Biomedical subjects

Khuloud T Al-Jamal

Publications and source records attributed to Khuloud T Al-Jamal.

4 recordsLinked to original sources

PubMed2006

An intrinsically fluorescent dendrimer as a nanoprobe of cell transport.

Dendrimers, spherical or quasi-spherical synthetic polymers in the nano-size range, have found useful applications as prospective carriers in drug and gene delivery. The investigation of dendrimer uptake by cells has been previously achieved by the incorporation of a fluorescent dye to the dendrimer either by chemical conjugation or by physical interaction. Here we describe the synthesis of two intrinsically fluorescent lysine based cationic dendrimers which lack a fluorophore, but which has sufficient fluorescence intensity to be detected at low concentrations. The nomenclature used to describe our compounds results in, for example the 6th generation dendrimer being notated as Gly-Lys(63) (NH2)(64); Gly denotes that the compound has a glycine in the core coupled to 63 lysine branching units (Lys(63)) and that the surface has 64 free amino groups (NH2)(64). The use of these dendrimers in probing transport avoids the need for fluorescent tagging with its attendant problems. The uptake of Gly-Lys(63) (NH2)(64) into Caco-2 cells was followed using confocal microscopy. Being cationic, it first adsorbs to the cell surface, enters the cytoplasm and reaches the nucleus within 35-45 min. Estimates of the diffusion coefficient of the dendrimer within the cell cytoplasm leads to a value of 6.27 ( +/- 0.49) x 10(-11) cm(2) s(-1), which is up to 1000 times lower than the diffusion coefficient of the dendrimer in water. Intrinsically fluorescent dendrimers of different size and charge are useful probes of transport in cells.

Biological Transport↗

PubMed2005

Supramolecular structures from dendrons and dendrimers.

This paper reviews aspects of the association of dendrons and dendrimers into a variety of supramolecular structures. There is such a wide range of primary dendron and dendrimer chemistries that it is still difficult to predict behaviour in aqueous media, and there are few studies in non-aqueous media. The aggregation of the primary units into larger and more complex forms leads to a wider range of potential carrier systems for drugs, genes and vaccines. This review deals principally with the association structures which can be formed. These include liquid crystalline structures and dendron block copolymer aggregates, surface monolayer formation, dendrimer derived nanoparticles, micellar structures and dendrisome (vesicle) formation. Of particular interest are DNA-dendrimer complexes and dendrimer-polyanion interactions. The in vivo behaviour of dendrons and dendrimers is of course crucial and is addressed. Dendrimer vesicle solubilisation by surfactants and emulsion stabilisation by dendrimers completes the survey of secondary structures. The challenge is to understand better the processes involved and to concentrate further on the design of the synthesis of dendrons and dendrimers which will associate into specific complex structures to increase the scope of dendrimer science.

DNA↗

PubMed2005

Dendrisomes: vesicular structures derived from a cationic lipidic dendron.

The behavior of a novel synthetic lipidic cationic lysine-based dendron (partial dendrimer) in aqueous media and its ability, with and without cholesterol, to self-assemble into higher order structures was studied to gain an understanding of these structures as potential drug carriers. The dendron was prepared by solid-phase peptide synthesis. A reverse-phase evaporation (REV) technique was used to prepare cationic vesicular aggregates of the dendron with different molar ratios of cholesterol. The size and zeta potential of these supramolecular aggregates or "dendrisomes" was determined by photon correlation spectroscopy (PCS). Dendrisome morphology and thermotropic properties were studied by transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). Radiolabeled penicillin G was used as a model of a negatively charged water-soluble compound to investigate the encapsulation efficiency of the dendrisomes. In vitro release of the drug was determined using as a comparator a REV liposome formulation. Dendrisomes of all compositions have higher encapsulation efficiencies and slower release rates compared to the comparator. Cholesterol was found both to increase the size of the aggregates from around 310 to 560 nm and to increase shape irregularities, but did not change the positive zeta potential, in the order of +50 mV, of the dendrisomes. Cholesterol decreases penicillin G entrapment efficiency but increases solute leakage at 25 degrees C.

Chemical Phenomena↗

PubMed2003

Dendrisomes: cationic lipidic dendron vesicular assemblies.

A new lipidic cationic polylysine dendron was prepared by solid-phase peptide synthesis. Its behaviour in aqueous media and its ability, with and without cholesterol, to form higher order structures, "dendrisomes", was studied to further our understanding of how dendrons interact with drug molecules and may be utilised as drug carriers. Dynamics simulations of the dendron show their flexibility. Incorporation of cholesterol increases the hydrodynamic diameter of the aggregates from 311 to 556 nm but does not affect their positive zeta potential (of the order of +50 mV). The dendrisomes encapsulated penicillin G (6.15% w/w) compared to only 1.4% w/w entrapment in REV liposomes of 1:1 distearoyl phosphatidylcholine:cholesterol. Cholesterol, however, decreases the entrapment efficiency. Electrostatic forces and H-bonding between the negatively charged drug and dendron amino groups are likely to be key in determining these interactions.

Chemical Phenomena↗