Browsing by Author "Washington, Katherine E."
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item Fine-tuning Thermoresponsive Functional Poly(ε-caprolactone)s to Enhance Micelle Stability and Drug Loading(Royal Society of Chemistry, 2015-01-16) Rainbolt, Elizabeth A.; Miller, J. B.; Washington, Katherine E.; Senevirathne, Suchithra A.; Biewer, Michael C.; Siegwart, D. J.; Stefan, Mihaela C.; 55039821 (Stefan, MC); Biewer, Michael C.; Stefan, Mihaela C.Block copolymers synthesized by the ring-opening polymerization of γ-2-[2-(2-methoxyethoxy)ethoxy]ethoxy-ε-caprolactone (ME₃CL), γ-2-methoxyethoxy-ε-caprolactone (ME₁CL), and ε-caprolactone (CL) are reported. Previously, diblock copolymers of PME₃CL-b-PME₁CL displayed excellent thermoresponsive tunability (31-43 ⁰C) and self-assembled into micelles with moderate thermodynamic stability. In this report, two strategies are employed to enhance thermodynamic stability of PME₃CL/PME₁CL-type block copolymer micelles while maintaining their attractive thermoresponsive qualities: modification of the end group position and alteration of hydrophobic block composition by using both ME₁CL and CL. These new thermoresponsive amphiphilic block copolymers showed lower critical micelle concentration (CMC) values by one order of magnitude and formed thermodynamically stable micelles. Furthermore they demonstrated good biocompatibility and up to 4.97 wt% doxorubicin loading, more than double the amount loaded into the PME₃CL-type polymeric micelles previously reported.Item Linear and Star-Like Substituted Polycaprolactones for Enhanced Delivery of Doxorubicin(2017-08) Washington, Katherine E.; Stefan, Mihaela C.Doxorubicin is a poorly water soluble chemotherapeutic drug used in the treatment of many cancers. However, due to its toxic side effects, there has been a lot of effort to develop better delivery methods for this drug to alleviate some of the toxicity and to improve its efficacy. Encapsulation of doxorubicin in polymeric micellar drug delivery systems offer an opportunity to improve this delivery by improved solubility and a more controlled release of the drug to tumor sites. Substituted poly(caprolactone)s are a desirable material to use to form amphiphilic block copolymers due to their tunable properties. Depending on the substituent used, the size, stability, degradation rate, and hydrophilicity or hydrophobicity of the micelle can be adjusted. One drawback of micelle drug delivery systems is their tendency to have low drug loading capacities. In this dissertation, several drug delivery systems were designed in order to increase the amount of doxorubicin loading in polymeric micelles. The design and recent advances of polymeric drug delivery systems featuring polyesters is discussed in Chapter 1. Polyesters are attractive drug delivery materials due to their biocompatibility and biodegradability. Many systems have been designed using these systems including those that are stimuli-responsive, designed for a more controlled release of the encapsulated cargo, and those that have targeting to allow for a better accumulation of the drug delivery vehicles at tumor sites. Different systems that have been developed in recent years using polyesters are discussed in this chapter. Chapter 2 describes a comparison of linear and 4-arm star-like block copolymers synthesized from amphiphilic polycaprolactones with a tri(ethylene glycol) substituted polycaprolactone as the hydrophilic block and unsubstituted poly(caprolactone) as the hydrophobic segment. The linear and star-like block copolymers are compared in terms of their thermodynamic stability, degradation, size, and drug loading capabilities, with the star-like structure used as a way to improve the loading of doxorubicin. In Chapter 3, two star-like polycaprolactones featuring either four or six arms are compared in terms of their properties and drug loading abilities. In addition, these polymers are synthesized with a tri(ethylene glycol) substituted poly(caprolactone) hydrophilic block and a ethoxy substituted hydrophobic block, which are shown to have thermally controlled drug release. Chapter 4 focuses on improving the loading of doxorubicin in polymeric micelles through the combination loading of doxorubicin with resveratrol, a polyphenolic compound that has cardioprotective and chemosensitizing properties. Resveratrol, when loaded in combination with doxorubicin, increases the amount of doxorubicin encapsulated in the micelle significantly. This can be a way to improve loading of the chemotherapeutic drug, while also decreasing some of its toxic side effects.Item Novel Chlorhexidine-Loaded Polymeric Nanoparticles for Root Canal TreatmentQuiram, Gina; Montagner, Francisco; Palmer, Kelli L.; Stefan, Mihaela C.; Washington, Katherine E.; Rodrigues, Danieli C.; Quiram, Gina; Palmer, Kelli L.; Stefan, Mihaela C.; Washington, Katherine E.; Rodrigues, Danieli C.Persistence of microorganisms in dentinal tubules after root canal chemo-mechanical preparation has been well documented. The complex anatomy of the root canal and dentinal buffering ability make delivery of antimicrobial agents difficult. This work explores the use of a novel trilayered nanoparticle (TNP) drug delivery system that encapsulates chlorhexidine digluconate, which is aimed at improving the disinfection of the root canal system. Chlorhexidine digluconate was encapsulated inside polymeric self-assembled TNPs. These were self-assembled through water-in-oil emulsion from poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA), a di-block copolymer, with one hydrophilic segment and another hydrophobic. The resulting TNPs were physicochemically characterized and their antimicrobial effectiveness was evaluated against Enterococcus faecalis using a broth inhibition method. The hydrophilic interior of the TNPs successfully entrapped chlorhexidine digluconate. The resulti ng TNPs had particle size ranging from 140–295 nm, with adequate encapsulation efficiency, and maintained inhibition of bacteria overItem Peg Based Anti-Cancer Drug Conjugated Prodrug Micelles for the Delivery of Anti-Cancer Agents(Royal Soc Chemistry, 2015-12-09) Senevirathne, Suchithra A.; Washington, Katherine E.; Biewer, Michael C.; Stefan, Mihaela C.; 55039821 (Stefan, MC); Senevirathne, Suchithra A.; Washington, Katherine E.; Biewer, Michael C.; Stefan, Mihaela C.Due to the high cost and uncertain success of new drug development, tremendous effort is devoted to increasing the efficacy of established anti-cancer drugs. Development of polymer prodrug conjugates has evolved recently in the nano-medicine field for cancer diagnosis and treatment. The major advantage of using polymer drug conjugates is that the chemical and physical properties of polymers can be tuned to increase the efficacy and to reduce the toxicity of the drug. The stimuli responsiveness provides the release of the prodrug in a controlled manner which avoids undesired side effects, organ damage, and toxicity caused by the fluctuations associated with periodic administration. A large number of anti-cancer drug polymer conjugates have been studied for cancer therapy due to their promising clinical applications in chemotherapy. In this paper, poly(ethylene glycol) (PEG) based anti-cancer drug conjugates will be discussed followed by a review of different types of PEG-b-poly(epsilon-caprolactone) (PEG-b-PCL) copolymer drug conjugates and histone deacetylase inhibitor polymer conjugates as novel therapeutics. The pH sensitive release of prodrugs will be discussed for polymer prodrug conjugates that are currently under investigation.