Recombinant human growth hormone poly(lactic-co-glycolic acid) microsphere formulation development.

Area of Science:

• Biotechnology
• Polymer Science
• Pharmacology

Background:

• Sustained release formulations aim to improve therapeutic protein delivery.
• Recombinant human growth hormone (rhGH) requires stable delivery systems for efficacy.
• Poly(lactic-co-glycolic acid) (PLGA) is a key biodegradable polymer for drug delivery microspheres.

Purpose of the Study:

• To develop and evaluate a sustained release formulation of rhGH using PLGA microspheres.
• To ensure protein integrity during microencapsulation and release.
• To establish in vivo-in vitro release correlations and assess in vivo efficacy.

Main Methods:

• Microencapsulation of rhGH in PLGA using conventional and novel cryogenic processes.
• In vitro and in vivo release kinetic studies in animal models (rhesus monkeys).
• Assessment of protein integrity, biological activity, and immunogenicity.
• Safety evaluation in growth hormone-deficient adults.

Main Results:

• The cryogenic process achieved continuous release of biologically active, non-immunogenic rhGH.
• Continuous rhGH administration in juvenile rhesus monkeys showed a greater IGF-I response than daily dosing.
• The rhGH PLGA formulation was safe and well-tolerated in growth hormone-deficient adults.
• Established correlation between in vitro and in vivo release profiles.

Conclusions:

• The novel cryogenic process is effective for producing stable, sustained-release rhGH PLGA formulations.
• Continuous rhGH delivery may offer improved efficacy and reduced total dosage compared to daily administration.
• This PLGA formulation and development strategy serve as a model for future therapeutic protein delivery systems.