Search Results (10)

Despite the appealing properties of random copolymers, the use of these biomaterials in association with phospholipids is still limited, as several aspects of their performance have not been investigated. The aim of this work is the formulation of lipid/random copolymer platforms and the comprehensive study of their features by multiple advanced characterization techniques. Both biomaterials are amphiphilic, including two phospholipids (1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)) and a statistical copolymer of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA). We examined the design parameters, including the lipid composition, the % comonomer ratio, and the lipid-to-polymer ratio that could be critical for their behavior. The structures were also probed in different conditions. To the best of the authors’ knowledge, this is the first time that P(OEGMA-co-DIPAEMA)/lipid hybrid colloidal dispersions have been investigated from a membrane mechanics, biophysical, and morphological perspective. Among other parameters, the copolymer architecture and the hydrophilic to hydrophobic balance are deemed fundamental parameters for the biomaterial co-assembly, having an impact on the membrane’s fluidity, morphology, and thermodynamics. Exploiting their unique characteristics, the most promising candidates were utilized for methotrexate (MTX) loading to explore their encapsulation capability and potential antitumor efficacy in vitro in various cell lines. Full article

Carotenoids are natural lipid-soluble pigments that produce yellow to red colors in plants as well as providing bright coloration in vegetables and fruits. Lutein belongs to the xanthophyll subgroup of the carotenoid family, which plays an essential role in photosynthesis and photoprotection in nature. In the human body, lutein, together with its isomer zeaxanthin and its metabolite meso-zeaxanthin, accumulates in the macula of the eye retina, which is responsible for central, high-resolution, and color vision. As a bioactive phytochemical, lutein has essential physiological functions, providing photoprotection against damaging blue light, along with the neutralization of oxidants and the preservation of the structural and functional integrity of cellular membranes. As a potent antioxidant and anti-inflammatory agent, lutein unfortunately has a low bioavailability because of its lipophilicity and a low stability as a result of its conjugated double bonds. In order to enhance lutein stability and bioavailability and achieve its controlled delivery to a target, nanoscale delivery systems, which have great potential for the delivery of bioactive compounds, are starting to be employed. The current review highlights the advantages and innovations associated with incorporating lutein within promising nanoscale delivery systems, such as liposomes, nanoemulsions, polymer nanoparticles, and polymer–lipid hybrid nanoparticles, as well as their unique physiochemical properties. Full article

Cell penetrating peptides (CPPs) are peptides that can directly adapt to cell membranes and then permeate into cells. CPPs are usually covalently linked to the surface of nanocarriers to endow their permeability to the whole system. However, hybrids with lipids or polymers make the metabolism much more sophisticated and even more difficult to determine. In this study, we present a continuous sequence of 18 amino acids (FFAARTMIWY(d-P)GAWYKRI). It forms nanospheres around 170 nm, which increase slightly after loading with siRNA and DOX. Notably, it can be internalized by cancer cells mainly through electronic interactions and PD-L1-mediated endocytosis. Compared with poly-l-lysine and polyethyleneimine, it has a much higher efficiency (about four times) of gene transduction while lowering toxicity. In the treatment of cancer, it causes apoptosis (21%) and inhibits the expression of SURVIVIN protein in vitro. In vivo, it shows good biocompatibility as there are no changes in mice’s body weight. When administering peptide-siRNA-DOX, tumor growth is inhibited the most (about three times). These results above prove the sequence to be a good candidate for gene therapy and drug delivery. Full article

Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation. Full article

Investigative systems for purified membrane transporters are almost exclusively reliant on the use of phospholipid vesicles or liposomes. Liposomes provide an environment to support protein function; however, they also have numerous drawbacks and should not be considered as a “one-size fits all” system. The use of artificial vesicles comprising block co-polymers (polymersomes) offers considerable advantages in terms of structural stability; provision of sufficient lateral pressure; and low passive permeability, which is a particular issue for transport assays using hydrophobic compounds. The present investigation demonstrates strategies to reconstitute ATP binding cassette (ABC) transporters into hybrid vesicles combining phospholipids and the block co-polymer poly (butadiene)-poly (ethylene oxide). Two efflux pumps were chosen; namely the Novosphingobium aromaticivorans Atm1 protein and human P-glycoprotein (Pgp). Polymersomes were generated with one of two lipid partners, either purified palmitoyl-oleoyl-phosphatidylcholine, or a mixture of crude E. coli lipid extract and cholesterol. Hybrid polymersomes were characterised for size, structural homogeneity, stability to detergents, and permeability. Two transporters, NaAtm1 and P-gp, were successfully reconstituted into pre-formed and surfactant-destabilised hybrid polymersomes using a detergent adsorption strategy. Reconstitution of both proteins was confirmed by density gradient centrifugation and the hybrid polymersomes supported substrate dependent ATPase activity of both transporters. The hybrid polymersomes also displayed low passive permeability to a fluorescent probe (calcein acetomethoxyl-ester (C-AM)) and offer the potential for quantitative measurements of transport activity for hydrophobic compounds. Full article

