Amphiphilic And Random Copolymers: Self Assembly And Application In Drug Delivery Formulations
2019-03
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Amphiphilic And Random Copolymers: Self Assembly And Application In Drug Delivery Formulations
Authors
Published Date
2019-03
Publisher
Type
Thesis or Dissertation
Abstract
One of the biggest challenges in the field of drug delivery is the development of a system that can deliver cargo to a specific organ or cell and improve the aqueous solubility of poorly water soluble drugs. Recently, amphiphilic and random polymers have attracted considerable attention from researchers in order to elucidate these issues. Amphiphilic polymers consist of both hydrophilic and hydrophobic segments. Amphiphilic polymers are not only limited to drug delivery applications but also have utility in products such as food, detergents, paints, and cosmetics etc. Random copolymers consist of two or more monomers, the chain can add these monomers in any order. The incorporation on monomers into chain based on numerous factors such as conditions used for polymerization, reactivity of one monomer towards another etc. which can follow order depend on reactivity of one monomer towards another. Random polymers are continuously finding applications in the formulation industry due to their ability to improve aqueous solubility of poorly water soluble drugs. This thesis highlights my work on 1) the self-assembly of amphiphilic polymers to form micelles, 2) the application of micelles in pharmaceutical formulation, 3) the use of amphiphilic polymers as excipients, and 4) the use of random copolymers to enhance aqueous solubility of model drugs. Chapter 2 describes the synthesis of trehalose-containing amphiphilic diblock terpolymers with increasing trehalose content in the hydrophilic segment of the terpolymers. A poly(ethylene-alt-propylene)–poly[(N,N-dimethylacrylamide)-grad-poly(6-deoxy-6-methacrylamido trehalose)] (PEP-P(DMA-g-MAT)) polymer was chosen as a model system. The PEP content of the system was deliberately kept low to trigger formation of micelles in solution. PEP-P(DMA-g-MAT) successfully self-assembled into micelles in water. When incubated in various salt and serum-containing media, these micelles exhibited excellent stability from aggregation. Due to their excellent stability, these nanocarriers can be further optimized for potential systemic drug delivery applications. Chapter 3 demonstrates the effect of forming solution state polymer assemblies (prior to spray drying) on drug dissolution and supersaturation maintenance of poorly water soluble drugs. Herein, we synthesized four model polymer excipients (amphiphilic diblock ter- and copolymers): PEP-P(DMA-grad-MAG) and PEP-PDMA, and their respective hydrophilic analogues, P(DMA-grad-MAG) and PDMA. Our study clearly showed that formation of micelles prior to spray drying enhanced the dissolution of poorly water soluble drugs. Therefore, using micelle structures in excipient formulations is a simple and controlled platform for oral drug delivery. Chapter 4 describes a new synthetic platform with Trehalose-based diblock terpolymers to increase the solubility of poorly water soluble drug candidates. This study reveals that the solubility of polymer matrices in dissolution media and increase in hydrogen bonding sites in polymer matrices are critically important to decrease drug crystallinity & maintaining super saturation concentration in dissolution media. Chapter 5 presents the solubility enhancement of a highly lipophilic drug, phenytoin via interaction with poly(N-isopropylacrylamide-co-vinylpyrrolidone) (P(NIPAAm-co-VP)). Chapter 6 explains a systematic approach to understand structure-property relationships between drugs and excipients. This study illustrates that the first step to design a new excipient for a drug is to study the crystallization mechanism of that drug. When the drug crystallization mechanism is known, it is necessary to incorporate groups in the excipient formulation that can interact and interfere with the drug crystallization process to increase and maintain its aqueous solubility.
Keywords
Description
University of Minnesota Ph.D. dissertation.March 2019. Major: Chemistry. Advisor: Theresa Reineke. 1 computer file (PDF); ii, 217 pages.
Related to
Replaces
License
Collections
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Tale, Swapnil. (2019). Amphiphilic And Random Copolymers: Self Assembly And Application In Drug Delivery Formulations. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/215091.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.