Encapsulation of PROLI/NO in biodegradable microparticles

Abstract

Biodegradable hydrophilic polymers poly-lactic-co-glycolic acid (PLGA) and polyethylene oxide-co-lactic acid (PELA) were used to encapsulate a small hydrophilic prodrug (PROLI/NO) as a strategy to deliver nitric oxide (NO) by inhalation. The microparticles were prepared using double emulsion and solvent evaporation, followed by freeze-drying. The NO release kinetics were characterized by three parameters: the maximum concentration of NO per unit weight of microparticles, C_max (nM mg⁻¹); the window of time for which the concentration exceeded 50% of C_max, W₅₀ (min); and the initial rate of release, R_i (nM mg⁻¹ min⁻¹). PLGA-based microparticles did not encapsulate PROLI/NO. PELA-based microparticles demonstrated an entrapment efficiency rate of 43%, a mass median diameter of 2.3 µm, and NO release in a physiological buffer characterized by C_max = 123, W₅₀ = 4.11, and R_i = 78.7. Addition of gelatin as a hydrophilic binding moiety in the first emulsion allowed PLGA-based microparticles to encapsulate PROLI/NO; however, the mass median diameter was too large for inhalation (23.5 µm). It is concluded that the hydrophilic polyethylene glycol-moiety in PELA allows for efficient encapsulation of PROLI/NO, and PELA-based microparticles might be a strategy to generate a stable inhalable form of NO.

Keywords: :

• Pulmonary hypertension
• inhalation
• nitric oxide
• PELA
• PLGA
• microsphere