigate the in vitro and in vivo degradation characteristics of these polymers.
• To assess the biocompatibility and clearance of the developed polymers.

Main Methods:

• Synthesis of main chain degradable hyperbranched polyglycerols (HPGs) via anionic ring-opening copolymerization.
• Incorporation of acid-labile ketal groups into the polymer backbone.
• In vitro degradation studies at varying pH and temperature.
• In vivo studies in mice using tritium-labeled polymers to assess circulation half-life, biodistribution, and excretion.
• Characterization using NMR and gel permeation chromatography (GPC).

Main Results:

• Successfully synthesized water-soluble, branched HPGs (20-100 kDa) with randomly distributed ketal groups (RBHPGs).
• Demonstrated controlled in vitro degradation of RBHPGs dependent on pH, temperature, and ketal structure, yielding non-toxic products.
• Achieved good correlation between in vivo circulation half-life (2.7 h) and in vitro degradation half-life (4.3 h) for a 100 kDa RBHPG.
• RBHPGs exhibited excellent blood and tissue compatibility.
• In vivo studies showed rapid clearance, low tissue accumulation, and enhanced urinary/fecal excretion compared to non-degradable HPGs.

Conclusions:

• The developed RBHPGs offer tunable, controlled degradation profiles.
• These polymers exhibit excellent biocompatibility and efficient in vivo clearance.
• RBHPGs are promising candidates for multi-functional drug delivery systems and other biomedical applications.