pH-Responsive Polyethylene Glycol Monomethyl Ether-ε-Polylysine-G-Poly (Lactic Acid)-Based Nanoparticles as Protein...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Poly(lactic acid) carriers face limitations in protein delivery due to harsh internal pH.
• Developing pH-responsive materials is crucial for protecting sensitive protein therapeutics.

Purpose of the Study:

• To synthesize and evaluate pH-responsive comb-shaped block copolymer nanoparticles (PEP) for sustained protein delivery.
• To assess the pH-responsive behavior, protein stability, release kinetics, and biocompatibility of PEP nanoparticles.

Main Methods:

• Synthesis of polyethylene glycol monomethyl ether-ε-polylysine-g-poly (lactic acid) (PEP) copolymer.
• Characterization of PEP nanoparticles for pH-responsive properties using quantitative ratiometric results.
• Assessment of protein (bovine serum albumin) stability via circular dichroism spectroscopy.
• In vitro and in vivo studies for sustained protein release evaluation.
• Cytotoxicity assays using HL-7702 cells and acute toxicity tests in Kunming mice.

Main Results:

• PEP nanoparticles demonstrated pH-responsive behavior, adjusting internal pH to milder levels.
• Proteins encapsulated in PEP nanoparticles exhibited enhanced stability compared to poly(lactic acid) nanoparticles.
• Sustained release of bovine serum albumin was achieved both in vitro and in vivo.
• PEP carriers showed good cell compatibility and no significant toxicity in animal models.

Conclusions:

• PEP nanoparticles represent a promising advanced material for the sustained and stabilized delivery of protein therapeutics.
• The pH-responsive nature of PEP enhances protein integrity, overcoming limitations of traditional carriers.
• PEP nanoparticles exhibit excellent biocompatibility and safety profiles for potential therapeutic applications.