Synthesis and characterization of stimuli responsive block copolymers, self-assembly behavior and applications

Water-soluble stimuli responsive block copolymers are a rapidly emerging class of materials with great potential in biomedical and technological applications. In this work a novel class of pentablock copolymers are synthesized via atom transfer radical polymerization techniques and their stimuli-responsive self-assembly properties are characterized. Aqueous solutions of these materials are observed to form micelles and hydrogels in response to changes in both temperature and pH. Cryogenic transmission electron microscopy (cryo-TEM) and small angle neutron and X-ray scattering (SANS and SAXS) techniques are used to investigate the nanoscale structures formed by these pentablock copolymers in solution. The gel structure and mechanical properties are investigated with SANS and rheological techniques. The multi-responsive properties of these materials are utilized to formulate a stimuli responsive drug delivery formulation that exhibits thermoreversible gelation and pH dependent release rate of model drugs

Thermoresponsive reversible behavior of multistimuli pluronic-based pentablock copolymer at the air-water interface

Surface behavior of the pH- and thermoresponsive amphiphilic ABCBA pentablock copolymer has been studied with respect to the environmental conditions. We demonstrate that the pentablock copolymer poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl methacrylate)) possesses reversible temperature changes at the air-water interface in a narrow pH range of the water subphase. Significant diversity in the surface morphology of pentablock copolymer monolayers at different pH and temperatures observed were related to the corresponding reorganization of central and terminal blocks. Remarkable reversible variations of the surface pressure observed for the Langmuir monolayers at pH 7.4 in the course of heating and cooling between 27 and 50°C is associated with conformational transformations of terminal blocks crossing the phase line in the vicinity of the lower critical solution temperature point. The observed thermoresponsive surface behavior can be exploited for modeling of the corresponding behavior of pentablock copolymers adsorbed onto various biointerfaces for intracellular delivery for deeper understanding of stimuli-responsive transformations relevant to controlled drug and biomolecules release and retention

Design of a Protective Single-Dose Intranasal Nanoparticle-Based Vaccine Platform for Respiratory Infectious Diseases

Despite the successes provided by vaccination, many challenges still exist with respect to controlling new and re-emerging infectious diseases. Innovative vaccine platforms composed of adaptable adjuvants able to appropriately modulate immune responses, induce long-lived immunity in a single dose, and deliver immunogens in a safe and stable manner via multiple routes of administration are needed. This work describes the development of a novel biodegradable polyanhydride nanoparticle-based vaccine platform administered as a single intranasal dose that induced long-lived protective immunity against respiratory disease caused by Yesinia pestis, the causative agent of pneumonic plague. Relative to the responses induced by the recombinant protein F1-V alone and MPLA-adjuvanted F1-V, the nanoparticle-based vaccination regimen induced an immune response that was characterized by high titer and high avidity IgG1 anti-F1-V antibody that persisted for at least 23 weeks post-vaccination. After challenge, no Y. pestis were recovered from the lungs, livers, or spleens of mice vaccinated with the nanoparticle-based formulation and histopathological appearance of lung, liver, and splenic tissues from these mice post-vaccination was remarkably similar to uninfected control mice

Multi-Faceted Scientific Strategies Toward Better Solid-State Lighting of Phosphorescent OLEDs

This project has advanced solid-state lighting (SSL) by utilizing new phosphorescent systems for use in organic light-emitting diodes (OLEDs). The technical approach was two-fold: a) Targeted synthesis and screening of emitters designed to exhibit phosphorescence with maximized brightness in the solid state; and b) Construction and optimizing the performance of monochromatic and white OLEDs from the best new emitters to improve performance metrics versus the state of the art. The phosphorescent systems were screened candidates among a large variety of recentlysynthesized and newly-designed molecular and macromolecular metal-organic phosphors. The emitters and devices have been optimized to maximize light emission and color metrics, improve the long-term durability of emitters and devices, and reduce the manufacturing cost both by simplifying the process flow and by seeking less expensive device components than common ones. The project succeeded in all these goals upon comparison of the best materials and devices investigated vs. the state of the art of the technology

Synthesis and characterization of stimuli responsive block copolymers, self-assembly behavior and applications

Water-soluble stimuli responsive block copolymers are a rapidly emerging class of materials with great potential in biomedical and technological applications. In this work a novel class of pentablock copolymers are synthesized via atom transfer radical polymerization techniques and their stimuli-responsive self-assembly properties are characterized. Aqueous solutions of these materials are observed to form micelles and hydrogels in response to changes in both temperature and pH. Cryogenic transmission electron microscopy (cryo-TEM) and small angle neutron and X-ray scattering (SANS and SAXS) techniques are used to investigate the nanoscale structures formed by these pentablock copolymers in solution. The gel structure and mechanical properties are investigated with SANS and rheological techniques. The multi-responsive properties of these materials are utilized to formulate a stimuli responsive drug delivery formulation that exhibits thermoreversible gelation and pH dependent release rate of model drugs.</p

Synthesis and Characterization of Stimuli Responsive Block Copolymers, Self-Assembly Behavior and Applications

