Effect of Laser Irradiation on Reversibility and Drug Release of Light-Activatable Drug-Encapsulated Liposomes

Abstract

Although several studies have demonstrated repetitive drug release using light-activatable liposomes, inconsistent drug release at each activation limits widespread usage. Here, we report reversible plasmonic material-coated encapsulated liposomes for proportional controlled delivery of methotrexate (MTX), which is a common drug for cancer and autoimmune diseases, using repetitive laser irradiation. Our results suggest a proportional increase in total drug release after repetitive laser irradiation. We hypothesize that the drug is released via "melted" lipid bilayers when the plasmonic materials on the liposome surface are heated by laser irradiation followed by reversible formation of the liposome. To evaluate our hypothesis, the number density of liposomes after laser irradiation was measured using single-particle (liposome) collision experiments at an ultramicroelectrode. Collisional frequency data suggest that the number density of liposomes remains unaltered even after 60 s of laser irradiation at 1.1 and 1.8 W, indicating that the liposome structure is reversible. The results were further compared with gold nanorod-coated nanodroplets where drug is released via irreversible phase transition. In contrast to what was observed with the liposome particles, the number density of the nanodroplets decreased with increasing laser irradiation duration. The structure reversibility of our liposome particles may be responsible for repetitive drug release with laser heating. We also studied the temperature rise in the lipid bilayer by incorporating polymerized 10,12pentacosadiynoic acid (PCDA) in the lipid composition. The red shift in the UV−vis spectrum due to the structural change in PCDA lipids after laser irradiation indicates a rise in temperature above 75 °C, which is also above the chain-melting temperature of the main lipid used in the liposomes. All these results indicate that drug is released from the light-activatable liposomes due to reversible nanostructural alteration in the lipid bilayer by plasmonic resonance heating. The liposomes have potential to be a drug carrier for dose-controlled repetitive drug delivery.

Recent advances in single liposome electrochemistry

“…Although the blocking method is an efficient single collision technique for determining the frequency and the height of the current steps during the particle adsorption onto the UME surface [4,14,42,44,45], the reactor method brings more information on the mechanism of the electroporation process and the liposome content release [4,9,15,33,46]. The liposomes size distribution calculated from the charge passed in each current spike (by peak integration) in the i-t curve is a crucial information on the electrolysis process occurring upon impact onto the UME surface.…”

“…The liposomes size distribution calculated from the charge passed in each current spike (by peak integration) in the i-t curve is a crucial information on the electrolysis process occurring upon impact onto the UME surface. In this way, several recent investigations deal with the permeability of the liposomes lipid membrane and the effect of the membrane tension on the liposomes content release based on single impact events [9,15,44,46]. Especially, Zhang et al [9] have found that the liposomes electroporation process and the amount of released ferrocyanide content can be controlled by modifying the osmolarity of the buffer in which the 200 nm diameterliposomes are suspended.…”

Laser-Activated Drug Implant for Controlled Release to the Posterior Segment of the Eye

“…Our other previous study has also shown that in the longer laser duration, the more drug is released. 26 For the safety of the retina, we calculated maximum permissible exposure based on the following equation.…”

“…The laser used in this study was a pulsed picosecond laser with 700 ps pulse duration, 10 kHz repetition frequency at 1064 nm wavelength at 1 W. Although our previous study has shown that drug was released by a single pulse of this laser, 5 s was used per one spot to release physiologically relevant dose in this study. Our other previous study has also shown that in the longer laser duration, the more drug is released . For the safety of the retina, we calculated maximum permissible exposure based on the following equation …”

Design and Construction of pH-Selective Self-Lytic Liposome System

“…Cytosol has a physiological pH value around pH 7.4, whereas the endosome features a pH between 6.5 to 5.0 [10]. The release of the encapsulated contents from liposomes in response to light and temperature needs an additional outer device for their activation [11][12][13][14]. On the other hand, the pH-selective system needs no additional outer device.…”