Poly Glycerol Research Articles

Polyamidoamine and polyglycerol; their linear, dendritic and linear-dendritic architectures as anticancer drug delivery systems.

Despite extensive investigations in the field of cancer diagnosis and therapy in recent decades, cancer is still the major cause of morbidity and mortality all over the world. Recently, with the advancement of nanotechnology, the design and preparation of efficient nano-sized structures with the potential for diagnosis and treatment of cancer have been proposed. Among the different types of nano-sized materials, biocompatible polymers seem to be innovative tools with huge potential for cancer treatment. Advances in polymer chemistry and the application of various organic reactions have enabled the design and tailoring of multifunctional polymeric platforms with controllable architectures, with the ability to carry anticancer drugs, labelling probes and targeting agents simultaneously. This review covers the latest advances in the conjugation of the most studied chemotherapeutics (such as doxorubicin, paclitaxel, methotrexate, fluorouracil and cisplatin) to common dendritic polymers, including polyamidoamine dendrimers and hyperbranched polyglycerols (PGs) and their linear analogues, producing fatal weapons against tumors, with a focus on their cytotoxicity, biodistribution and biodegradability.

Fabrication and characterization of biodegradable polymeric films as a corneal stroma substitute.

Background:Biodegradable elastomeric materials such as poly glycerol sebacate (PGS) have gained much current attention in the field of soft tissue engineering. The present study reports the synthesis of PGS with molar ratios of 1:1, 2:3, and 3:2 of glycerol and sebacic acid via polycondensation reaction and tests the effect of PGS on human corneal epithelial (HCE) cells viability in vitro.Materials and Methods:PGS films were prepared by the casting method. We tried to fabricate PGS with different compositions and various properties as being a viable alternative to the corneal stroma in cornea tissue engineering. The chemical properties of the prepared polymer were investigated by means of attenuated total reflectance – Fourier transform infrared spectroscopy (ATR-FTIR) analysis and the in vitro cytotoxicity was investigated by the Alamarblue method.Results:The functional groups observed in the PGS FTIR spectrums of PGS with various molar ratios were the same. However, the main difference was the time of completing the cross-linking reaction. The PGS prepared by 2:3 ratio as a molar ratio had the fastest and the 3:2 ratio had the lowest cross-linking rate because of the higher amount of sebacic acid. Results of the Alamarblue cytotoxicity test assay showed no deleterious effect on HCE cell viability and proliferation.Conclusions:PGS is a potentially good candidate material for corneal tissue engineering because of its lack of in vitro HCE cell toxicity.

Highly efficient hyperbranched CNT surfactants: influence of molar mass and functionalization.

End-group-functionalized hyperbranched polymers were synthesized to act as a carbon nanotube (CNT) surfactant in aqueous solutions. Variation of the percentage of triphenylmethyl (trityl) functionalization and of the molar mass of the hyperbranched polyglycerol (PG) core resulted in the highest measured surfactant efficiency for a 5000 g/mol PG with 5.6% of the available hydroxyl end-groups replaced by trityl functions, as shown by UV-vis measurements. Semiempirical model calculations suggest an even higher efficiency for PG5000 with 2.5% functionalization and maximal molecule specific efficiency in general at low degrees of functionalization. Addition of trityl groups increases the surfactant-nanotube interactions in comparison to unfunctionalized PG because of π-π stacking interactions. However, at higher functionalization degrees mutual interactions between trityl groups come into play, decreasing the surfactant efficiency, while lack of water solubility becomes an issue at very high functionalization degrees. Low molar mass surfactants are less efficient compared to higher molar mass species most likely because the higher bulkiness of the latter allows for a better CNT separation and stabilization. The most efficient surfactant studied allowed dispersing 2.85 mg of CNT in 20 mL with as little as 1 mg of surfactant. These dispersions, remaining stable for at least 2 months, were mainly composed of individual CNTs as revealed by electron microscopy.

