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1.
Int J Cardiol ; 220: 149-54, 2016 Oct 01.
Article in English | MEDLINE | ID: mdl-27379917

ABSTRACT

BACKGROUND: A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS: We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. RESULTS: Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. CONCLUSIONS: Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).


Subject(s)
Alginates , Angiotensin I , Myocardial Infarction , Peptide Fragments , Ventricular Function, Left/physiology , Ventricular Remodeling/drug effects , Alginates/chemistry , Alginates/pharmacology , Angiotensin I/chemistry , Angiotensin I/pharmacology , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Disease Models, Animal , Echocardiography/methods , Gelatin/pharmacology , Glucuronic Acid/chemistry , Glucuronic Acid/pharmacology , Hexuronic Acids/chemistry , Hexuronic Acids/pharmacology , Hydrogels/pharmacology , Injections, Intralesional/methods , Myocardial Infarction/physiopathology , Myocardial Infarction/therapy , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Rats , Rats, Sprague-Dawley , Treatment Outcome
2.
Med Hypotheses ; 79(5): 673-7, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22939314

ABSTRACT

Despite remarkable effectiveness of reperfusion and drug therapies to reduce morbidity and mortality following myocardial infarction (MI), many patients have debilitating symptoms and impaired left ventricular (LV) function highlighting the need for improved post-MI therapies. A promising concept currently under investigation is intramyocardial injection of high-water content, polymeric biomaterial gels (e.g., hydrogels) to modulate myocardial scar formation and LV adverse remodeling. We propose a degradable, bioactive hydrogel that forms a unique microstructure of continuous, parallel capillary-like channels (Capgel). We hypothesize that the innovative architecture and composition of Capgel can serve as a platform for endogenous cell recruitment and drug/cell delivery, therefore facilitating myocardial repair after MI.


Subject(s)
Alginates/chemistry , Myocardial Infarction/therapy , Stem Cell Factor/administration & dosage , Stem Cell Transplantation , Humans , Hydrogels , Microscopy, Electron, Scanning
3.
Nanotechnology ; 23(41): 415101, 2012 Oct 19.
Article in English | MEDLINE | ID: mdl-23010805

ABSTRACT

We describe a novel multicomponent graphene nanostructured system that is biocompatible, and has strong NIR optical absorbance and superparamagnetic properties. The fabrication of the multicomponent nanostructure system involves the covalent attachment of 3 components; Fe(3)O(4)(Fe) nanoparticles, PAMAM-G4-NH(2) (G4) dendrimer and Cy5 (Cy) on a graphene oxide (GO) surface to synthesize a biologically relevant multifunctional system. The resultant GO-G4-Fe-Cy nanosystem exhibits high dispersion in an aqueous medium, and is magnetically responsive and fluorescent. In vitro experiments provide a clear indication of successful uptake of the GO-G4-Fe-Cy nanosystem by MCF-7 breast cancer cells, and it is seen to behave as a bright and stable fluorescent marker. The study also reveals varied cellular distribution kinetics profile for the GO nanostructured system compared to free Cy. Furthermore, the newly developed GO nanostructured system is observed to be non-toxic to MDA-MB-231 cell growth, in striking contrast to free G4 dendrimer and GO-G4 conjugate. The GO-G4-Fe-Cy nanostructured system characterized by multifunctionality suggests the merits of graphene for cellular bioimaging and the delivery of bioactives.


Subject(s)
Breast Neoplasms/diagnosis , Carbocyanines , Dendrimers , Fluorescent Dyes , Graphite , Magnetite Nanoparticles , Nylons , Carbocyanines/chemistry , Carbocyanines/pharmacokinetics , Cell Line, Tumor , Cell Survival , Dendrimers/chemistry , Dendrimers/pharmacokinetics , Female , Fluorescent Dyes/chemistry , Fluorescent Dyes/pharmacokinetics , Graphite/chemistry , Graphite/pharmacokinetics , Humans , Magnetite Nanoparticles/chemistry , Microscopy, Confocal , Models, Molecular , Nylons/chemistry , Nylons/pharmacokinetics , Optical Imaging
4.
Chem Commun (Camb) ; 48(48): 6034-6, 2012 Jun 18.
Article in English | MEDLINE | ID: mdl-22576270

ABSTRACT

This communication reports a unique way to tune the first order NLO properties of nanoparticles tremendously via organized assembly structures, through σ-bond conjugation.

