Abstract
Self-regulated drug delivery systems (DDS) are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, (2-(dimethyl amino) ethyl aminoacrylate) (PDMAEMA) and topped of with polymer/glucose oxidase (GOD) layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid) (PAA) were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate) (PSS) instead of GOD.
Highlights
Diabetes Mellitus, or hyperglycemia, is a chronic condition characterized by high glucose concentration in blood due to the insufficient amount of functional insulin [1]
Change in pH of solutions is caused by the production of gluconic acid from glucose catalyzed by glucose oxidase (GOD) [7,8]
The PDMAEMA thin films exhibit a rougher topography and there are pore-like structures on the surface which may contribute to its drug release
Summary
Diabetes Mellitus, or hyperglycemia, is a chronic condition characterized by high glucose concentration in blood due to the insufficient amount of functional insulin [1]. Insulin pens and syringes can cause tissue damage with repeated use and they provide immediate drug release in which the system releases the drug all at once. They have the tendency to cause side-effects like hypoglycemia and anaphylaxis [2]. Drugs have a minimum effective concentration (MEC) and a minimum toxic concentration (MTC) Various studies for the use of pH-responsive polymers have been studied and incorporated in films to achieve controlled insulin release. The drug release profile and on-off mechanism in response of glucose of the films were characterized using Atomic UV-Vis spectroscopy while film characterization was done using atomic force microscopy (AFM) and dynamic light scattering (DLS)
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