Abstract 4391: Multi-modal nanomedicine for glioblastoma

Abstract Glioblastoma multiforme (GBM) is an aggressive primary neoplasm of the brain that exhibit notable refractivity to standard treatment regimens. Recent large-scale molecular profiling has revealed deregulated molecular networks as potential targets for therapeutic development. MicroRNAs (miRNAs) are noncoding RNA molecules which act as post-transcriptional regulators of specific messenger RNA transcripts. miRNAs play major roles in normal developmental processes, and their deregulation significantly contributes to various aspects of carcinogenesis. Nevertheless, in vivo delivery of small interfering RNA (siRNA) and miRNA remains a crucial challenge for their therapeutic success. siRNAs and miRNAs on their own are not taken-up by most mammalian cells in a way that preserves their activity. In order to circumvent these limitations, we developed a cationic carrier system, which can strongly improve its stability, intracellular trafficking and silencing efficacy. Polyglycerol (PG)-Amine, a water-soluble polyglycerol-based hyperbranched polymer accumulates in the tumor microenvironment due to the enhanced permeability and retention (EPR) effect, and therefore, represents an ideal nanocarrier for antitumor biological agents. Using our novel nanocarrier, we have studied the expression targets and functional effects of miR-34a in several human glioblastoma cell lines and human tissue samples. miR-34a levels inversely correlated to their target gene levels measured in the same cell lines or tissue. Transient transfection of PG-NH2-miR-34a polyplex into glioblastoma cells strongly inhibited cell proliferation, cell cycle progression, and cell migration. Consequently, we performed an in vivo experiment and achieved a significant tumor growth inhibition effect following treatment with PG-NH2-miR-34a polyplex in a human glioblastoma mouse model. We further characterized the synergistic effect of combining PG-NH2-miR-34a polyplex with chemotherapy and achieved promising results. Together, our findings show that PG-NH2 efficiently delivers anticancer miRNAs to glioblastoma cells and suppresses brain tumor growth. These results suggest that our polyplex could serve as a potential nanomedicine for glioblastoma. Citation Format: Paula Ofek, Marcelo Calderon, Fatemeh Sheikhi-Mehrabadi, Shiran Ferber, Rainer Haag, Ronit Satchi-Fainaro. Multi-modal nanomedicine for glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4391. doi:10.1158/1538-7445.AM2014-4391

Imaging of doxorubicin release from theranostic macromolecular prodrugs via fluorescence resonance energy transfer.

Herein we present a FRET-based theranostic macromolecular prodrug (TMP) composed of (a) dendritic polyglycerol (PG) as polymeric nanocarrier, (b) doxorubicin (Dox) linked via a pH-sensitive hydrazone to (c) a tri-functional linker, and (d) an indodicarbocyanine dye (IDCC) attached in close proximity to Dox. The drug fluorescence is quenched via intramolecular FRET until the pH-sensitive hydrazone bond between the TMP and Dox is cleaved at acidic pH. By measuring its fluorescence, we characterized the TMP cleavage kinetics at different pH values in vitro. The intracellular release of Dox from the carrier was monitored in real time in intact cancer cells, giving more insight into the mode of action of a polymer drug conjugate.

Platinum on Nanodiamond: A Promising Prodrug Conjugated with Stealth Polyglycerol, Targeting Peptide and Acid‐Responsive Antitumor Drug

In the field of nanomedicine, nanoparticles with various functions are required for in vivo applications such as biomedical imaging and drug delivery. Therefore, chemical functionalization of nanoparticles has been extensively investigated. Herein, nanodiamond (ND) coated with polyglycerol (PG) and its derivatives is reported to impart good solubility in a physiological environment, a stealth nature to avoid nonspecific uptake, a targeting property to be taken up by a specific cell, and an acid‐responsive drug release property to kill cancer cells. ND is first grafted with PG and the resulting ND‐PG has a high solubility in physiological media. Since a large number of hydroxyl groups in PG provide scaffolds for further surface functionalization, the targeting RGD peptide and Pt‐based drug are immobilized to give ND‐PG‐RGD, ND‐PG‐Pt and ND‐PG‐RGD‐Pt. The ND with intrinsic fluorescence is also functionalized by PG and RGD to confirm cellular uptake and intracellular localization fluorescently. The results of the cell experiments indicate that PG coating shielded fND from the uptake by HeLa and U87MG cells. In contrast, fND‐PG‐RGD is taken up by U87MG, not HeLa cells, exhibiting high targeting efficacy. When ND‐PG‐RGD‐Pt is applied, U87MG is selectively killed against HeLa. The multi‐functional ND is a promising prodrug in targeting chemotherapy.

