The increasing need for drug delivery systems that improve specificity and activity and at the same time reduce toxicity to ensure maximum treatment safety has led to the development of a great variety of drug vectors. Carriers based on soft matter have particularly interesting characteristics. Herein we present the current standing of the research in this area, and focus on two main families, namely matrix systems and vesicles. We outline the structure, properties, and potential applications of these vectors, and discuss their main advantages and drawbacks in their synthesis.
Structures formed by self-assembly of α- and β-1-n-dodecyl d-maltosides in water depend on the configuration at the anomeric center. The α-anomer forms quasi-spherical aggregates, while the β-maltoside forms larger oblate ellipsoidal micelles. This difference in behavior suggests that the configuration of the head group influences the orientation of the polar residue and hence the packing of monomers during self-assembly.
Galactosylceramide (GalCer) is an alternative receptor allowing human immunodeficiency virus (HIV)-1 entry into CD4-negative cells of neural and colonic origin.Several lines of evidence suggest that this glycosphingolipid recognizes the V3 region of HIV-1 surface envelope glycoprotein gp120. Since the V3 loop plays a key role in the fusion process driven by HIV-1, we decided to synthesize soluble analogs of GalCer with the aim to develop a new class of anti-HIV-1 agents that could neutralize HIV-1 infection through masking of the V3 loop. We describe a short route, in three steps, for the synthesis of soluble analogs of GalCer, using unprotected lactose as the starting sugar. The analogs were prescreened in an assay based on the interaction between a V3 loopderived synthetic peptide and [ 3 H]suramin, a polysulfonyl compound displaying high affinity for the V3 loop. One of the soluble analogs, i.e. CA52(n15), strongly inhibited the binding of [ 3 H]suramin to the V3 peptide, with an IC 50 of 1.2 M. This molecule was also able to inhibit [ 3 H]suramin binding to recombinant gp120 with similar activity. Using a competition enzyme-linked immunosorbent assay with highly specific anti-gp120 monoclonal antibodies, the region recognized by CA52(n15) could be mapped to amino acids 318 -323, which corresponds to the highly conserved consensus motif GPGRAF. Interestingly, the region recognized by suramin, i.e. IQRGP-R-F, was partially overlapping this motif. CA52(n15) was able to inhibit HIV-1-induced cell fusion as well as HIV-1 entry into both CD4 ؉ and CD4 ؊ / GalCer ؉ cells. A structure-activity relationship study showed that: (i) the antiviral activity of soluble analogs of GalCer correlates with V3 loop binding, and (ii) the hydrophobic moiety of the molecule plays an important role in this activity. Taken together, these data show that synthetic analogs of GalCer can inhibit HIV-1 entry into both CD4 ؊ and CD4 ؉ cells through masking of the V3 loop.
New double-chain and gemini catanionic analogues of the glycolipid galβ1ceridentified as a cell receptor of the HIV-1 viruswere easily prepared in two steps from unprotected lactose. Due to their sugar moiety, these new catanionic surfactants were able to be cationized by sodium ions and therefore to be characterized in their monomeric forms by electrospray mass spectrometry. To our knowledge, this is the first time that catanionic surfactants have been directly observed, proving undoubtedly their existence as monomeric species. These new catanionic glycolipids showed interesting anti-HIV-1 activities, acting as monomeric analogues of galβ1cer. Finally, these new catanionic glycolipids were characterized by their surface active properties, by lamellar mesophases, and by their aptitude to spontaneously form vesicles.
