Pulsatile Release of Insulin from Layer‐by‐Layer Assembled Microgel Thin Films

Abstract

We describe studies concerning the construction and characterization of insulin‐impregnated poly(N‐isopropylacrylamide‐co‐acrylic acid) microgel thin films prepared by Layer‐by‐Layer (LbL) polyelectrolyte assembly. These films can be built up in a highly uniform fashion and display linear buildup dependence even up to 30 layers. Thermoresponsivity of these drug loaded films can be utilized to obtain extended pulsatile release of insulin over many cycles. Continuous thermal pulsing allows solubilization of the embedded peptide and subsequent diffusion through the film layers. The magnitude of release can be tuned based on film thickness. This type of microgel thin film construct proves to be extremely robust and can potentially pulse out constant bursts of peptide for more than one month at a time.

Poly(allylamine)‐graft‐poly(N‐isopropylacrylamide)/Poly(styrene sulfonate) Sodium Salt Multilayers: Buildup, Wettability, and Mechanical Properties

“…Lyon and coworkers first applied the LbL technique to self-assemble temperature-responsive NIPAAm-co-acrylic acid microgels and poly(allylamine) (PAH) on a surface. [16][17][18][19] Electrostatically self-assembled multilayers and capsules based on copolymers of NIPAAm with charged monomers were also described by Glinel et al [20] In such films and capsules, the electrostatically associated units can complex with the oppositely charged polymers, leaving the PNIPAAm segments for the thermo-responsiveness. Using PNIPAAm copolymers, Jaber et al measured expulsion of water molecules from the multilayers as a result of temperatureinduced dehydration of the PNIPAAm units, which illustrated the reversible thermal modulation of ion transport within the films.…”

Use of anionic polysaccharides for the preparation of insulin-containing layer-by-layer films and their pH stability

“…3). The rapid response is a merit of LbL films compared with the slower response in the insulin release from hydrogels and microcapsules [21,29]. We have previously reported that pH stability of insulin-containing LbL films under physiological temperature (37°C) is nearly comparable to that at 20°C [27,30,31].…”

“…Recently, much attention has been devoted to the development of insulin LbL films for the development of insulin formulations that can be orally administrated [21][22][23][24][25][26]. It is very clear that oral route for drug delivery is the most convenience and desired as an invasive method of drug delivery compared to injection.…”

Ethylene Glycol-Based Microgels at Solid Surfaces: Swelling Behavior and Control of Particle Number Density

“…18 Mono-and multilayer structures of microgel particles loaded with therapeutic substances can serve as drug reservoirs and release these substances from the film by temperature variations. 19 A similar concept was applied to study the uptake and release of doxorubicin. 20 Moreover, microgel multilayers are also discussed as potential antifouling coatings.…”