Nanoparticles Of PLGA With Encapsulated Insulin For Oral Controlled Release For Diabetes Treatment
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PublisherThe University of Arizona.
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AbstractInsulin, a relatively low molecular weight protein has been used for decades in the treatment of diabetes; it has well-defined properties and delivery requirements. Due to the current increase of diabetes in the world improved insulin delivery systems could significantly influence the treatment of diabetes and the quality of life of the affected people. The main objective of this work was to encapsulate insulin in polymer nanoparticles of Poly (DL-Lactic-Co-Glycolic Acid) (PLGA) and poly vinyl alcohol (PVA). Preliminary results of these functional therapeutic nanoparticles prepared with PVA and PLGA by using a double emulsion method (water/oil/water) were obtained in terms of encapsulation efficiency and effective insulin release from the nanoparticles. Assessing the bioactivity of insulin once encapsulated and released is not trivial, thus an indirect protein assay was developed to effectively and easily assess the activity of proteins going through these processes. Trypsin, a proteolitic enzyme was used as model protein to investigate the biological activity of encapsulated and released biomolecules. The activity of trypsin towards a synthetic substrate, DL-BAPNA was used to measure the enzyme kinetics and activity before encapsulation, while encapsulated and after the enzyme was released from the nanoparticles. Results show that the enzyme maintained substantial activity while encapsulated and after its release. It is anticipated that the biological activity after being released from the nanoparticles will remain biologically active, however, biological assays remain to be performed to corroborate this argument. In addition to release experiments with trypsin and insulin, other proteins were also studied. In all cases the release form the nanoparticles at 37 °C exhibited a three stage release process, The release process will be modeled according to developed mathematical models that consider initial burst of molecules, degradation of polymer and diffusion of molecules from the nanoparticles.
Degree ProgramGraduate College