Understanding cochleate formation: insights into structural development

Nagarsekar, Kalpa; Ashtikar, Mukul; Steiniger, Frank; Thamm, Jana; Schacher, Felix H.; Fahr, Alfred

doi:10.1039/c5sm01469g

Cited by 24 publications

(25 citation statements)

References 45 publications

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“…Cochleates have attrached attention as promising drug delivery vehicles due to the possibility of incorporating a wide range of molecules into the rolls. Electron microscopy and theoretical modeling have been employed to understand the conditions for formation of cochleates 53 , 54 . We do not observe rolling without the addition of annexins in our system because both membrane monolayers are exposed equally to Ca 2+ .…”

Section: Discussionmentioning

confidence: 99%

Annexins induce curvature on free-edge membranes displaying distinct morphologies

Boye

Jeppesen

Maeda

et al. 2018

Sci Rep

121

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Annexins are a family of proteins characterized by their ability to bind anionic membranes in response to Ca2+-activation. They are involved in a multitude of cellular functions including vesiculation and membrane repair. Here, we investigate the effect of nine annexins (ANXA1-ANXA7, ANXA11, ANXA13) on negatively charged double supported membrane patches with free edges. We find that annexin members can be classified according to the membrane morphology they induce and matching a dendrogam of the annexin family based on full amino acid sequences. ANXA1 and ANXA2 induce membrane folding and blebbing initiated from membrane structural defects inside patches while ANXA6 induces membrane folding originating both from defects and from the membrane edges. ANXA4 and ANXA5 induce cooperative roll-up of the membrane starting from free edges, producing large rolls. In contrast, ANXA3 and ANXA13 roll the membrane in a fragmented manner producing multiple thin rolls. In addition to rolling, ANXA7 and ANXA11 are characterized by their ability to form fluid lenses localized between the membrane leaflets. A shared feature necessary for generating these morphologies is the ability to induce membrane curvature on free edged anionic membranes. Consequently, induction of membrane curvature may be a significant property of the annexin protein family that is important for their function.

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Section: Discussionmentioning

confidence: 99%

Annexins induce curvature on free-edge membranes displaying distinct morphologies

Boye

Jeppesen

Maeda

et al. 2018

Sci Rep

121

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“…Nanocochleates are stable phospholipid-cation precipitates with multilayered cylindrical structures, composed of positively charged calcium ions and negatively charged phospholipid 5 . When drugs are incorporated into nanocochleates, the unique multilayered cylindrical structures provide protection from drug degradation in hazardous environmental conditions, resulting in enhanced oral bioavailability 6 7 .…”

mentioning

confidence: 99%

Chitosan functionalized nanocochleates for enhanced oral absorption of cyclosporine A

Liu

Zhong

Yang

2017

Sci Rep

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It remains a significant challenge to overcome the poor permeability of cyclosporine A and enhance its oral absorption. In this study, we have identified a positively charged chitosan that is able to induce coiling up of anionic lipids to form nanocochleates with an average size of 114.2 ± 0.8 nm, without the need for calcium ions. These functional chitosan-induced nanocochleates enhanced gastrointestinal absorption of cyclosporine A, up to a 3-fold increase in oral bioavailability. A fluorescence-labeling study confirmed that absorption mainly occurred in the duodenum and jejunum. Transport studies indicated that uptake of chitosan-induced nanocochleates by Caco-2 cells was by clathrin- and caveolae-mediated endocytosis, but not by macropinocytosis. Furthermore, three cellular tight junction proteins, ZO-1, F-actin and claudin-4, were significantly down-regulated, suggesting that chitobiose-induced nanocochleates are able to reconstruct and open tight junctions in intestinal epithelial cells to enhance drug absorption. In summary, these novel bifunctional chitosan-induced nanocochleates appear to have potential to facilitate oral delivery of cyclosporine A.

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“…Negatively charged phospholipids could be also used to form so-called cochleates, defined as supramolecular assemblies of phospholipid bilayers which form spiral structures with divalent cations [82]. Despite the thorough characterization conducted by Fahr and coworkers so far [83,84], their clinical potential regarding their use as drug delivery system still needs to be investigated.…”

Section: Liposomal Systemsmentioning

confidence: 99%

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

Rahnfeld

Luciani

2020

Pharmaceutics

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The remarkable number of new molecular entities approved per year as parenteral drugs, such as biologics and complex active pharmaceutical ingredients, calls for innovative and tunable drug delivery systems. Besides making these classes of drugs available in the body, injectable depot formulations offer the unique advantage in the parenteral world of reducing the number of required injections, thus increasing effectiveness as well as patient compliance. To date, a plethora of excipients has been proposed to formulate depot systems, and among those, lipids stand out due to their unique biocompatibility properties and safety profile. Looking at the several long-acting drug delivery systems based on lipids designed so far, a legitimate question may arise: How far away are we from an ideal depot formulation? Here, we review sustained release lipid-based platforms developed in the last 5 years, namely oil-based solutions, liposomal systems, in situ forming systems, solid particles, and implants, and we critically discuss the requirements for an ideal depot formulation with respect to the used excipients, biocompatibility, and the challenges presented by the manufacturing process. Finally, we delve into lights and shadows originating from the current setups of in vitro release assays developed with the aim of assessing the translational potential of depot injectables.

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Understanding cochleate formation: insights into structural development

Cited by 24 publications

References 45 publications

Annexins induce curvature on free-edge membranes displaying distinct morphologies

Annexins induce curvature on free-edge membranes displaying distinct morphologies

Chitosan functionalized nanocochleates for enhanced oral absorption of cyclosporine A

Injectable Lipid-Based Depot Formulations: Where Do We Stand?

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