Cubosomes stabilized by a polyphosphoester-analog of Pluronic F127 with reduced cytotoxicity

Fornasier, Marco; Biffi, Stefania; Bortot, Barbara; Macor, Paolo; Manhart, Angelika; Wurm, Frederik R.; Murgia, Sergio

doi:10.1016/j.jcis.2020.07.038

Cited by 59 publications

(42 citation statements)

References 47 publications

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“…[372] ★ ★ Lower complement activation compared to PEG reported. [382] Comparable opsonization and macrophage uptake. [372] Poor or no data on blood circulation, ABC phenomenon…”

Section: Bioinert Protein Binding Stealthmentioning

confidence: 99%

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Friedl

Nele

Rosa

et al. 2021

Adv Funct Materials

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Nanocarriers (NCs) have emerged as powerful tools to improve drug solubility, to promote drug transport across membranes, to protect their payload from premature degradation, and to deliver drugs in a controlled and targeted manner. Their performance strongly depends on the surface chemistry, which governs their interaction with the biological environment. Bioinert and stealth surface features are advantageous to avoid unintended interactions with endogenous surfaces at off‐target sites and with the immune system, whereas at the target site these carriers should be highly interactive guaranteeing intracellular delivery of their payload. These key surface properties—bioinert and stealth versus interactive at the target site—are in contradiction to each other so that the best compromise between them has to be found. Alternatively, surface structures interacting preferentially with the membrane of target cells can be utilized. Stimuli‐responsive surfaces able to convert from bioinert and stealth to interactive at the target site have been recently introduced. A deepened understanding of how these different approaches influence the performance of NCs in the body is of particular importance in order to improve their efficacy. This review focuses on the surface chemistry of NCs providing the best compromise between bioinert and stealth versus interactive features.

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“…[372] ★ ★ Lower complement activation compared to PEG reported. [382] Comparable opsonization and macrophage uptake. [372] Poor or no data on blood circulation, ABC phenomenon…”

Section: Bioinert Protein Binding Stealthmentioning

confidence: 99%

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Friedl

Nele

Rosa

et al. 2021

Adv Funct Materials

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“…Lower cytotoxicity compared to the commonly used Pluronic F127 analogues was detected. 16 A systematic blood compatibility study of different PPEs has not been reported to date. Here, we report the hemocompatibility of a set of PPEs with various molar masses and different hydrophilicities, as well as PPE-coated model nanocarriers.…”

Section: Introductionmentioning

confidence: 99%

Blood Compatibility of Hydrophilic Polyphosphoesters

Pelosi

Constantinescu

Son

et al. 2022

ACS Appl. Bio Mater.

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Polyphosphoesters (PPEs) are a class of versatile degradable polymers. Despite the high potential of this class of polymers in biomedical applications, little is known about their blood interaction and compatibility. We evaluated the hemocompatibility of water-soluble PPEs (with different hydrophilicities and molar masses) and PPE-coated model nanocarriers. Overall, we identified high hemocompatibility of PPEs, comparable to poly(ethylene glycol) (PEG), currently used for many applications in nanomedicine. Hydrophilic PPEs caused no significant changes in blood coagulation, negligible platelet activation, the absence of red blood cells lysis, or aggregation. However, when a more hydrophobic copolymer was studied, some changes in the whole blood clot strength at the highest concentration were detected, but only concentrations above that are typically used for biomedical applications. Also, the PPE-coated model nanocarriers showed high hemocompatibility. These results contribute to defining hydrophilic PPEs as a promising platform for degradable and biocompatible materials in the biomedical field.

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“…There have been a number of studies on alternative polymers to substitute for Pluronic polymers for preparing LLC lipid nanoparticles, and a range of synthetic and commercially available polymers [49], including amphiphilic brush copolymers [50,51], poly(ethylene glycol) (PEG)-conjugated lipids [51][52][53] and amphiphilic proteins [54], have been explored. Numerous studies have shown that the choice of steric stabilizer not only can influence the particle size, size distribution and the internal mesophase of the formed lipid nanoparticles [49,55], but can have benefits of reducing cytotoxicity profile [56,57] and manipulating complement response [52].…”

Section: Introductionmentioning

confidence: 99%

Novel Amphiphilic Block Copolymers for the Formation of Stimuli-Responsive Non-Lamellar Lipid Nanoparticles

et al. 2021

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Non-lamellar lyotropic liquid crystalline (LLC) lipid nanoparticles contain internal multidimensional nanostructures such as the inverse bicontinuous cubic and the inverse hexagonal mesophases, which can respond to external stimuli and have the potential of controlling drug release. To date, the internal LLC mesophase responsiveness of these lipid nanoparticles is largely achieved by adding ionizable small molecules to the parent lipid such as monoolein (MO), the mixture of which is then dispersed into nanoparticle suspensions by commercially available poly(ethylene oxide)–poly(propylene oxide) block copolymers. In this study, the Reversible Addition-Fragmentation chain Transfer (RAFT) technique was used to synthesize a series of novel amphiphilic block copolymers (ABCs) containing a hydrophilic poly(ethylene glycol) (PEG) block, a hydrophobic block and one or two responsive blocks, i.e., poly(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate) (PTBA) and/or poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA). High throughput small angle X-ray scattering studies demonstrated that the synthesized ABCs could simultaneously stabilize a range of LLC MO nanoparticles (vesicles, cubosomes, hexosomes, inverse micelles) and provide internal particle nanostructure responsiveness to changes of hydrogen peroxide (H2O2) concentrations, pH and temperature. It was found that the novel functional ABCs can substitute for the commercial polymer stabilizer and the ionizable additive in the formation of next generation non-lamellar lipid nanoparticles. These novel formulations have the potential to control drug release in the tumor microenvironment with endogenous H2O2 and acidic pH conditions.

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Cubosomes stabilized by a polyphosphoester-analog of Pluronic F127 with reduced cytotoxicity

Cited by 59 publications

References 47 publications

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Bioinert, Stealth or Interactive: How Surface Chemistry of Nanocarriers Determines Their Fate In Vivo

Blood Compatibility of Hydrophilic Polyphosphoesters

Novel Amphiphilic Block Copolymers for the Formation of Stimuli-Responsive Non-Lamellar Lipid Nanoparticles

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