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You searched for +publisher:"Georgia Tech" +contributor:("Dr. Ravi Bellamkonda"). Showing records 1 – 2 of 2 total matches.

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1. Heffernan, Michael John. Biodegradable polymeric delivery systems for protein subunit vaccines.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

The prevention and treatment of cancer and infectious diseases requires vaccines that can mediate cytotoxic T lymphocyte-based immunity. A promising strategy is protein subunit vaccines composed of purified protein antigens and immunostimulatory adjuvants, such as Toll-like receptor (TLR) agonists. In this research, we developed two new biodegradable polymeric delivery vehicles for protein antigens and TLR agonists, as model vaccine delivery systems. This work was guided by the central hypothesis that an effective vaccine delivery system would have stimulus-responsive degradation and release, biodegradability into excretable non-acidic degradation products, and the ability to incorporate various TLR-inducing adjuvants. The first vaccine delivery system is a cross-linked polyion complex micelle which efficiently encapsulates proteins, DNA, and RNA. The micelle-based delivery system consists of a block copolymer of poly(ethylene glycol) (PEG) and poly(L-lysine), cross-linked by dithiopyridyl side groups to provide transport stability and intracellular release. The second delivery system consists of solid biodegradable microparticles encapsulating proteins, nucleic acids, and hydrophobic compounds. The microparticles are composed of pH-sensitive polyketals, which are a new family of hydrophobic, linear polymers containing backbone ketal linkages. Polyketals are synthesized via a new polymerization method based on the acetal exchange reaction and degrade into non-acidic, excretable degradation products. In addition, the technique of hydrophobic ion pairing was utilized to enhance the encapsulation of ovalbumin, DNA, and RNA in polyketal microparticles via a single emulsion method. Using in vitro and in vivo immunological models, we demonstrated that the micelle- and polyketal-based vaccine delivery systems enhanced the cross-priming of cytotoxic T lymphocytes. The model vaccines were composed of ovalbumin antigen and various TLR-inducing adjuvants including CpG-DNA, monophosphoryl lipid A, and dsRNA. The results demonstrate that the cross-linked micelles and polyketal microparticles have considerable potential as delivery systems for protein-based vaccines. Advisors/Committee Members: Dr. Niren Murthy (Committee Chair), Dr. Carson Meredith (Committee Member), Dr. Julia Babensee (Committee Member), Dr. Mark Prausnitz (Committee Member), Dr. Ravi Bellamkonda (Committee Member).

Subjects/Keywords: Vaccine delivery; Drug delivery; Microencapsulation; Nanospheres; Microspheres; Nanoparticles; Polyacetal; PH-responsive; TLR ligands; Poly(I)-poly(C); Acid-degradable; Vaccines; Polymeric drug delivery systems; Biodegradable plastics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Heffernan, M. J. (2008). Biodegradable polymeric delivery systems for protein subunit vaccines. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/24787

Chicago Manual of Style (16th Edition):

Heffernan, Michael John. “Biodegradable polymeric delivery systems for protein subunit vaccines.” 2008. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021. http://hdl.handle.net/1853/24787.

MLA Handbook (7th Edition):

Heffernan, Michael John. “Biodegradable polymeric delivery systems for protein subunit vaccines.” 2008. Web. 16 Jan 2021.

Vancouver:

Heffernan MJ. Biodegradable polymeric delivery systems for protein subunit vaccines. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1853/24787.