Synthesis and Surface‐Active Behavior of New Fluorinated Hyperbranched Polymer

AbstractIn this article, a series of novel hyperbranched fluorinated polymer with polyglycerol (PG) as the hydrophilic core and poly(2,2,2‐trifluoroethyl methacrylate) (PTFEMA) as solvophobic arms were synthesized. When the atom transfer radical polymerization was carried out using N,N‐dimethylformamide (DMF) as the solvent, [M]/[I] ratio of 200, and [CuBr]/[NBr] ratio of 0.1 at 30 °C, controlled polymerization was achieved. The surface active properties of the polymer at the dimethyl sulfoxide (DMSO)/air and chloroform/water interface were studied by pendant drop measurements. The results showed that the copolymers could reduce surface tension (interfacial tension) in a manner analogous to the conventional surfactant in aqueous solutions. Thermodynamic analysis suggested that the solvophobic PTFEMA chains play an important role in determining the driving force of the aggregate formation in DMSO.

Polyglycerol-coated nanodiamond as a macrophage-evading platform for selective drug delivery in cancer cells

A successful targeted drug delivery device for cancer chemotherapy should ideally be able to avoid non-specific uptake by nonmalignant cells, particularly the scavenging monocyte-macrophage system as well as targeting efficacy to bring the drug preferentially into tumor cells. To this purpose, we developed a platform based on detonation nanodiamond (dND) with hyperbranched polyglycerol (PG) coating (dND-PG). dND-PG was first demonstrated to evade non-specific cell uptake, particularly by macrophages (U937). RGD targeting peptide was then conjugated to dND-PG through multistep organic transformations to yield dND-PG-RGD that still evaded macrophage uptake but was preferentially taken up by targeted A549 cancer cells (expressing RGD peptide receptors). dND-PG and dND-PG-RGD showed good aqueous solubility and cytocompatibitlity. Subsequently, the anticancer agent doxorubicin (DOX) was loaded through acid-labile hydrazone linkage to yield dND-PG-DOX and dND-PG-RGD-DOX. Their cellular uptake and cytotoxicity were compared against DOX in A549 cells and U937 macrophages. It was found that dND-PG-DOX uptake was substantially reduced, displaying little toxicity in either type of cells by virtue of PG coating, whereas dND-PG-RGD-DOX exerted selective toxicity to A549 cells over U937 macrophages that are otherwise highly sensitive to DOX. Finally, dND-PG was demonstrated to have little influence on U937 macrophage cell functions, except for a slight increase of TNF-α production in resting U937 macrophages. dND-PG is a promising drug carrier for realization of highly selective drug delivery in tumor cells through specific uptake mechanisms, with minimum uptake in and influence on macrophages.

Facile Williamson etherification of hyperbranched polyglycerol and subtle core-dependent supramolecular guest selection of the resulting molecular nanocapsule

O-alkylation of highly polar polyglycerol with alkyl bromides, promoted just by sodium hydroxide in dimethyl sulfoxide (DMSO), is reported. Zimmermann–Dathe type Williamson etherification, which can be carried out by a mild base in DMSO, is very useful in preparing ethers. However, it is always limited to alkyl chlorides or methyl halides due to the elimination reaction. In this contribution, this reaction is promoted to alkyl bromides and iodides just by decreasing the reaction temperature and then it is further applied in preparing a series of O-alkylated hyperbranched polyglycerol (PG). It is found per-alkylation of PG is possible regardless of its dense hydroxyl groups. In addition, the modified method shows selectivity over the halogen species. The resulting core–shell amphiphilic macromolecules (CAMs) can be used for dye encapsulation and they show core-dependent selection over the dye species. For example, the ether-based CAM 1b (PG–O–(C16)0.61, 61% of OH groups are O-alkylated by cetyls) is with limited difference from the ester-based CAM 2a (PG–COO–(C16)0.60), but they show very different guest selection. Controlled release is also available by core design of the CAMs.

