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Understanding Repetitive Drug Release of Laser-Activatable Drug Carriers

Yuan, Zheng
http://orcid.org/0000-0002-2368-0315
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637154213089625

Abstract Details

2021, PhD, University of Cincinnati, Engineering and Applied Science: Chemical Engineering.
The complex structure of the eye and the blood-ocular barriers have impeded the drug delivery via conventional administration routes. Innovative on-demand drug delivery system targeted to the eye has been considered as a promising strategy and received great attention in recent years. Hence, we investigated drug nanocarriers which can be activated by near infrared (NIR) laser to release the payload in a controlled manner over a long period.
We first evaluated gold nanorod (AuNR)-coated perfluorocarbon (PFC) nanodroplets with two different PFC cores, perfluoropentane (C5F12, PF5) and perfluorohexane (C6F14, PF6). These PFC nanodroplets undergo a liquid-to-gas phase-transition and “burst” to release the payload with NIR laser. The size, encapsulation efficiency, number density, and cytotoxicity were similar between PF5 and PF6 nanodroplets. The feasibility of both PF5 and PF6 nanodroplets on suppressing the in vitro angiogenesis was demonstrated. PF6 nanodroplets performed better in long-term stability at physiological conditions but showed lower phase-transition efficiency than PF5.
Subsequently, AuNR-coated nanosized liposomes (diameter˜100 nm) were studied with a focus on structure reversibility. Laser-triggered drug release tests demonstrated that these AuNR-liposomes released drug repetitively with multiple irradiation cycles (5sec per cycle, 1.1W) and the released amounts were proportional to cycle numbers. It was also proved that AuNR prominently increased the temperature of lipid bilayers via plasmonic heating effect and facilitated drug-releasing when irradiated by NIR laser. In addition, the number density of liposomes remained the same after laser irradiation. These results implied that the structures of AuNR-liposomes are likely to be reversible after exposure to NIR laser. Next, we fabricated micron-sized (diameter˜1.5 µm) AuNR-liposomes by reverse-phase evaporation method. Similarly, these micron-sized liposomes showed repetitive drug releases with multiple laser cycles. Long-term stability was monitored, showing that these liposomes were relatively stable against aggregation or passive leakage over 5 months. Furthermore, the micron-sized AuNR-liposomes were loaded to a nanoporous polymeric implant and injected to rabbit eyes for in vivo evaluation.
Further research was conducted to study the effect of cholesterol on the nanostructural alteration of liposomes upon laser irradiation. AuNR-coated liposomes containing 35 mol% cholesterol (+Chol+Au) showed significant higher concentration of released drug at multiple laser cycles, compared to cholesterol-free (−Chol+Au) liposomes. Meanwhile, the formation of aggregates or fused +Chol+Au liposomes after 5sec or 20sec laser irradiation has been detected by EQ-SANS and TEM. However, DLS didn’t show size increase after laser. Thus, it is suspected that only partial liposomes aggregated during the laser irradiation. Further experiments are needed to find out the mechanisms that be responsible for the differences.
Yoonjee Park, Ph.D. (Committee Chair)
Jonathan Nickels (Committee Member)
Winston Kao, Ph.D. (Committee Member)
Gregory Beaucage, Ph.D. (Committee Member)
153 p.
Chemical Engineering
drug delivery; light-activatable drug delivery; liposome structure; Surface plasmonic resonance; repetitive drug release

Recommended Citations

Citations

  • Yuan, Z. (2021). Understanding Repetitive Drug Release of Laser-Activatable Drug Carriers [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637154213089625

    APA Style (7th edition)

  • Yuan, Zheng. Understanding Repetitive Drug Release of Laser-Activatable Drug Carriers. 2021. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637154213089625.

    MLA Style (8th edition)

  • Yuan, Zheng. "Understanding Repetitive Drug Release of Laser-Activatable Drug Carriers." Doctoral dissertation, University of Cincinnati, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1637154213089625

    Chicago Manual of Style (17th edition)

ucin1637154213089625
57
© 2021, some rights reserved.Creative Commons License Understanding Repetitive Drug Release of Laser-Activatable Drug Carriers by Zheng Yuan is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.