In this work we investigate lyotropic phases in different sugar-based surfactantlwater systems. Studies are carried out with the (N-alky1amino)-1-deoxylactitols (CS, C10, CIZ) and P-dodecyl maltoside. Liquid crystal phases are detected and lattice parameters determined by X-ray diffraction. The phases observed are the normal phases found in binary ionic or nonionic surfactantlwater systems. Schematic diagrams show the sequences of the lyotropic phases formed by these disaccharide surfactants. The difference in behavior is accounted for by the difference in chain length, hydrophilic ability, and steric hindrance of the polar head. IntroductionSurfactants derived from sugars form a large class of amphiphiles, which are currently receiving attention in view of their excellent biocompatibility and biodegradabi1ity.l Among the numerous applications of these compounds mention can be made of extraction and crystallization of membrane proteins2 and emulsification of substrates for enzymatic reaction^.^The first studies on the associative properties of these compounds were devoted to the solid-solid phase transitions and the liquid crystal properties of alkyl derivatives of carbohydrates in which the alkyl chain contained generally a t least eight carbon a t o m~.~-l~ Micellization of compounds of this family has been the subject of a few studies.13-15 More recently the surface properties of monolayers and the forces between bilayers of gangliosides
Successful one-pot preparation of a hyperbranched polymer chemically analogous to PAMAM dendrimers was achieved and its use for metal nanocluster stabilization is reported. When compared to PAMAM, such experiments demonstrate clearly the effect of the macromolecular architecture on the formation of the inorganic nanoparticles.Small metal particles have quite unique optical, electronic, and catalytic properties that result from size, shape, and size distribution effects.The preparation of such metal colloids requires the use of stabilizers which prevent the thermodynamically favored aggregation of the nanoparticles in solution. Various well-known compounds (e.g., water-soluble polymers, surfactants, etc.) have been employed as stabilizers. 1 Dendrimers have also been used as nanoreactors in which metal cations are localized before reduction leading to stabilized metal nanoparticles of a few nanometers, 2 this small size being presumably related to the unique structure of the dendrimers. However, the costly synthesis of dendrimers is prohibitive for many applications. In contrast to those perfectly branched monodisperse dendrimers, randomly branched (i.e., hyperbranched) polymers can be easily accessible 3 and they can effectively stabilize metal nanoparticles in organic solvents. 4 To our knowledge, no attempt has been made, up to now, to compare nanoparticles obtained from reduction of metal salts complexed with dendrimer and hyperbranched polymer.In this work, we present the synthesis and characterization of a hyperbranched polymer that is chemically analogous and close in molecular weight to the 4th generation of PAMAM dendrimers (noted PAMAM4). Because of this similarity in the molecular weights, this hyperbranched polymer was noted HYPAM4. Characterization of gold nanoparticles prepared using these polymers is also described.Polymer Synthesis 5 and Characterization. The synthesis of hyperbranched polyamidoamines with a structure similar to the one of PAMAM dendrimers was based on a method described by Dvornic, 6 where a hexaester was reacted with a triamine (Figure 1). This method has the strong advantage of leading to hyperbranched architectures in a single step and can be carried out in large quantities. By adjusting the mole ratio between the hexaester and the triamine for the polymer synthesis, control of the final molar mass of the hyperbranched polymer can be experimentally achieved. We have focused our work on the samples obtained when a triamine/hexaester mixture of 10:1 ratio was used for the synthesis. Clearly, the characterization of this polymer demonstrates that HYPAM4 is quite comparable to the highly used PAMAM dendrimer of the 4th generation. Molar masses are very close for both compounds, as are the numbers of primary and tertiary amines (see Table 1) (by construction, HYPAM4 has, however, less amide functions when compared to PAMAM4). Indeed, to check the chemistry of the hyperbranched polymer, the quantification of amine groups was carried out by several methods. The most reliable results ...
Two series of water-soluble dendritic catanionic assemblies, acting as multisite analogues of galactosylceramide (Galbeta1cer), have been prepared with the goal of blocking HIV infection prior to the entry of the virus into human cells. Trifunctional and hexafunctional cinnamic acid-terminated dendrimers have been synthesized from phosphorus-containing dendrimers bearing aldehyde end groups. A classical acid-base reaction performed in water between acid-terminated dendrimers and stoichiometric amounts of N-hexadecylamino-1-deoxylactitol provided the expected catanionic assemblies. Antiviral assays on these supramolecular entities confirmed the crucial roles both of multivalency effects and of lipophilicity on the biological activity of Galbeta1cer analogues. Moreover, correlation between in vitro tests and molecular modeling highlights the specific influence of the assembly shape on the anti-HIV efficiency, with the tri- and hexafunctional cored dendrimers, both decorated with 12 sugar moieties, exhibiting IC50 values of 1.1 and 0.12 microM, respectively.
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