Defense Date

3-17-2022

Graduation Date

Spring 5-21-2022

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Jelena M. Janjic

Committee Member

Jane Cavanaugh

Committee Member

Wilson Meng

Committee Member

James K. Drennen III

Committee Member

T. Kevin Hitchens

Keywords

perfluorocarbon nanoemulsion, quality by design, theranostic, multliple linear regression, near infrared fluorescence, 19F magnetic resonance imaging

Abstract

Nanocolloids are attractive delivery vehicles for drugs with poor aqueous solubility. Despite this, relatively few nanocolloid products exist on the market. Currently, there is a lack of standardization in the pre-clinical, academic setting regarding nanocolloid development and quality control testing. Adaptation of quality by design (QbD) methods used in the pharmaceutical industry to nanocolloid development is a desirable approach that can improve nanocolloid product and process understanding, resulting in an increased number of marketable products.

The central hypothesis of this work is that QbD approaches can be utilized to optimize theranostic (therapeutic and diagnostic) nanocolloid stability, drug loading, and imaging properties. The work presented here addresses this hypothesis through three primary aims. First, QbD approaches were used to develop scalable nanocolloids with optimal colloidal stability and drug loading. In the second aim, nanoemulsions with multimodal imaging capabilities were developed, and QbD approaches were employed to understand the parameters that impact the stability of the imaging reporters. With this knowledge, nanoemulsions with optimal therapeutic and diagnostic capabilities were developed and evaluated for their anti-inflammatory efficacy in the final aim of this work. This work demonstrates that QbD approaches aid in the development of high-quality theranostic nanocolloids. The approaches presented here can be adapted to the development and optimization of other nanomedicines.

Language

English

Additional Citations

Herneisey, M.; Lambert, E.; Kachel, A.; Shychuck, E.; Drennen, J. K., 3rd; Janjic, J. M., Quality by Design Approach Using Multiple Linear and Logistic Regression Modeling Enables Microemulsion Scale Up. Molecules 2019, 24 (11).

Herneisey, M.; Liu, L.; Lambert, E.; Schmitz, N.; Loftus, S.; Janjic, J. M., Development of Theranostic Perfluorocarbon Nanoemulsions as a Model Non-Opioid Pain Nanomedicine Using a Quality by Design (QbD) Approach. AAPS PharmSciTech 2019, 20 (2), 65.

Herneisey, M.; Williams, J.; Mirtic, J.; Liu, L.; Potdar, S.; Bagia, C.; Cavanaugh, J. E.; Janjic, J. M., Development and characterization of resveratrol nanoemulsions carrying dual-imaging agents. Ther Deliv 2016, 7 (12), 795-808.

Download

Share

COinS