Design of liposomes containing photopolymerizable phospholipids for triggered release of contents

Abstract

We describe a novel class of light-triggerable liposomes prepared from a photo-polymerizable phospholipid DC8,9PC (1,2- bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine) and DPPC (1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine). Exposure to UV (254 nm) radiation for 0–45 minutes at 25°C resulted in photo-polymerization of DC8,9PC in these liposomes and the release of an encapsulated fluorescent dye (calcein). Kinetics and extents of calcein release correlated with mol% of DC8,9PC in the liposomes. Photopolymerization and calcein release occurred only from DPPC/DC8,9PC but not from Egg PC/DC8,9PC liposomes. Our data indicate that phase separation and packing of polymerizable lipids in the liposome bilayer are major determinants of photo-activation and triggered contents release.

Low-visibility light-intensity laser-triggered release of entrapped calcein from 1,2-bis (tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine liposomes is mediated through a type I photoactivation pathway

“…UV-triggered payload release from our photo-triggerable formulation is a consequence of DC 8,9 PC polymerization, 10,20 based on detection of photo-cross-linked DC 8,9 PC monomers 10,20 (accompanied by appearance of red and spectral shifts) and significant changes in the morphology of UV-treated liposomes (cryo-electron microscopy, unpublished observations). Surprisingly, we did not see any evidence of photo-cross-linking in 514 nm green laser-treated liposomes (formulation I), though Cal-G release was clearly evident (Figure 2).…”

“…14 The DPPC matrix lipid properties were found to play a critical role in the observed release of these two payloads. 20,10 By contrast, formulations that contained POPC (as the matrix lipid) with DC 8,9 PC ( Figure 1A) did not release the two payloads under identical light-exposure parameters. Liposomes containing DPPC as matrix lipids are referred to here as "photo-triggerable formulations," whereas liposomes containing POPC as matrix lipids are referred to as "nonphoto-triggerable formulations."…”

“…Liposomes that were selectively prepared from DPPC and DC 8,9 PC (formulation I, Table 1 and Figure 1A) were photo-triggerable. 10 Our formulated liposomes were found to release their payload (either calcein or doxorubicin) upon either an ultraviolet (UV) (254 nm) or to a green (514 nm) laser light exposure. 14 The DPPC matrix lipid properties were found to play a critical role in the observed release of these two payloads.…”

“…[1][2][3][4] Several studies have described the synthesis and properties of photoreactive molecules (primarily lipids) designed to enhance localized drug delivery (triggered release) upon activation by a suitable light source (photo-triggering). [5][6][7][8][9][10][11][12] Photo-triggering typically involves activation of the photosensitive molecules, causing a perturbation (destabilization) of the liposome membrane. 7,13,14 Release mechanisms of liposome-entrapped drugs and pharmaceuticals are generally based on localized membrane destabilization due to structural changes in fatty acid chains 5,7,11,15 (for further information on the mechanism[s] of photo-triggering of the lipid bilayers for enhanced drug delivery, readers are referred to comprehensive reviews).…”

“…Our liposome design also includes a polyethylene glycolated (PEGylated) lipid for future localized drug-delivery applications in cancer treatments. 10,14 The aqueous compartment of our formulated liposomes could be loaded with desired molecules of choice such as the photo-agent calcein or an anticancer agent such as doxorubicin. 14 The matrix lipid (such as DPPC) of choice was found to be important for lighttriggered release of payload content, as other investigated matrix lipids (such as egg PC or 1-palmitoyl-2-oleoyl phosphatidylcholine [POPC]) did not result in a photo-triggerable release (see Figure 1A).…”