Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: an Important Hydrophobic Nutraceutical
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University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses July 2020 Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: An Important Hydrophobic Nutraceutical Mahesh Kharat University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_2 Part of the Food Chemistry Commons Recommended Citation Kharat, Mahesh, "Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: An Important Hydrophobic Nutraceutical" (2020). Doctoral Dissertations. 1930. https://doi.org/10.7275/17372938 https://scholarworks.umass.edu/dissertations_2/1930 This Open Access Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. DESIGN AND FABRICATION OF COLLOIDAL DELIVERY SYSTEMS TO ENCAPSULATE AND PROTECT CURCUMIN: AN IMPORTANT HYDROPHOBIC NUTRACEUTICAL A Dissertation Presented by MAHESH M. KHARAT Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2020 Food Science © Copyright by Mahesh M. Kharat 2020 All Rights Reserved DESIGN AND FABRICATION OF COLLOIDAL DELIVERY SYSTEMS TO ENCAPSULATE AND PROTECT CURCUMIN: AN IMPORTANT HYDROPHOBIC NUTRACEUTICAL A Dissertation Presented by MAHESH M. KHARAT Approved as to style and content by: ____________________________________ David Julian McClements, Chair ____________________________________ Hang Xiao, Member ____________________________________ Zhenhua Liu, Member __________________________________ Eric Decker, Department Head Food Science To the greatest warrior, Arjuna who, in the middle of the battlefield, asked Lord Krishna this remarkable question- थितप्रज्ञथय का भाषा समाधिथिथय केशव | ||् प्रभाषेत ककमासीत व्रजेत ककम ﴂथितिी: कक भगव饍गीता अ鵍याय २, �लोक ५४ Sthita-prajnasya ka bhasa samadhi-sthasya kesava | Sthita-dhih kim prabhaseta kim asita vrajeta kim || Bhagavadgeeta Chapter 2, Verse 54 ACKNOWLEDGMENTS I would like to express my sincere gratitude to my advisor and mentor, Prof. Julian McClements, for his guidance and enormous support throughout my graduate studies. His efforts, knowledge, and encouragement have the greatest contribution to shaping my career as a young scientist. Every discussion I had with Julian was a stress reliever and an intellectual delight! I would like to thank my dissertation committee members, Dr. Hang Xiao and Dr. Zhenhua Liu. Their suggestions and feedback have greatly contributed to guiding my thesis work. I would like to thank Dr. Decker for the help and support in my research, teaching and co-curricular pursuits, and I am grateful for all of his assistance throughout my time at the University of Massachusetts. I would like to thank Fran, Mary, and Deby, for the help and coordination with the paperwork. A big thanks to Dave for assisting with activities in the pilot plant. I would also like to thank all of my past and current lab mates in the Biopolymers and Colloids Research Laboratory for their support, Anna, Bai, Cansu, Charmaine, Cheryl, Chengzhen, Feng, HaYoun, Irene, Jennie, Jorge, Jun, Kevin, Kubra, Li, Lu, Maria, Minqi, Nat, Ruyi, Sandra, Shelly, Sisie, Vanessa, Ye, Yeye, and Zach. It was a wonderful experience to be able to meet and share the workplace with people from around the world. I am indebted to Bing, and Tao for their love and care. I am grateful to Joy and Matt for their help in conducting and completing the lab work. I cannot adequately thank Jean Alamed for her support- my research work was not possible without her. Every time I entered Jean’s office with questions, concerns, and stress, I came out with answers, encouragement, and relief. I would like to thank all my friends. They continue to be a source of endless support and unconditional love. Their thoughts always keep my spirit bright. As I am writing this, I am thinking of my family, its struggle and sacrifices. Their thoughts, teachings, and values are the source of my integrity and wisdom. v ABSTRACT DESIGN AND FABRICATION OF COLLOIDAL DELIVERY SYSTEMS TO ENCAPSULATE AND PROTECT CURCUMIN: AN IMPORTANT HYDROPHOBIC NUTRACEUTICAL May 2020 MAHESH KHARAT, B.Tech., UNIVERSITY INSTITUTE OF CHEMICAL TEHNOLOGY MUMBAI M.Tech., INSTITUTE OF CHEMICAL TEHNOLOGY MUMBAI Ph.D., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Professor David Julian McClements Curcumin is a polyphenolic compound found in Turmeric (Curcuma longa) rhizome that has excellent biological benefits such as antioxidant, anti-inflammatory, and anti- cancer properties to name a few. However, its incorporation in food and pharmaceuticals is difficult due to low water solubility and chemical instability. This