The central theme of this thesis work is to develop new block copolymer materials for biomedical applications. While there are many reports of stimuli-responsive amphiphilic [19-21] and crosslinked hydrogel materials [22], the development of an in situ gel forming, pH responsive pentablock copolymer is a novel contribution to the field, Figure 1.1 is a sketch of an ABCBA pentablock copolymer. The A blocks are cationic tertiary amine methacrylates blocked to a central Pluronic F127 triblock copolymer. In addition to the prerequisite synthetic and macromolecular characterization of these new materials, the self-assembled supramolecular structures formed by the pentablock were experimentally evaluated. This synthesis and characterization process serves to elucidate the important structure property relationships of these novel materials, The pH and temperature responsive behavior of the pentablock copolymer were explored especially with consideration towards injectable drug delivery applications. Future synthesis work will focus on enhancing and tuning the cell specific targeting of DNA/pentablock copolymer polyplexes. The specific goals of this research are: (1) Develop a synthetic route for gel forming pentablock block copolymers with pH and temperature sensitive properties. Synthesis of these novel copolymers is accomplished with ATRP, yielding low polydispersity and control of the block copolymer architecture. Well defined macromolecular characteristics are required to tailor the phase behavior of these materials. (2) Characterize relationship between the size and shape of pentablock copolymer micelles and gel structure and the pH and temperature of the copolymer solutions with SAXS, SANS and CryoTEM. (3) Evaluate the temperature and pH induced phase separation and macroscopic self-assembly phenomenon of the pentablock copolymer. (4) Utilize the knowledge gained from first three goals to design and formulate drug delivery formulations based on the multi-responsive properties of the pentablock copolymer. Demonstrate potential biomedical applications of these materials with in vitro drug release studies from pentablock copolymer hydrogels. The intent of this work is to contribute to the knowledge necessary for further tailoring of these, and other functional block copolymer materials for biomedical applications

Supramolecular self-assembly of multiblock copolymers in aqueous solution

A unique pH-dependent phase behavior from a copolytner micellar solution to a collapsed hydrogel with micelles ordered in a hexagonal phase was observed. Small-angle neutron scattering (SANS) was used to follow the pH-dependent structural evolution of micelles formed in a solution of a pentablock copolymer consisting of poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl methacrylate)) (PDEAEM 25-b-PEO 100-b-PPO 65-b-PEO 100-b-PDEAEM 25). Between pH 3.0 and pH 7.4, we observed the presence of charged spherical micelles. Increasing the pH of the micelle solution above pH 7.4 resulted in increasing the size of the micelles due to the increasing hydrophobicity of the PDEAEM blocks above their pK a of 7.6. The increase in size of the spherical micelles resulted in a transition to a cylindrical micelle morphology in the pH range 8.1-10.5, and at pH > 11, the copolymer solution undergoes macroscopic phase separation. Indeed, the phase separated copolymer sediments and coalesces into a hydrogel structure that consists of 25-35 wt% water. Small-angle X-ray scattering (SAXS) clearly indicated that the hydrogel has a hexagonal ordered phase. Interestingly, the process is reversible, as lowering of the pH below 7.0 leads to rapid dissolution of the solid into homogeneous solution. We believe that the hexagonal structure in the hydrogel is a result of the organization of the cylindrical micelles due to the increased hydrophobic interactions between the micelles at 70°C and pH 11. Thus we have developed a pH-/ temperature-dependent, reversible hierarchically self-assembling block copolymer system with structures spanning nano- to microscale dimensions.Reprinted (adapted) with permission from Langmuir, 22 (4): pp. 1469-1473, doi: 10.1021/la0527691. Copyright 2006 American Chemical Society.</p

pH- and temperature-dependent phase behavior of a PEO-PPO-PEO-based pentablock copolymer in aqueous media

We investigated the structural features of micelles formed by the self-association of the pentablock copolymer poly [N,N -(diethyl amino)ethyl methacrylate]-block-poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethyleneoxide)-block-poly [N,N -(diethylamino)ethyl methacrylate] (PDEAEM-PEO-PPO-PEO-PDEAEM) in aqueous solutions by using small-angle neutron scattering SANS. The pentablock copolymer solutions exhibit micellar and gel phases in response to changes in both the temperature and pH by virtue of (1) the lower critical solution temperature of the PPO blocks and (2) the polyelectrolyte character of the pendant PDEAEM blocks. Two modeling schemes were employed to describe the SANS data of semidilute copolymer solutions at higher temperature as they contain interacting charged micelles at pHThis article is from Physical Review E - Statistical, Nonlinear, and Soft Matter Physics 78 (2008): 021802, doi: 10.1103/PhysRevE.78.021802.</p

Thermoresponsive reversible behavior of multistimuli pluronic-based pentablock copolymer at the air-water interface

Surface behavior of the pH- and thermoresponsive amphiphilic ABCBA pentablock copolymer has been studied with respect to the environmental conditions. We demonstrate that the pentablock copolymer poly((diethylaminoethyl methacrylate)-b-(ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)-b-(diethylaminoethyl methacrylate)) possesses reversible temperature changes at the air-water interface in a narrow pH range of the water subphase. Significant diversity in the surface morphology of pentablock copolymer monolayers at different pH and temperatures observed were related to the corresponding reorganization of central and terminal blocks. Remarkable reversible variations of the surface pressure observed for the Langmuir monolayers at pH 7.4 in the course of heating and cooling between 27 and 50°C is associated with conformational transformations of terminal blocks crossing the phase line in the vicinity of the lower critical solution temperature point. The observed thermoresponsive surface behavior can be exploited for modeling of the corresponding behavior of pentablock copolymers adsorbed onto various biointerfaces for intracellular delivery for deeper understanding of stimuli-responsive transformations relevant to controlled drug and biomolecules release and retention.Reprinted with permission from Langmuir 23 (2007), pp.25-30, doi: 10.1021/la061547f. Copyright 2007 American Chemical Society.</p