Application of Polyglycerol Coating to Plasmid DNA Lipoplex for the Evasion of the Accelerated Blood Clearance Phenomenon in Nucleic Acid Delivery

Cationic liposomes (CLs) have shown promise as nonviral delivery systems. To achieve in vivo stability and long circulation, most liposomes are modified with hydrophilic polymer polyethylene glycol (PEG). However, we have reported that repeated administration of PEG-coated CLs containing plasmid DNA (pDNA; PEGylated lipoplexes) induces what is referred to as “the accelerated blood clearance (ABC) phenomenon” and, consequently, subsequently administered lipoplexes lose their prolonged circulation characteristics. Anti-PEG IgM produced in response to the first dose of PEG-coated pDNA–lipoplexes (PEG–DCL) has proven to be a major cause of the ABC phenomenon. In this study, to evade and/or attenuate this unexpected immune response, we modified the surface of a lipoplex with polyglycerol (PG)-derived lipid. The PG-coated pDNA–lipoplex (PG–DCL) attenuated the production of anti-polymer IgM, whereas PEG-coated pDNA–lipoplex (PEG–DCL) did not. In addition, a second dose of PG–DCL maintained the accumulation level in the tumor tissue of a tumor-bearing mouse model, comparable to that of the first dose, whereas the tumor accumulation level of a second dose of PEG–DCL was significantly compromised, compared with the first dose of PEG–DCL. Our results indicate that surface modification of lipoplex with PG represents a viable means for the attenuation, and/or evasion, of the ABC phenomenon that is encountered upon repeated administrations of nucleic acids containing PEG-coated nanocarriers.

Dendronized core-multishell nanocarriers for solubilization of guest molecules

AbstractWe have synthesized core-multishell (CMS) nanocarriers with different outer shells and the self-aggregation behavior and the transport capacity of these nanocarriers were studied with the hydrophobic guest molecules Nile red (NR) and methotrexate (MTX). The outer shell either consisted of methoxypoly(ethylene glycol) (mPEG) or polyglycerol (PG) dendrons of generation one or two. NR was solubilized by all CMS nanocarriers. The solubilization of MTX could only be achieved with mPEG-terminated CMS nanocarriers. Depending on the encapsulated guest, the CMS nanocarriers showed self-aggregation. The NR loaded CMS nanocarriers all formed bigger aggregates with a radius between 110 and 170 nm. In the case of the MTX loaded CMS nanocarriers, the MTX prevented the formation of CMS aggregates and therefore its efficient transport

Use of polyglycerol (PG), instead of polyethylene glycol (PEG), prevents induction of the accelerated blood clearance phenomenon against long-circulating liposomes upon repeated administration

The accelerated blood clearance (ABC) phenomenon accounts for the rapid systemic clearance of PEGylated nanocarriers upon repeated administrations. IgM production against the polyethylene glycol (PEG) coating in PEGylated liposomes is now known to be responsible for such unexpected pharmacokinetical alterations. The ABC phenomenon poses a remarkable clinical challenge by reducing the therapeutic efficacy of encapsulated drugs and causing harmful effects due to the altered tissue distribution pattern of the drugs. In this study, we investigated the in vivo performance of liposomes modified with polyglycerol (PG) upon repeated injection, and the in vivo therapeutic efficacy of such liposomes when they encapsulated a cytotoxic agent, doxorubicin (DXR). Repeated injection of PEG-coated liposomes in rats induced the ABC phenomenon, while repeated injection of PG-coated liposomes did not. In addition, DXR-containing PG-coated liposomes showed antitumor activity that was superior to that of free DXR and similar to that of DXR-containing PEG-coated liposomes upon repeated administration. These results indicate that polyglycerol (PG) might represent a promising alternative to PEG via enhancing the in vivo performance of liposomes by not eliciting the ABC phenomenon upon repeated administration.

Direct grafting of anti-fouling polyglycerol layers to steel and other technically relevant materials

Direct grafting of hyperbranched polyglycerol (PG) layers onto the oxide surfaces of steel, aluminum, and silicon has been achieved through surface-initiated polymerization of 2-hydroxymethyloxirane (glycidol). Optimization of the deposition conditions led to a protocol that employed N-methyl-2-pyrrolidone (NMP) as the solvent and temperatures of 100 and 140°C, depending on the substrate material. In all cases, a linear growth of the PG layers could be attained, which allows for control of film thickness by altering the reaction time. At layer thicknesses >5nm, the PG layers completely suppressed the adhesion of albumin, fibrinogen, and globulin. These layers were also at least 90% bio-repulsive for two bacteria strains, E. coli and Acinetobacter baylyi, with further improvement being observed when the PG film thickness was increased to 17nm (up to 99.9% bio-repulsivity on silicon).

ChemInform Abstract: Recent Developments in Acid‐ and Base‐Catalyzed Etherification of Glycerol to Polyglycerols

AbstractReview: 37 refs.