Biological membranes, in addition to being a cell boundary, can host a variety of proteins that are involved in different biological functions, including selective nutrient transport, signal transduction, inter- and intra-cellular communication, and cell-cell recognition. Due to their extreme complexity, there has been an increasing interest in developing model membrane systems of controlled properties based on combinations of polymers and different biomacromolecules, i.e., polymer-based hybrid films. In this review, we have highlighted recent advances in the development and applications of hybrid biomimetic planar systems based on different polymeric species. We have focused in particular on hybrid films based on (i) polyelectrolytes, (ii) polymer brushes, as well as (iii) tethers and cushions formed from synthetic polymers, and (iv) block copolymers and their combinations with biomacromolecules, such as lipids, proteins, enzymes, biopolymers, and chosen nanoparticles. In this respect, multiple approaches to the synthesis, characterization, and processing of such hybrid films have been presented. The review has further exemplified their bioengineering, biomedical, and environmental applications, in dependence on the composition and properties of the respective hybrids. We believed that this comprehensive review would be of interest to both the specialists in the field of biomimicry as well as persons entering the field. Full article

Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability. We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd₁₂-PEO₁₁ and PBd₂₂-PEO₁₄) mixed with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for the preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations. Full article

Hybrid membranes formed by co-assembly of A_xB_yA_x (hydrophilic-hydrophobic-hydrophilic) triblock copolymers into lipid bilayers are investigated by dissipative particle dynamics. Homogeneous hybrid membranes are developed as lipids and polymers are fully compatible. The polymer conformations can be simply classified into bridge- and loop-structures in the membranes. It is interesting to find that the long-time fraction of loop-conformation ( $f_L$ ) of copolymers in the membrane depends significantly on the hydrophilic block length (x). As x is small, an equilibrium $f_L^{*}$ always results irrespective of the initial conformation distribution and its value depends on the hydrophobic block length (y). For large x, $f_L$ tends to be time-invariant because polymers are kinetically trapped in their initial structures. Our findings reveal that only symmetric hybrid membranes are formed for small x, while membranes with stable asymmetric leaflets can be constructed with large x. The effects of block lengths on the polymer conformations, such as transverse and lateral spans ( $d^{\perp }$ and $d^{\Vert }$ ) of bridge- and loop-conformations, are discussed as well. Full article

Blending amphiphilic copolymers and lipids constitutes a novel approach to combine the advantages of polymersomes and liposomes into a new single hybrid membrane. Efforts have been made to design stimuli-responsive vesicles, in which the membrane’s dynamic is modulated by specific triggers. In this investigation, we proposed the design of pH-responsive hybrid vesicles formulated with poly(dimethylsiloxane)-block-poly(ethylene oxide) backbone (PDMS₃₆-b-PEO₂₃) and cationic switchable lipid (CSL). The latter undergoes a pH-triggered conformational change and induces membrane destabilization. Using confocal imaging and DLS measurements, we interrogated the structural changes in CSL-doped lipid and hybrid polymer/lipid unilamellar vesicles at the micro- and nanometric scale, respectively. Both switchable giant unilamellar lipid vesicles (GUV) and hybrid polymer/lipid unilamellar vesicles (GHUV) presented dynamic morphological changes, including protrusions and fission upon acidification. At the submicron scale, scattered intensity decreased for both switchable large unilamellar vesicles (LUV) and hybrid vesicles (LHUV) under acidic pH. Finally, monitoring the fluorescence leakage of encapsulated calcein, we attested that CSL increased the permeability of GUV and GHUV in a pH-specific fashion. Altogether, these results show that switchable lipids provide a pH-sensitive behavior to hybrid polymer/lipid vesicles that could be exploited for the triggered release of drugs, cell biomimicry studies, or as bioinspired micro/nanoreactors. Full article

In the emerging field of hybrid polymer/lipid vesicles, relatively few copolymers have been evaluated regarding their ability to form these structures and the resulting membrane properties have been scarcely studied. Here, we present the synthesis and self-assembly in solution of poly(dimethylsiloxane)-block-poly(ethylene oxide) diblock copolymers (PDMS-b-PEO). A library of different PDMS-b-PEO diblock copolymers was synthesized using ring-opening polymerization of hexamethylcyclotrisiloxane (D3) and further coupling with PEO chains via click chemistry. Self-assembly of the copolymers in water was studied using Dynamic Light Scattering (DLS), Static Light Scattering (SLS), Small Angle Neutron Scattering (SANS), and Cryo-Transmission Electron Microscopy (Cryo-TEM). Giant polymersomes obtained by electroformation present high toughness compared to those obtained from triblock copolymer in previous studies, for similar membrane thickness. Interestingly, these copolymers can be associated to phospholipids to form Giant Hybrid Unilamellar Vesicles (GHUV); preliminary investigations of their mechanical properties show that tough hybrid vesicles can be obtained. Full article