Council of Science Editors:

Heffernan MJ. Biodegradable polymeric delivery systems for protein subunit vaccines. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/24787

2. Carpenedo, Richard L. Microsphere-mediated control of embryoid body microenvironments.

Degree: PhD, Biomedical Engineering, 2010, Georgia Tech

Embryonic stem cells (ESCs) hold great promise for treatment of degenerative disorders such as Parkinson's and Alzheimer's disease, diabetes, and cardiovascular disease. The ability of ESCs to differentiate to all somatic cell types suggests that they may serve as a robust cell source for production of differentiated cells for regenerative medicine and other cell-based therapeutics. In order for ESCs to be used effectively in clinical settings, efficient and reproducible differentiation to targeted cell types must be demonstrated. The overall objective of this project was to engineer microenvironmental control over differentiating ESCs through the formation of embryoid bodies (EBs) uniform in size and shape, and through the incorporation of morphogen-containing polymer microspheres within the interior of EBs. The central hypothesis was that morphogen delivery through incorporated polymer microspheres within a uniform population of EBs will induce controlled and uniform differentiation of ESCs. Rotary suspension culture was developed in order to efficiently produce uniform EBs in high yield. Compared to static suspension culture, rotary suspension significantly improved the production of differentiating cells and EBs over the course of 7 days, while simultaneously improving the homogeneity of EB size and shape compared to both hanging drop and static EBs. The diffusive transport properties of EBs formed via rotary suspension were investigated using a fluorescent, cell permeable dye to model the movement of small morphogenic molecules within EBs. Confocal microscopy, cryosections and EB dissociation all demonstrated that the dye was not able to fully penetrate EB, and that the larger EBs at later time points (7 days) retarded dye movement to a greater extent than earlier EBs (days 2 and 4). Polymer microspheres capable of encapsulating morphogenic factors were incorporated into EBs in order to overcome the diffusional limitations of traditional soluble delivery. The size of microspheres, microsphere coating, microsphere to cell ratio, and rotary mixing speed were all observed to influence incorporation within EBs. The use of microsphere-mediated delivery within EBs to direct cell differentiation was examined. Microsphere-mediated delivery of retinoic acid (RA) induced formation of uniquely cystic spheroids with a visceral endoderm layer enveloping a pseudo-stratified columnar epithelium, and with spatial localization of transcriptional profiles similar to the early primitive streak stage of mouse development. Continued differentiation of RA MS EBs in defined media conditions was assessed. Gene expression demonstrated that regular serum enhanced endoderm induction, serum-free media supported ectoderm differentiation, while mesoderm was most prominent in untreated EBs in full serum. In summary, this work has realized a unique approach for stem cell differentiation through modification of the internal microenvironment of ESC spheroids. This novel inside-out method toward engineering EBs demonstrated that… Advisors/Committee Members: Dr. Todd McDevitt (Committee Chair), Dr. Andrew Lyon (Committee Member), Dr. Michelle LaPlaca (Committee Member), Dr. Niren Murthy (Committee Member), Dr. Ravi Bellamkonda (Committee Member), Dr. Steve Stice (Committee Member).

Subjects/Keywords: Microsphere; Retinoic acid; Embryoid body; Embryonic stem cell; Stem cells; Tretinoin; Degeneration (Pathology); Regenerative medicine

…Spain. While work has made up a significant portion of my time at Georgia Tech and in Atlanta… …thank you for all his support. Many friends from my first few years at Georgia Tech have… 

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Carpenedo, R. L. (2010). Microsphere-mediated control of embryoid body microenvironments. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/33948

Chicago Manual of Style (16th Edition):

Carpenedo, Richard L. “Microsphere-mediated control of embryoid body microenvironments.” 2010. Doctoral Dissertation, Georgia Tech. Accessed January 16, 2021. http://hdl.handle.net/1853/33948.

MLA Handbook (7th Edition):

Carpenedo, Richard L. “Microsphere-mediated control of embryoid body microenvironments.” 2010. Web. 16 Jan 2021.

Vancouver:

Carpenedo RL. Microsphere-mediated control of embryoid body microenvironments. [Internet] [Doctoral dissertation]. Georgia Tech; 2010. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1853/33948.

Council of Science Editors:

Carpenedo RL. Microsphere-mediated control of embryoid body microenvironments. [Doctoral Dissertation]. Georgia Tech; 2010. Available from: http://hdl.handle.net/1853/33948

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