The development of hyper-elastic liposomes

Large, Danielle

doi:10.17760/d20449632

Cited by 2 publications

(8 citation statements)

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“…= (245.0 ± 6.4) mN/m. Although we could not find K A results for DPMPC in the literature, the fact that both pure DOPC and DPMPC bilayers had statistically similar values of K A , is in qualitative agreement with the experimental observation that pure DOPC and DPMPC liposomes had statistically similar values of stretching moduli, as determined from micropipette aspiration measurements 27,28. For most compositions, DOPC and DPMPC bilayers mixed with DHPC or DDPC (Fig.4a) tend to have smaller values of 𝐾 !…”

supporting

confidence: 88%

“…The resulting liposomes had mean diameters ranging between 87-92 nm. Their results 27,28 indicate that the 75:25 liposomes were softer than their pure DOPC or DPMPC counterparts, with stretching moduli between 145-166 mN/m, as determined experimentally from micropipette aspiration. These values are 14-33% smaller than those obtained for pure DOPC (216 mN/m) or DPMPC (193 mN/m) liposomes.…”

Section: Introductionmentioning

confidence: 92%

“…In follow-up studies, Large et al 27,28 investigated other ways of developing highly elastic liposomes, by using formulations primarily composed of the unsaturated phospholipids 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 1,2-dipalmitoleoyl-sn-glycero-3phosphocholine (termed here DPMPC). These lipids had either 18 or 16 carbon atoms and a double bond linking carbon atoms 9 and 10 in both of their acyl tails.…”

Section: Introductionmentioning

confidence: 99%

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Understanding the Mechanical Properties of Ultra-Deformable Liposomes Using Molecular Dynamics Simulations

Xu,

Karra,

Large

et al. 2023

Preprint

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Improving drug delivery efficiency to solid tumor sites is a central challenge in anti-cancer therapeutic research. Our previous experimental study (Guo et al., Nat. Commun. 2018, 9, 130) showed that soft, elastic liposomes had increased uptake and accumulation in cancer cells and tumors in vitro and in vivo respectively, relative to rigid particles. As a first step towards understanding how liposomes’ molecular structure and composition modulates their elasticity, we performed all-atom and coarse-grained classical molecular dynamics (MD) simulations of lipid bilayers formed by mixing a long-tailed, unsaturated phospholipid with a short-tailed saturated lipid with the same head group. The former type of phospholipids considered were 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (termed here DPMPC). The shorter saturated lipids examined were 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC), 1,2-didecanoyl-sn-glycero-3-phosphocholine (DDPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Several lipid concentrations and surface tensions were considered. Our results show that DOPC or DPMPC systems having 25-35 mol% of the shortest lipids DHPC or DDPC are the least rigid, having area compressibility moduli KA that are ~10% smaller than the values observed in pure DOPC or DPMPC bilayers. These results agree with experimental measurements of the stretching modulus and lysis tension in liposomes with the same compositions. These systems also have lower areas per lipid, form more uneven x-y interfaces with water, the tails of both primary and secondary lipids are more disordered, and the terminal methyl groups in the tails of the long lipids DOPC or DPMPC wriggle more in the vertical direction, compared to pure DOPC or DPMPC bilayers or their mixtures with the longer saturated lipids DLPC or DMPC. These observations confirm our hypothesis that adding increasing concentrations of the short unsaturated lipids DHPC or DDPC to DOPC or DPMPC bilayers, alters lipid packing and thus make the resulting liposomes more elastic and less rigid. No formation of lipid nanodomains was noted in our simulations, and no clear trends were observed in the lateral diffusivities of the lipids as concentration, type of secondary lipid and surface tension were varied.

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supporting

confidence: 88%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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Understanding the Mechanical Properties of Ultra-Deformable Liposomes Using Molecular Dynamics Simulations

Xu,

Karra,

Large

et al. 2023

Preprint

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show abstract

“…The resulting liposomes had mean diameters ranging between 87 and 92 nm. Their results 27 , 28 indicate that the 75:25 liposomes were softer than their pure DOPC or DPMPC counterparts, with stretching moduli between 145 and 166 mN/m, as determined experimentally from micropipette aspiration. These values are 14–33% smaller than those obtained for pure DOPC (216 mN/m) or DPMPC (193 mN/m) liposomes.…”

Section: Introductionmentioning

confidence: 89%

“…In follow-up studies, Large et al , investigated other ways of developing highly elastic liposomes by using formulations primarily composed of the unsaturated phospholipid 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) or 1,2-dipalmitoleoyl- sn -glycero-3-phosphocholine (termed here DPMPC). These lipids had either 18 or 16 carbon atoms and a double bond linking carbon atoms 9 and 10 in both of their acyl tails.…”

Section: Introductionmentioning

confidence: 99%

Understanding the Mechanical Properties of Ultradeformable Liposomes Using Molecular Dynamics Simulations

Xu,

Karra,

Large

et al. 2023

J. Phys. Chem. B

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Improving drug delivery efficiency to solid tumor sites is a central challenge in anticancer therapeutic research. Our previous experimental study (Guo et al., Nat. Commun. 2018, 9, 130) showed that soft, elastic liposomes had increased uptake and accumulation in cancer cells and tumors in vitro and in vivo respectively, relative to rigid particles. As a first step toward understanding how liposomes' molecular structure and composition modulates their elasticity, we performed all-atom and coarsegrained classical molecular dynamics (MD) simulations of lipid bilayers formed by mixing a long-tailed unsaturated phospholipid with a short-tailed saturated lipid with the same headgroup. The former types of phospholipids considered were 1,2-dioleoyl-snglycero-3-phosphocholine (DOPC) and 1,2-dipalmitoleoyl-sn-glycero-3-phosphocholine (termed here DPMPC). The shorter saturated lipids examined were 1,2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC), 1,2-didecanoyl-sn-glycero-3-phosphocholine (DDPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Several lipid concentrations and surface tensions were considered. Our results show that DOPC or DPMPC systems having 25−35 mol % of the shortest lipids DHPC or DDPC are the least rigid, having area compressibility moduli K A that are ∼10% smaller than the values observed in pure DOPC or DPMPC bilayers. These results agree with experimental measurements of the stretching modulus and lysis tension in liposomes with the same compositions. These mixed systems also have lower areas per lipid and form more uneven x−y interfaces with water, the tails of both primary and secondary lipids are more disordered, and the terminal methyl groups in the tails of the long lipid DOPC or DPMPC wriggle more in the vertical direction, compared to pure DOPC or DPMPC bilayers or their mixtures with the longer saturated lipid DLPC or DMPC. These observations confirm our hypothesis that adding increasing concentrations of the short unsaturated lipid DHPC or DDPC to DOPC or DPMPC bilayers alters lipid packing and thus makes the resulting liposomes more elastic and less rigid. No formation of lipid nanodomains was noted in our simulations, and no clear trends were observed in the lateral diffusivities of the lipids as the concentration, type of secondary lipid, and surface tension were varied.

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The development of hyper-elastic liposomes

Cited by 2 publications

References 0 publications

Understanding the Mechanical Properties of Ultra-Deformable Liposomes Using Molecular Dynamics Simulations

Understanding the Mechanical Properties of Ultra-Deformable Liposomes Using Molecular Dynamics Simulations

Understanding the Mechanical Properties of Ultradeformable Liposomes Using Molecular Dynamics Simulations

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