Enhancing oral delivery of plant-derived vesicles for colitis

Yuan Liu; Adrian Lankenau Ahumada; Emine Bayraktar; Paul Schwartz; Mamur Chowdhury; Sixiang Shi; Manu M Sebastian; Htet Khant; Natalia de Val; Nazende Nur Bayram; Guodong Zhang; Thanh Chung Vu; Zuliang Jie; Nicholas B Jennings; Cristian Rodriguez-Aguayo; Jody Swain; Elaine Stur; Lingegowda S Mangala; Yutuan Wu; Supriya Nagaraju; Brooke Ermias; Chun Li; Gabriel Lopez-Berestein; Janet Braam; Anil K Sood

doi:10.1016/j.jconrel.2023.03.056

Enhancing oral delivery of plant-derived vesicles for colitis

J Control Release. 2023 May:357:472-483. doi: 10.1016/j.jconrel.2023.03.056. Epub 2023 Apr 20.

Authors

Yuan Liu¹, Adrian Lankenau Ahumada², Emine Bayraktar³, Paul Schwartz⁴, Mamur Chowdhury⁵, Sixiang Shi⁶, Manu M Sebastian⁷, Htet Khant⁸, Natalia de Val⁹, Nazende Nur Bayram¹⁰, Guodong Zhang¹¹, Thanh Chung Vu¹², Zuliang Jie¹³, Nicholas B Jennings¹⁴, Cristian Rodriguez-Aguayo¹⁵, Jody Swain¹⁶, Elaine Stur¹⁷, Lingegowda S Mangala¹⁸, Yutuan Wu⁶, Supriya Nagaraju¹⁹, Brooke Ermias²⁰, Chun Li²¹, Gabriel Lopez-Berestein²², Janet Braam²³, Anil K Sood²⁴

Affiliations

¹ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of BioSciences, Rice University, Houston, TX 77005, USA. Electronic address: yliu32@mdanderson.org.
² Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of BioSciences, Rice University, Houston, TX 77005, USA. Electronic address: ALankenau@mdanderson.org.
³ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: EBayraktar@mdanderson.org.
⁴ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: Paul.Schwartz@tufts.edu.
⁵ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: mamur@utexas.edu.
⁶ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁷ Department of Veterinary Medicine and Surgery, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: MMSebastian@mdanderson.org.
⁸ Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Inc., Frederick, MD 21702, USA. Electronic address: htet.khant@nih.gov.
⁹ Center for Molecular Microscopy, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Inc., Frederick, MD 21702, USA. Electronic address: natalia.deval@thermofisher.com.
¹⁰ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: NNBayram@mdanderson.org.
¹¹ Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: GZhang3@mdanderson.org.
¹² Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: TVu9@mdanderson.org.
¹³ Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jiezuliang@xmu.edu.cn.
¹⁴ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: nbjennin@mdanderson.org.
¹⁵ Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: CRodriguez2@mdanderson.org.
¹⁶ Department of Veterinary Medicine and Surgery, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: JSwain@mdanderson.org.
¹⁷ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: EStur@mdanderson.org.
¹⁸ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: lsmangala@mdanderson.org.
¹⁹ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: SNagaraju@mdanderson.org.
²⁰ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: be13@rice.edu.
²¹ Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: CLi@mdanderson.org.
²² Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: glopez@mdanderson.org.
²³ Department of BioSciences, Rice University, Houston, TX 77005, USA. Electronic address: Braam@rice.edu.
²⁴ Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: asood@mdanderson.org.

Abstract

Plant-derived vesicles (PDVs) are attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs did not have an appreciable impact on PDV structure, number, or therapeutic effect. Additionally, packaging the lyophilized Eudragit S100-coated PDVs into capsules allowed them to pass through the upper gastrointestinal tract for delivery into the colon better than did suspension of PDVs in phosphate-buffered saline. Cap-cPDVs showed robust therapeutic effect in a dextran sulfate sodium-induced colitis mouse model. These findings could have broad implications for the use of PDVs as orally delivered nanocarriers of natural therapeutic plant compounds or other therapeutics.

Keywords: Eudragit S100 coat; Gastrointestinal tract; Lyophilization; Oral delivery; Plant-derived vesicles; Vesicle stability.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Colitis* / chemically induced
Colitis* / drug therapy
Drug Delivery Systems
Hydrogen-Ion Concentration
Mice
Polymethacrylic Acids / chemistry

Substances

methylmethacrylate-methacrylic acid copolymer
Polymethacrylic Acids

Abstract

Publication types

MeSH terms

Substances

Grants and funding