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Biomedical subjects

Mark W Grinstaff

Publications and source records attributed to Mark W Grinstaff.

34 records · Page 2Linked to original sources
PubMed2003

Dendritic molecular capsules for hydrophobic compounds.

Reichardt's dye, a highly solvatochromic dye, was encapsulated within poly (glycerol succinic acid) ([Gn]-PGLSA-OH) dendrimers to investigate the interior environment of these dendritic macromolecules. The absorption maximum for the encapsulated Reichardt's dye in water was indicative of a relatively high dielectric constant present within the dye/dendrimer complex. (1)H NMR of the encapsulated complex showed the presence of aromatic protons from Reichardt's dye along with the aliphatic protons of the dendrimer. Additionally, there were substantial changes in T(1) and T(2) times of the encapsulated dye when compared with the free dye, and (1)H NOESY spectra for the complex showed a significant number of intermolecular NOE cross-peaks. These data reveal the close through-space proximity of the dye to the dendrimer and the restricted motion of the encapsulated dye. To demonstrate the potential use of these macromolecules as drug delivery vehicles, the poorly water-soluble anticancer drug 10-hydroxycamptothecin (10HCPT) was encapsulated within a carboxylated PGLSA dendrimer ([G4]-PGLSA-COONa). Cytotoxicity assays with human breast cancer cells showed a significant reduction of cell viability, demonstrating that 10HCPT retains activity upon encapsulation.

Benzene Derivatives↗
PubMed2003

The convergent synthesis of poly(glycerol-succinic acid) dendritic macromolecules.

The high-yield convergent synthesis of dendrons, dendrimers, and dendritic-linear hybrid macromolecules composed of succinic acid, glycerol, and poly(ethylene glycol) (PEG) is described. This convergent synthesis relies on two orthogonal protecting groups; namely, the benzylidene acetal (bzld) for the protection of the 1,3-hydroxyls of glycerol and the tert-butyldiphenylsilyl (TBDPS) ester for protection of the carboxylic acid of succinic acid. These novel polyester dendritic macromolecules are composed entirely of building blocks known to be biocompatible or degradable in vivo to give natural metabolites. Derivatization of the dendritic periphery with a methacrylate affords a polymer that can be subsequently photo-cross-linked. The three-dimensional cross-linked gels formed by ultraviolet irradiation are optically transparent, with mechanical properties dependent on the initial cross-linkable dendritic macromolecule.

Biocompatible Materials↗
PubMed2003

Intramolecular electrocatalysis of 8-oxo-guanine oxidation: secondary structure control of electron transfer in osmium-labeled oligonucleotides.

A phosphoramidite containing Os(bpy)(3)(2+) (Os; bpy, 2,2'-bipyridine) with a three-carbon linker was synthesized and used to prepare oligonucleotides with the Os redox catalyst appended to the 5'-end. The electrogenerated Os(III) is capable of oxidizing 7,8-dihydro-8-oxo-guanine (8G), but 8G is not electrochemically reactive at indium tin oxide electrodes because of poor electrode kinetics for the direct reaction. The hairpin-forming oligonucleotide Os-5'-ATG TCA GAT TAG CAG GCC TGA CAT 8G was synthesized and characterized by thermal denaturation and native gel electrophoresis both in the hairpin form and when hybridized to its Watson-Crick complement. The redox potential in both forms of the appended Os(III/II) couple was 0.63 V (all potentials vs Ag/AgCl), which is identical to that for the free complex. The diffusion coefficients of the hairpin form (10.2 x 10(-)(7) cm(2)/s) and the duplex form (8.7 x 10(-)(7) cm(2)/s) were consistent with values expected from studies of noncovalently bound redox labels, which suggest that the measured diffusion coefficient should be that of the appended DNA molecule. The oligonucleotide was designed such that in the duplex form, the 8G is far from the Os(III/II) couple, but in the hairpin form, the 8G is situated close to the redox center. For the duplex form, cyclic voltammetry studies showed that mediated oxidation of the 8G nucleobase occurred only through bimolecular reaction of the electrogenerated Os(III) of one duplex with the 8G of another duplex. However, in the hairpin form, intramolecular electron transfer from 8G to Os(III) in the same molecule was apparent in both chronoamperometry and cyclic voltammetry.

Catalysis↗
PubMed2003

Engineering porcine arteries: effects of scaffold modification.

