Structural Characterization of Photopolymerizable Binary Liposomes Containing Diacetylenic and Saturated Phospholipids

Abstract

The use of liposomes to encapsulate materials has received widespread attention for drug delivery, transfection, diagnostic reagent, and as immunoadjuvants. Phospholipid polymers form a new class of biomaterials with many potential applications in medicine and research. Of interest are polymeric phospholipids containing a diacetylene moiety along their acyl chain since these kinds of lipids can be polymerized by Ultra-Violet (UV) irradiation to form chains of covalently linked lipids in the bilayer. In particular the diacetylenic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer. As knowledge of liposome structures is certainly fundamental for system design improvement for new and better applications, this work focuses on the structural properties of polymerized DC8,9PC:1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes. Liposomes containing mixtures of DC8,9PC and DMPC, at different molar ratios, and exposed to different polymerization cycles, were studied through the analysis of the electron spin resonance (ESR) spectra of a spin label incorporated into the bilayer, and the calorimetric data obtained from differential scanning calorimetry (DSC) studies. Upon irradiation, if all lipids had been polymerized, no gel-fluid transition would be expected. However, even samples that went through 20 cycles of UV irradiation presented a DSC band, showing that around 80% of the DC8,9PC molecules were not polymerized. Both DSC and ESR indicated that the two different lipids scarcely mix at low temperatures, however few molecules of DMPC are present in DC8,9PC rich domains and vice versa. UV irradiation was found to affect the gel-fluid transition of both DMPC and DC8,9PC rich regions, indicating the presence of polymeric units of DC8,9PC in both areas. A model explaining lipids rearrangement is proposed for this partially polymerized system.

Potentiating antilymphoma efficacy of chemotherapy using a liposome for integration of CD20 targeting, ultra-violet irradiation polymerizing, and controlled drug delivery

“…Then, the solvent was evaporated under vortex and flashed with nitrogen to obtain the lipid film, followed by washing-out with 2 mL of ADR (doxorubicin HCl, Melonepharma CO. LTD., Dalian, China) solution (0.5 mg/mL in PBS) to obtain ADR-loaded multilamellar vesicles [26]. The collected liposome solution was dialyzed against PBS using a membrane (molecular weight cutoff 3 kDa) at 4°C for 12 h to remove uncombined ADR resulting in the ADR-loaded liposome stocking solutions.…”

“…The BSA-conjugated liposome was fabricated in the same way. For UV irradiation, pure liposome solutions were exposed to 20 irradiation cycles at 4°C, with a 254-nm UV light dose of 360 mJ/cm 2 per cycle using a Stratalinker-UV 1800 [26]. The concentration of Fab fragments in the liposome solution was quantified by measuring the A260/A280 using Nano VueTM (GE Healthcare, Wilmington, MA, USA).…”

“…In this study, we have developed an adriamycin (ADR)-loaded liposome using the diacetylenic phosphatidylcholine 1,2-bis(10,12-tricosadiynoyl)-sn-glycero-3-phosphocholine (DC8,9PC, hereafter referred to as PC), which can form intermolecular cross-linking through the diacetylenic group to produce a conjugated polymer within the hydrocarbon region of the bilayer by ultra-violet (UV) irradiation (Additional file 1: Figure S1) [26,27]. For the sake of active targeting, the Fab fragments of rituximab were conjugated onto the liposomal surface.…”

Relation between biophysical properties of nanostructures and their toxicity on zebrafish

“…(Temprana et al 2010) demonstrated that the polymerization efficiency of DC8,9PC and 1,2-dimirystoil-sn-glycero-3-phosphocholine (DMPC) in a [1:1] molar ratio is higher than that obtained when the molar ratio is [1:0.5] or [1:0.25]. In these mixtures, only DC8,9PC is polymerizable, so in irradiated bilayers there is a coexistence of large unpolymerized regions with polymerized domains, as shown in Fig.…”

“…The authors proposed that the combination between lipopolymers and L-arginine results in a metabolic activation Fig. 4 Proposed model for lipopolymers formed with 1,2-bis (10,12-tricosadinoyl)-sn-glycero-3-phosphocholine (DC8,9PC) and 1,2-dimirystoil-sn-glycero-3-phosphocholine (DMPC) in a 1:1 M ratio (Temprana et al 2010) that is not induced by any of the two components independently (Fernandez Ruocco 2011).…”