Biomedical subjects

Chandrasekaran Ramaswamy

Publications and source records attributed to Chandrasekaran Ramaswamy.

4 recordsLinked to original sources

PubMed2006

Protein transduction by lipidic peptide dendrimers.

We investigated the potential of a new family of lipidic peptide dendrimers in protein transduction into cultured cells. Dendrimer-protein interaction was determined by gel retardation assays using purified recombinant protein. To assess intracellular protein delivery, two marker proteins were used: recombinant firefly luciferase and a Cy3-labeled monoclonal antibody to the c-myc proto-oncogene. Protein delivery was determined by luciferase assays and fluorescence microscopy, respectively. While there was minimal delivery of luciferase or antibody in the absence of the dendrimers, the latter increased protein delivery substantially. Luciferase delivery was concentration and cell type-dependent; the efficiency of delivery also varied with the number of terminal amino groups on the dendrimers. In previous reports, we showed that these dendrimers could be used for gene and drug delivery; the data we report herein suggest that they may also be capable of intracellular protein delivery. This finding has important implications for the use of these dendrimers in protein therapeutics and vaccinology.

Antibodies, Monoclonal↗

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

Investigation of the association and flexibility of cationic lipidic peptide dendrons by NMR spectroscopy.

The cationic peptide dendrons synthesized and studied are lower generation polylysine-based partial dendrimers with or without lipid chains in the core. The dendrons with lipidic chains can be utilized as protein and liposomal mimics because of their unique structural properties. The full assignments of three different dendrons (L)7(NH2)8, (C14)1(L)7(NH2)8 and (C14)3(L)7(NH2)8 were obtained in D2O and H2O/D2O using a 500 MHz NMR spectrometer. The hydrophobic lipidic core of branched polylysine dendrons was found to induce aggregation upon increasing concentration. Because non-lipidic dendrons do not self-assemble, the behaviour and internal structural features of two different dendrons with one and three C14 hydrocarbon chains were explored. The critical association concentration clearly depends on the number of core hydrophobic residues and the association starts at 0.025 mM for (C14)1(L)7(NH2)8 and 0.05 mM for (C14)3(L(7(NH2)8. Chemical shift analysis also revealed that the hydrophobic chains of the dendrons associate in the core, whereas the polar head groups (NH2) are mainly located at the surfaces of the aggregates. The T1 relaxation time measurements showed that the mobility of the hydrocarbon chain is greater with the monomeric form of dendron (C14)1(L)7(NH2)8) than that of monomer (C14)3(L)7(NH2)8. The inter-chain hydrophobic interactions restrict the flexibility of the dendron with three hydrocarbon chains. As expected, the flexibility of the monomeric form is higher than that of the aggregated state for both of the dendrons.

Lipoproteins↗

PubMed2003

Dendriplexes and their characterisation.

The interaction of DNA with partial dendrimers (dendritic polylysine containing seven lysines and eight terminal amino groups with or without a lipidic core) was studied. Compact complexes were formed which we term "dendriplexes". Agarose gel electrophoresis and exclusion of ethidium bromide confirmed the interaction. All the dendrons formed compact complexes above a 2:1 (+/-) charge ratio in water and HBSS. Photon correlation spectroscopy, electron microscopy and zeta potential measurements were used to determine, respectively, the particle size, shape and surface charge of the dendriplexes. The z-average diameter of the dendriplexes were found to be 60-70 nm irrespective of the dendron used and the zeta potential varied from 10 to 35 mV at a 3:1 (+/-) charge ratio depending on the dendron. The protection of the DNA component of these dendriplexes from nuclease degradation was confirmed by DNase protection assays.

Chemical Phenomena↗