Constantinos M. Paleos

Supramolecular hydrogen-bonded liquid crystals

The role of hydrogen-bonding interactions in the formation and/or stabilization of liquid crystalline phases has been recognized in recent years and significant work has been conducted. Following the first and well-established examples of liquid crystal formation through the dimerization of aromatic carboxylic acids, several classes of compounds have been prepared by the interaction of complementary molecules, the liquid crystalline behaviour of which is crucially dependent on the structure of the resulting supramolecular systems. In this review the main classes of liquid crystals prepared through hydrogen-bonding interactions are presented, with the aim of establishing, in the first place, the diversity of organic compounds that can be used as building elements in the process of liquid crystal formation. Rigid-rod anisotropic or amphiphilic-type molecules, appropriately functionalized with recognizable moieties, interact in the melt or in solution and lead to the formation of supramolecular complexes that may exhibit thermotropic liquid crystalline character. Depending on the nature, number and position of the groups able to form hydrogen bonds, a diversity of supramolecular structures, both dimeric and polymeric, have been obtained, affording in turn various liquid crystalline phases. The structure and stability of these hydrogen-bonded supramolecular complexes and their relation to the observed liquid crystalline phases are the main topics of this review.

Poly(propyleneimine) Dendrimers as pH-Sensitive Controlled-Release Systems

Molecular composites were prepared by solubilizing pyrene in di- aminobutane poly(propyleneimine) den- drimers having 32 or 64 primary amine end groups (DAB-32 or DAB-64). The dendrimer - pyrene binding constants were determined as Kpy/DAB-32a 16 725 200m ˇ1 and Kpy/DAB-64a 33 858 663m ˇ1 by fluorescence spec- troscopy. Fluorescence studies were also employed to probe the release of pyrene from the interior of dendrimers as a function of pH. When the pH value of the system was decreased from pH 11 by addition of HCl, the fluorescence inten- sity of the system was found to increase by approximately tenfold at pH 2 - 4. In addition, at pH 2, the ratio of the first to the third vibrational peak of pyrene (I1/I3) increased from 0.9, the value typical for pyrene solvated in dendrimer solution, to 1.60, the value characteristic of pyrene in water. Pyrene release from the interior of dendrimers was con- firmed by fluorescence quenching when sodium iodide was added, since NaI does not affect the emission of dendrim- er-solubilized pyrene. Finally, fluores- cence quenching was used to locate the solubilization sites of pyrene within the dendrimer microcavities. These sites are close to the core of the dendrimer, near the tertiary amino groups which are also responsible for quenching the fluores- cence of the dendrimer-bound pyrene.

Drug delivery using multifunctional dendrimers and hyperbranched polymers

Importance of the field: The review presents the design strategy and synthesis of multifunctional dendrimers and hyperbranched polymers with the objective to develop effective drug delivery systems. Areas covered in this review: Well-characterized, commercially available dendritic polymers were subjected to functionalization for preparing drug delivery systems of low toxicity, high loading capacity, ability to target specific cells and transport through their membranes. This has been achieved by surface targeting ligands, which render the carriers specific to certain cells and polyethylene glycol groups, securing water solubility, stability and prolonged circulation. Moreover, transport agents facilitate transport through cell membranes while fluorescent probes detect their intracellular localization. A common feature of surface groups is multivalency, which considerably enhances their binding strength with complementary cell receptors. To these properties, one should also add the property of attaining high loading of active ingredients coupled with controlled and/or triggered release. What the reader will gain: Readers will be exposed to the strategy of synthesizing multifunctional polymers, aimed at the development of effective drug delivery systems. Take home message: Multifunctional systems upgrade the therapeutic potential of drugs and, in certain cases, may even lead to the application of new bioactive compounds that would otherwise not be feasible.