5.
J Mol Model ; 18(5): 1969-81, 2012 May.
Article in English | MEDLINE | ID: mdl-21877152

ABSTRACT

A combinatorial screening procedure was used for the selection of polymer precursors in the preparation of molecularly imprinted polymer (MIP), which is useful in the detection of the air pollution marker molecule benzo[a]pyrene (BAP). Molecular imprinting is a technique for the preparation of polymer materials with specific molecular recognition receptors. The preparation of imprinted polymers requires polymer precursors such as functional monomer, cross-linking monomer, solvent, an initiator of polymerization and thermal or UV radiation. A virtual library of functional monomers was prepared based on interaction binding scores computed using HyperChem Release 8.0 software. Initially, the possible minimum energy conformation of the monomers and BAP were optimized using the semi-empirical (PM3) quantum method. The binding energy between the functional monomer and the template (BAP) was computed using the Hartree-Fock (HF) method with 6-31 G basis set, which is an ab initio approach based on Moller-Plesset second order perturbation theory (MP2). From the computations, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA) were selected for preparation of BAP imprinted polymer. The larger interaction energy (ΔE) represents possibility of more affinity binding sites formation in the polymer, which provides high binding capacity. The theoretical predictions were complimented through adsorption experiments. There is a good agreement between experimental binding results and theoretical computations, which provides further evidence of the validity of the usefulness of computational screening procedures in the selection of appropriate MIP precursors in an experiment-free way.


Subject(s)
Air Pollutants, Occupational/chemistry , Benzo(a)pyrene/chemistry , Methacrylates/chemistry , Models, Chemical , Polymers/chemistry , Adsorption , Binding Sites , Combinatorial Chemistry Techniques , Computer Simulation , Kinetics , Libraries, Digital , Molecular Imprinting , Reproducibility of Results , Thermodynamics , Ultraviolet Rays
6.
J Nanosci Nanotechnol ; 9(9): 5441-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19928240

ABSTRACT

Molecularly imprinted polymers (MIPs) were synthesized using co-polymerization of methacrylic acid with cross-linking agent ethylene glycol dimethacrylate in the presence of benzo(alpha)pyrene (BAP) followed by the extraction of BAP from cross-linked polymer matrix. The MIP formed by this way contains nanopores, which are geometrically specific to the BAP molecule. BAP belongs to one of the carcinogenic airborne atmospheric pollutants. Morphological characteristics of MIP showed presence of nanopores with an average pore diameter of 27.19 A and Brunauer-Emmett-Teller (BET) surface area of 827.87 +/- 1.63 m2g(-1). The adsorption capacity of BAP onto MIP was determined using equilibrium experiments. The cross-reactivity (CR) experiments were also conducted to found selectivity of BAP in the presence of 5 other polyaromatic hydrocarbon (PAH) compounds. The selectivity factors were calculated for MIP, based on experimental data derived from CR studies. It was found that the PAH molecules smaller being in molecular length (pyrene) than BAP, showed higher interference (up to 40%) compared with other PAH compounds. By increasing the concentration of other PAH compounds (100 microg mL(-1)), the selectivity (alpha) of MIP was reduced from 3.5 to 1.6. The value of equilibrium binding constant for BAP, K(E) = 0.236 microg mL(-1), was larger than other PAH compounds (K(E) values range from 0.011 to 0.028 microg mL(-1)). These properties demonstrate that MIP prepared shows greater binding capacity and selectivity due to creation of homogenous nanopores patterned uniformly in the polymer matrix. This method of preparation of ordered materials at micro and nano-scale are useful in the field of nanodevices and sensors for environmental, defense and biomedical applications.


Subject(s)
Benzo(a)pyrene , Molecular Imprinting , Adsorption , Polymerization , Polymers/chemistry , Solid Phase Extraction
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