Mechanistic Evaluation of the Opposite Effects on Initial Burst Induced by Two Similar Hydrophilic Additives From Octreotide Acetate-Loaded PLGA Microspheres

Abstract

The purpose of the present study was to make a detailed comparison of 2 similar additives about their opposite effects on the initial burst of octreotide acetate from poly(lactic-co-glycolic acid) microspheres. We focused on identifying the key factor that influenced the initial burst of microspheres induced by small hydrophilic additives. The apparent reason resulting in such differences was different pore closing rates on the surface of these 2 batches. However, the potential mechanism was still unknown. To compare with the single-additive system, these 2 additives were coencapsulated together into the same formulation. Of surprise, the inhibition effect of glucose on burst release somehow disappeared and even turned out to be opposite. This phenomenon greatly reminds us that there must be some interactions between glucose and polymer, which are likely to be disturbed by coencapsulated CaCl₂. However, small amount of additive can hardly make any detected difference. Therefore, additive-loaded microspheres without drug were prepared to further investigate the potential factors. Under this condition, differences were found. The key factor for glucose-induced accelerated pore closure and reduction in initial burst was the formation of hydrogen bonds between the glucose molecule and the polymer matrix.

Keywords: CaCl(2); glucose; hydrogen bonds; initial burst; pore closing.