Liquid crystalline behaviour of hydrogen bonded complexes of a non-mesogenic anil with p-n-alkoxybenzoic acids

Phase diagrams of binary mixtures of the non-mesogenic N -(p -methoxy- o -hydroxybenzylidbe ene)- p -aminopyridine with a series of p - n -alkoxybenzoic acids ranging from methoxy to hexadecyloxy were established using differential scanning calorimetry and polarising optical microscopy. The key results obtained are: (1) the formation of 1 1 hydrogen bonded complexes between the pyridine derivative and the alkoxybenzoic acids, (2) the stability of the alkoxybenzoic acid mesophases over a wide range of compositions (up to slightly over 50 mol% of the pyridine derivative), (3) the absence of additional mesophases corresponding specifically to the 1 1 complexes, and (4) the complete miscibility of the acids with the complexes in the mesomorphic state. With alkoxy chains from methoxy to heptyloxy, mixtures produce only nematic phases; they produce both nematic and smectic phases with chains from octyloxy to dodecyloxy, and only smectic phases with chains from tetradecyloxy to hexadecyloxy. The formation of hyd...

Guanidinium group : A versatile moiety inducing transport and multicompartmentalization in complementary membranes

Guanidinium groups present in peptides and dendritic polymers induce their efficient transport through liposomal and cell membranes. Transmembrane crossing of these polymers is affected by their structural features and is critically dependent on the number of guanidinium groups present. Furthermore, the interaction of the guanidinium groups with phosphate groups, both located on liposomal surfaces, triggers a series of processes involving a reorganization of the self-assembled lipids and inducing the formation of multicompartment systems. These observations consistent throughout a diversity of interacting complementary liposomes, support a hypothesis that molecular recognition of liposomes induces the formation of multicompartment structures.

Chain extension of poly(ethylene terephthalate) by reactive blending using diepoxides

Molecular weight increase via chain extension reactions of poly(ethylene terephthalate) with commercially available diepoxides was studied in a custom-made laboratory scale reactor and a Brabender rheomixer under reactive blending conditions. The products were characterized by carboxylic end group analysis, intrinsic viscosity, and differential scanning calorimetry. PET was effectively modified in the laboratory-scale reactor using cyclic diepoxides because the resulting polymers show intrinsic viscosities that are comparable to virgin PET (0.68–0.75 dL/g vs. 0.74 dL/g) and much higher than processed PET (0.55), while carboxyl contents were reduced to a third of that of the virgin PET. Diglycidyl ethers produced polymers displaying decreased viscosity values, increased carboxyl content, and lower melting points. Low concentrations of extender and short reaction times generally favored chain extension. In addition, purging with nitrogen resulted in chain extended polymers having the highest values of intrinsic viscosity ([η] = 0.79, 0.82). Similar trends were observed with modified products in the rheomixer having somewhat smaller viscosity values, larger carboxyl contents, and increased melting points.

A Novel Micellar PEGylated Hyperbranched Polyester as a Prospective Drug Delivery System for Paclitaxel

A hyperbranched aliphatic polyester has been functionalized with PEG chains to afford a novel water-soluble BH40-PEG polymer which exhibits unimolecular micellar properties, and is therefore appropriate for application as a drug-delivery system. The solubility of the anticancer drug paclitaxel was enhanced by a factor of 35, 110, 230, and 355 in aqueous solutions of BH40-PEG of 10, 30, 60, and 90 mg x mL(-1), respectively. More than 50% of the drug is released at a steady rate and release is almost complete within 10 h. The toxicity of BH40-PEG was assessed in vitro with A549 human lung carcinoma cells and found to be nontoxic for 3 h incubation up to a 1.75 mg x mL(-1) concentration while LD50 was 3.5 mg x mL(-1). Finally, it was efficiently internalized in cells, primarily in the absence of foetal bovine serum, while confocal microscopy revealed the preferential localization of the compound in cell nuclei. [Figure: see text].

Gene delivery using functional dendritic polymers.