Polyglycerol‐Tagged Molecular Clips as Receptors in Protic Solvents

AbstractFour charge‐neutral molecular clips modified with polyglycerol (PG) dendrons of first and second generation and with hyperbranched polyglycerols (HPG) in the central unit as solubilizing units were synthesized. Their use as supramolecular hosts for the complexation of several guest molecules such as caffeine, N‐methylnicotinamide iodide, and Kosower salt was studied in methanol and water. Association constants and Gibbs enthalpies of association were determined by 1H NMR titration experiments. The obtained results were compared to the association behavior of molecular clips that carry anionic substituents. These results offer remarkable insights into the contribution of the substituents to host–guest binding and enable a strategy for improved substituent design.

Hyperbranched Polyglycerol‐Grafted Superparamagnetic Iron Oxide Nanoparticles: Synthesis, Characterization, Functionalization, Size Separation, Magnetic Properties, and Biological Applications

AbstractFor biomedical application of nanoparticles, the surface chemical functionality is very important to impart additional functions, such as solubility and stability in a physiological environment, and targeting specificity as an imaging probe and a drug carrier. Although polyethylene glycol (PEG) has been used extensively, here, it is proposed that hyperbranched polyglycerol (PG) is a good or even better alternative to PEG. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared using a polyol method are directly functionalized with PG through ring‐opening polymerization of glycidol. The resulting SPION‐PG is highly soluble in pure water (>40 mg mL−1) and in a phosphate buffer solution (>25 mg mL−1). Such high solubility enables separation of SPION‐PG according to size using size exclusion chromatography (SEC). The size‐separated SPION‐PG shows a gradual increase in transverse relaxivity (r2) with increasing particle size. For biological application, SPION‐PG is functionalized through multistep organic transformations (–OH → –OTs (tosylate) → –N3 → –RGD) including click chemistry as a key step to impart targeting specificity by immobilization of cyclic RGD peptide (Arg‐Gly‐Asp‐D‐Tyr‐Lys) on the surface. The targeting effect is demonstrated by the cell experiments; SPION‐PG‐RGD is taken up by the cells overexpressing αvβ3‐integrin such as U87MG and A549.

Abstract 5650: Targeting siRNA to tumors and their stroma as a dual anticancer and anti-angiogenic therapy

Abstract New targets for RNA interference (RNAi)-based cancer therapy are constantly emerging from the increasing knowledge on the molecular pathways involved in carcinogenesis. Nevertheless, in vivo delivery of small interfering RNA (siRNA) remains a crucial challenge for its therapeutic success. SiRNAs on their own are not taken-up by most mammalian cells in a way that preserves their activity. In order to circumvent these limitations, we developed a cationic carrier system, which can strongly improve its stability, intracellular trafficking and silencing efficacy. We have recently developed a polyglycerol (PG)-Amine, a water-soluble polyglycerol-based dendrimer that accumulates in the tumor environment due to the enhanced permeability and retention (EPR) effect, and therefore, represents an ideal delivery vehicle for antitumor biological agents. PG-Amine entrapment of siRNA neutralized its negative charge in a dose-dependent manner and significantly improved its cellular uptake. The luciferase gene, ectopically overexpressed in U87 human glioblastoma cell line was used as a model system and its silencing efficacy was extensively evaluated both in vitro and in vivo. Following encouraging results obtained from several cancer cell lines, the silencing efficiency of the nanocarrier luciferase-siRNA polyplexes was followed-up in vivo by non-invasive intravital bioluminescence imaging. A significant gene silencing effect was accomplished in vivo in both human glioblastoma and murine mammary adenocarcinoma mouse models following intravenous administration of our polyplexes. We further characterized the effect of silencing a few selected key proteins (e.g. Notch1) in vitro and achieved significant effects on the proliferation and migration of glioblastoma and neuroblastoma cell lines. In conclusion, we predict that specific delivery of siRNA to tumor epithelial and endothelial cells in vivo, and silencing of an important cell growth and angiogenesis regulator will warrant this approach as a successful anticancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5650. doi:1538-7445.AM2012-5650

Squaric Acid Mediated Synthesis and Biological Activity of a Library of Linear and Hyperbranched Poly(Glycerol)–Protein Conjugates

