Self-healing polymers microencapsulate biomacromolecules without organic solvents | Posted on:2010-08-16 | Degree:Ph.D | Type:Thesis | University:University of Michigan | Candidate:Reinhold, Samuel E., III | Full Text:PDF | GTID:2441390002976563 | Subject:Health Sciences | Abstract/Summary: | | Microencapsulation of medicines in modern polymeric biomaterials plays a crucial role in success of long-term injectable depots, drug-eluting stents, tissue engineering scaffolds, and blood-circulating nanoparticles. Until now, drugs are most commonly dissolved in organic solvent, which has several disadvantages. Described here is a new microencapsulation paradigm based on the polymer's own natural "self-healing" capacity to microencapsulate biomacromolecules in aqueous media without use of organic solvents. Self-healing microencapsulation (SM) was shown to reproducibly produce poly(lactic- co-glycolic acid) (PLGA) microparticles with high peptide and protein loadings of 1-10% (w/w), that was dependent on porous SM-microparticle excipients (e.g. MgCO3 and trehalose), manufacturing parameters, protein loading solution concentration, and overall porosity. Confocal microscopy of microspheres loaded with fluorescently-labeled BSA showed loaded protein concentrated in submicron domains throughout the microparticle. A model therapeutic peptide, leuprolide acetate, was encapsulated successfully via the self-healing microencapsulation technique. Controlled release over 30 and 60 days for both proteins and the peptide was demonstrated. Self-healing microencapsulation of a model protein lysozyme showed virtually no aggregation or enzymatic activity loss when high amounts of sucrose were loaded in conjunction with the protein, which is currently not possible with traditional encapsulation methods due to the resulting high initial burst release and low encapsulation efficiencies. Self-healing encapsulated BSA showed virtually no acid-induced aggregation (< 2%) after 30 d of release indicating the ability to successfully neutralize acid PLGA using the new encapsulation approach. The self-healing polymer process was strongly affected by different Hofmeister salts, known for their ability to influence interfacial tension. These data were consistent with the hypothesis that the polymer self-healing is driven in part by the high interfacial tension between the hydrophobic polymer and water which causes a minimization of interfacial area. Protein in microspheres loaded via self-healing microencapsulation was not exposed to the numerous destabilizing processes normally associated with protein-loaded microsphere manufacturing. Terminal sterilization of PLGA microspheres without concerns of protein stability is now theoretically possible. The new paradigm opens the door to improved compatibility with large biotechnology-derived drugs, potentially lower manufacturing cost, the ability to create new biomaterial architectures, and more practical use among other scientists and clinicians. | Keywords/Search Tags: | Self-healing, Polymer, Microencapsulation, Organic, New | | Related items |
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