Ultrasonic atomization and subsequent polymer desolvation for peptide and protein microencapsulation into...

Area of Science:

• Biomaterials Engineering
• Drug Delivery Systems
• Pharmaceutical Technology

Background:

• Peptide and protein microencapsulation into poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) microspheres presents significant challenges for sterile manufacturing and large-scale production.
• Existing methods often struggle to meet the stringent requirements for aseptic processing and scalability.

Purpose of the Study:

• To investigate the feasibility of a novel ultrasonic atomization technique for entrapping peptides and proteins into PLA and PLGA microspheres.
• To develop a method suitable for up-scaling and aseptic processing in pharmaceutical manufacturing.

Main Methods:

• Utilized ultrasonic atomization of polymer solutions followed by organic solvent extraction using a hardening agent.
• Evaluated critical atomization parameters, polymer solvent and hardening agent cohesion properties (f(p), f(h)), and their impact on encapsulation and release.
• Characterized microsphere size (0.1-100 µm) and drug loading efficiencies for various peptides and proteins.

Main Results:

• Defined specific fractional cohesion parameter ranges for effective polymer solvents and hardening agents.
• Achieved high encapsulation efficiencies (63-93%) for slightly water-soluble octapeptide vapreotide pamoate, while modest efficiencies (12-35%) were observed for freely water-soluble bovine serum albumin and tetrapeptide thymocartin.
• Demonstrated sustained drug release profiles, with release extending over 100 days for BSA in PLA and 20 days for vapreotide pamoate in PLGA 50:50 and thymocartin in PLA.
• Successfully adapted the method for aseptic processing within a laminar air-flow cabinet, yielding sterile microspheres.

Conclusions:

• The novel ultrasonic atomization method offers a promising approach for scalable and aseptic microencapsulation of peptides and proteins.
• The method's adaptability to aseptic conditions makes it suitable for industrial pharmaceutical production.
• Further optimization based on polymer and drug properties can enhance encapsulation efficiency and control release kinetics.