Objective: This review describes a strategy for the development of multifunctional dendritic polymers for application as gene delivery systems. These polymers can address the low transfection efficiency usually encountered by synthetic non-viral vectors. Methods: Employing appropriate, well-characterized and mainly commercially available dendritic polymers, the emphasis is placed primarily on step-wise molecular engineering of their surface for providing gene carriers of low toxicity, specificity to certain cells and transport ability through their membranes, with the ultimate objective of enhanced transfection efficiency. Cationic dendritic polymers interact with appropriate genetic material, affording complexes that are employed for cell transfection. Conclusion: Multifunctionalization of dendritic polymers provides gene vectors of low toxicity, significant transfection efficiency, specificity to certain biological cells and transport ability through their membranes.

A novel dendrimeric "glue" for adhesion of phosphatidyl choline-based liposomes

The interaction of phosphatidyl choline-cholesterol liposomes incorporating dihexadecyl phosphate as recognizable lipid with complementary guanidinylated diaminobutane poly(propylene imine) dendrimers of the fourth and fifth generation afforded liposome-dendrimer aggregates which were redispersed by the addition of an excess of a phosphate buffer. The higher generation dendrimeric derivative proved more effective when interacted with liposomes. This behavior was attributed to multivalent effects, which, as generally established, enhance the reactivity of multifunctional particles. Turbidimetry, atomic force microscopy (AFM) and optical microscopy were used for investigating the interaction of the complementary particles while the redispersion of the aggregates was studied by transmission electron microscopy (TEM). Liposomal membrane stability in the collapse and redispersion processes was assessed by the calcein fluorescence method, TEM, and AFM.

Molecular recognition of complementary liposomes in modeling cell-cell recognition.

Liposomes due to their structural features are considered as the closest analogues of biological cells. They can therefore be used as models for simulating cell ± cell interactions or interactions of cells with molecules of the extracellular environment. It is well established that some cell interactions are transient such as those between cells of the immune system and the interactions that direct white blood cells to sites of tissue inflammation. In other cases, stable cell ± cell junctions play the key role in the organization of cells in tissues. 2] It will therefore be challenging to elaborate, through molecular engineering processes, the shape, stability, and recognizable properties of the external surface of liposomes to render these particles susceptible to interaction with simple molecules or other liposomes. In this manner their behavior may mimic rather closely the processes occurring at the external surface of cells. Analogous phenomena may also be encountered in the interaction of living cells with liposomes when the latter are employed as drug delivery systems. 4] In connection with the recognition effectiveness of the interacting groups, as determined by their specific molecular structure, molecular recognition is enhanced relative to isotropic media since the interacting groups are located at the organized liposomal interface. In fact, the binding constants between complementary moieties differ by some orders of magnitude for various types of molecular organized aggregates. Cell ± cell adhesion realized by the interaction of the glycocalyx carbohydrate coat with proteins such as selectins or integrins was simulated by designing mixed liposomes. Such experiments were performed 9] and reviewed 11] years ago involving interactions followed by agglutination of polymerized liposomes, prepared from amphiphilic carbohydrates, with lectins, specifically concanavalin A. On the other hand, quite recently an artificial carbohydrate-binding receptor based on phospholipids bearing a boronic acid moiety has been employed since it has been established that boronic acid derivatives act as synthetic saccharide-binding receptors. 14] Carbohydrate ± protein recognition has thoroughly been investigated justifying a separate review by itself. In this Minireview we discuss some examples of molecular engineering the interacting surface of liposomes through the incorporation, among others, of recognizable moieties. The biomaterials obtained, characterized as tissue-like composites, were investigated primarily by microscopic and spectroscopic studies. Interacting liposomes were prepared following the strategy of incorporating recognizable moieties at the interface of liposomes and allowing the latter to interact either with simple molecules in the aqueous environment, or with other complementary liposomes. However, since liposomal adhesion and fusion has also been achieved electrostatically or, in some cases, by combined electrostatic forces and hydrogen bonding, some typical examples will be briefly discussed before proceeding to liposome aggregation that is mediated exclusively by hydrogen bonding based on molecular complementarity. Finally, proceeding one step further towards the biological reality, liposome ± cell and cell ± cell interactions will be discussed, employing recognizable moieties analogous to those used in the liposomal systems.