Polymer-protein conjugates generated from side chain functional synthetic polymers are attractive because they can be easily further modified with, for example, labeling groups or targeting ligands. The residue specific modification of proteins with side chain functional synthetic polymers using the traditional coupling strategies may be compromised due to the nonorthogonality of the side-chain and chain-end functional groups of the synthetic polymer, which may lead to side reactions. This study explores the feasibility of the squaric acid diethyl ester mediated coupling as an amine selective, hydroxyl tolerant, and hydrolysis insensitive route for the preparation of side-chain functional, hydroxyl-containing, polymer-protein conjugates. The hydroxyl side chain functional polymers selected for this study are a library of amine end-functional, linear, midfunctional, hyperbranched, and linear-block-hyperbranched polyglycerol (PG) copolymers. These synthetic polymers have been used to prepare a diverse library of BSA and lysozyme polymer conjugates. In addition to exploring the scope and limitations of the squaric acid diethylester-mediated coupling strategy, the use of the library of polyglycerol copolymers also allows to systematically study the influence of molecular weight and architecture of the synthetic polymer on the biological activity of the protein. Comparison of the activity of PG-lysozyme conjugates generated from relatively low molecular weight PG copolymers did not reveal any obvious structure-activity relationships. Evaluation of the activity of conjugates composed of PG copolymers with molecular weights of 10000 or 20000 g/mol, however, indicated significantly higher activities of conjugates prepared from midfunctional synthetic polymers as compared to linear polymers of similar molecular weight.

Dendritic polyglycerolamine as a functional antifouling coating of gold surfaces

Dendritic polyglycerol (PG) functionalized surfaces represent a good alternative for preparation of protein resistant materials, whose versatility can be enhanced by conferring them the ability to bind particular biomolecules of interest to the surface. In this work, PG derivatives bearing disulfide and different loadings of amino moieties (0–14%) were synthesized and attached to gold surfaces. The modified surfaces were characterized by means of infrared reflection adsorption spectroscopy (FT-IRRAS), X-ray photoelectron spectroscopy (XPS), and contact angle measurements. The protein resistance properties of the PG-modified surfaces were evaluated by surface plasmon resonance (SPR) spectroscopy using fibrinogen, albumin, pepsin, and lysozyme as model proteins. The availability and accessibility of the amino groups to bind biomolecules were assessed by fluorescence measurements. This study demonstrates that PG-coated surfaces with amino contents up to 9% still show very good protein resistant properties. At the same time, the amino moieties on the surface are available and reactive for selective ligand attachment. By fluorescence labeled DNA hybridization, the high selectivity of these functional surfaces could be demonstrated.

Mesogen-Initiated Linear Polyglycerol Isomers: The Ordering Effect of a Single Cholesterol Unit on “Sticky” Isotropic Chains

Synthesis, thermal properties, and the liquid crystalline (LC) order of polymers consisting of a single mesogenic cholesterol unit and flexible, linear polyglycerol (PG) or poly(glyceryl glycerol) (PGG) chains have been investigated. Incorporation of the single mesogen has been achieved by using cholesterol directly as an initiator for the oxyanionic ring-opening polymerization (ROP) of ethoxyethyl glycidyl ether (EEGE) or isopropylidene glyceryl glycidyl ether (IGG). The controlled polymerization allowed the synthesis of a series of peculiar rod–coil type polyethers with molecular weights of 600–2300 g/mol, representing a degree of polymerization (DPn) of 4–30 for both PG and PGG with the polydispersity Mw/Mn in the range of 1.07–1.25. The resulting linear PGs exhibit extremely stable thermotropic LC order in a broad temperature range up to 260 °C, forming mainly layered smectic A (SmA) phases with varying layer thicknesses, depending on the degree of polymerization of the respective polymer structure. LC phases were observed up to a chain length of 26 glycerol units, while PGGs showed no LC order. This is explained both by the steric hindrance of the branched monomer units and the higher hydrophilicity of the polymer backbone. Permethylation of the cholesterol-PG samples resulted in strongly reduced LC order or in the entire loss of the self-assembly in LC phases, which is a consequence of the disappearance of hydrogen-bonding between the functional coil segments. Detailed characterization of the phase behavior of the polymers has been achieved by differential scanning calorimetry (DSC), polarized optical microscopy (POM), and small-angle X-ray scattering (SAXS), confirming the smectic layer structure of the materials.