Biodegradable salicylate‐based poly(anhydride‐ester) microspheres for controlled insulin delivery

Abstract

Salicylate-based poly(anhydride-esters) (PAEs) chemically incorporate salicylic acid (SA) into the polymer backbone, which is then delivered in a controlled manner upon polymer hydrolysis. In this work, a salicylate-based PAE is a carrier to encapsulate and deliver insulin. Polymer microspheres were formulated using a water/oil/water double-emulsion solvent evaporation technique. The microspheres obtained had a smooth surface, high protein encapsulation efficiency, and relatively low emulsifier content. Insulin was released in vitro for 15 days, with no signs of aggregation or unfolding of the secondary structure. The released insulin also retained bioactivity in vitro. Concurrently, SA was released from the microspheres with polymer degradation and anti-inflammatory activity was observed. Based upon these results, the formulated microspheres enable simultaneous delivery of insulin and SA, both retaining bioactivity following processing.

Polyactives: controlled and sustained bioactive release via hydrolytic degradation

“…96, 98 Encapsulation of proteins into bioactive-based polymer microspheres was also achieved using the standard water/oil/water emulsion technique. 96, 98 One example is the encapsulation of insulin into SA-based PAE microspheres, which yielded microspheres with smooth spherical geometry, high insulin loading (4.1%) and high insulin loading efficiency (~82.6%). Insulin and SA were concurrently released from the microspheres in PBS for about two weeks and their in vitro and in vivo bioactivities were well maintained.…”

“…Insulin and SA were concurrently released from the microspheres in PBS for about two weeks and their in vitro and in vivo bioactivities were well maintained. 98 …”

Injectable microspheres for extended delivery of bioactive insulin and salicylic acid

“…No broken spheres were observed, and microsphere geometry, surface smoothness, and sizes agree with previous work. 9 In general, all microspheres displayed a smooth surface and sizes of ~13 µm (12.3 ± 6.4 µm for insulin-loaded and 13.9 ± 7.6 µm for nonloaded microspheres).…”

“…[14][15][16][17] We previously tested the in vitro activity of the insulin and SA released from microspheres, demonstrating that SA reduced tumor necrosis factor-α (TNF-α) secretion from lipopolysaccharide (LPS)-activated macrophages, whereas the insulin increased phosphorylated Akt level in rat myoblasts. 9 This study deepens the understanding of dual SA/insulin delivery and further investigates the in vivo pharmacokinetics of this dual delivery system and its effect on blood glucose levels. Both SA and insulin are detected in mice sera over an extended period of time (at least 4 days and 12 h, respectively).…”

Glucose-responsive insulin release: Analysis of mechanisms, formulations, and evaluation criteria

“…To directly evaluate the biological activity of insulin, a cell-based assay is typically conducted, where the phosphorylation of protein kinase B (Akt) of the cells is quantified after the cells being incubated with the medium containing the released insulin [23,70,103]. This assay is based on an insulin-induced intracellular process.…”