study focuses on developing colloidal delivery systems for efficient encapsulation and increased protection of curcumin for maximizing the proposed health benefits of curcumin. It was found that the physical and chemical stability of pure curcumin is impacted by pH, storage temperature, and molecular environment both in aqueous solutions and in oil- in-water emulsions. Pure curcumin was highly unstable to chemical degradation in neutral and alkaline aqueous solutions (pH ≥ 7.0) and it was most stable in acidic oil-in- water emulsions. Curcumin stability in emulsions depended on the emulsifier type, and the extent of curcumin degradation decreased in the following order: saponins > > gum arabic ≈ caseinate ≈ Tween 80. These results suggest that saponin accelerated curcumin degradation, which may be due to their ability to promote peroxidation reactions or it vi may be due to the presence of impurities in them, such as metals. The kinetics of curcumin degradation was significantly impacted by the mean droplet diameters (d32). The more rapid chemical degradation of the curcumin in the smaller droplets can be attributed to the fact that curcumin exchange between the interior and exterior of the droplets occurs more rapidly as the droplet dimensions decrease. Antioxidants were incorporated to protect curcumin in an emulsion having small droplets. The water-soluble antioxidants were more effective at protecting curcumin from degradation than the oil- soluble ones, which may have been because curcumin degrades faster in water than in oil, while the oil-soluble antioxidant actually slightly promoted curcumin degradation. Finally, the formation of nanostructured lipid carriers (NLCs) was optimized which, unlike O/W emulsion, consists of a solidified fat phase. NLCs were formulated using a hot-homogenization approach using fully hydrogenated soybean oil as the lipid phase and quillaja saponins as a natural surfactant. Characterization and stability studies revealed that NLCs have the potential to replace oil-in-water emulsions in commercial foods. Future studies are needed to establish their functional performance for curcumin encapsulation and protection. In summary, this study showed that the stability of curcumin in emulsions depends on various physicochemical parameters. This knowledge is important in designing and fabrication of colloidal systems for curcumin delivery. Keywords: Curcumin; emulsion; degradation, emulsifier type; droplet size; oil-water interfacial area; ascorbic acid; antioxidant; nanostructured lipid carrier vii TABLE OF CONTENTS Page ACKNOWLEDGMENTS ................................................................................................ v ABSTRACT .................................................................................................................. vi LIST OF TABLES .......................................................................................................... xii LIST OF FIGURES ....................................................................................................... xiii CHAPTER 1. LITERATURE REVIEW ............................................................................................. 1 1.1 Introduction ............................................................................................................ 1 1.2 Delivery by Design Approach ................................................................................ 2 1.2.1 Stage 1: Active agent definition ......................................................................... 3 1.2.1.1. Molecular and physicochemical characteristics.......................................... 3 1.2.1.1.1 Chemical formula and structure ........................................................ 3 1.2.1.1.2. Molar mass and density .................................................................... 4 1.2.1.1.3. Refractive index ............................................................................... 4 1.2.1.1.4. Melting and boiling properties ......................................................... 4 1.2.1.1.5. Partitioning ....................................................................................... 5 1.2.1.1.6. Diffusion coefficient ......................................................................... 5 1.2.1.1.7. Surface tension ................................................................................. 6 1.2.1.1.8. Solubility .......................................................................................... 6 1.2.1.1.9. Acid dissociation constants (pKa) ...................................................