Techniques have been developed to culture bovine or porcine vascular cells on polyglycolic acid (PGA) scaffolds to form engineered vessels. Previously, it was shown that smooth muscle cells (SMCs) that were in close proximity to PGA remnants after 8 weeks of culture had lower expression of SMC markers of differentiation and were more mitotic compared with SMCs that were distant from polymer residuals. Modifications of PGA were explored as a means to minimize residual polymer fragments after culture. To hasten degradation, polymer was treated with heat, NaOH, or gamma-irradiation. Differential scanning calorimetry, mass and tensile strength degradation, and inherent viscosity were used to assess polymer characteristics. When polymer was maintained in aqueous conditions, tensile strength of treated PGA degraded to zero within 3 weeks for each treatment. Engineered vessel constructs cultured on NaOH and gamma-treated polymer displayed smooth muscle alpha-actin throughout the vessel wall. Scaffold treatment impacted graft morphology, cellular differentiation, and mechanical integrity.

Animals↗
PubMed2002

Synthesis and characterization of pi-stacked phenothiazine-labeled oligodeoxynucleotides.

[reaction: see text] A facile procedure for the incorporation of N-methyl phenothiazine as the terminal nucleoside in oligodeoxynucleotides is reported. The phenothiazine nucleoside analogue is synthesized and then incorporated into DNA using an automated DNA solid-phase synthesizer. Phenothiazine-labeled oligodeoxynucleotides form stable B-form duplexes with higher melting temperatures compared to unlabeled DNA duplexes.

Combinatorial Chemistry Techniques↗
PubMed2002

Biodendrimers: new polymeric biomaterials for tissue engineering.

Dendrimers composed entirely of building blocks known to be biocompatible or degradable in vivo to natural metabolites were synthesized using a high yield divergent approach. This synthesis is amenable to the design and development of new biomaterials that are of interest for a variety of medical applications, including tissue engineering. In a novel application, photocross-linkable dendrimers are used to seal large corneal lacerations.

Biocompatible Materials↗
PubMed2002

Synthesis and characterization of carbohydrate-based phospholipids.

Novel carbohydrate-based phospholipids containing two saturated C(12) (dilauroyl ribo-phosphocholine) (DLRPC), C(14) (dimyristoyl ribo-phosphocholine) (DMRPC), and C(20) (diarachadonyl ribo-phosphocholine) (DARPC) carboxylic acid chains were synthesized. The physical properties of the supramolecular structures formed by these compounds were compared to those formed by their direct glycerol analogues dilauroyl phosphocholine (DLPC), dimyristoyl phosphocholine (DMPC), and diarachadonyl phosphocholine (DAPC). Modulated differential scanning calorimetry (MDSC) and X-ray diffraction data indicated that with chain lengths < or =14 carbons, the carbohydrate backbone increased the thermal stability of the bilayer below the phase-transition temperature (T(m)) as compared to the glycerol-based lipids. With longer chains (C(20)), the bilayer structure was destabilized as compared to glycerol-based lipids. NMR studies of a DMRPC vesicle dispersion reveal split choline headgroup signals and distinct magnetization transfer effects arising from the "inner" and "outer" surfaces of the bilayer vesicle. Modulated differential scanning calorimetry also demonstrated that glycerol- and carbohydrate-based lipids mix, as evidenced by a single intermediate T(m). In addition, carbohydrate-based lipid/cholesterol mixtures exhibited a decrease in enthalpy with an increase in cholesterol concentration. Unlike glycerol phospholipids, carbohydrate lipids were resistant to enzymatic degradation by phospholipase A(2) (PLA(2)).

Calorimetry, Differential Scanning↗
PubMed2002

Hybrid dendritic-linear polyester-ethers for in situ photopolymerization.

Novel first through fourth generation hybrid dendritic-linear copolymers, composed entirely of building blocks known to be biocompatible or degradable to natural metabolites in vivo, are described. Specifically, these copolymers are composed of poly(ethylene glycol), glycerol, and succinic acid and are synthesized using a divergent approach in high yield. A photo-cross-linkable derivative of this copolymer successfully seals 4.1 mm corneal lacerations. The mechanism of tissue repair is likely one of physical entrapment where an interpenetrating network (IPN) is formed between the cross-linked copolymer and the tissue.

Eye Injuries↗
PubMed2002

Direct-writing of polymer nanostructures: poly(thiophene) nanowires on semiconducting and insulating surfaces.

A new technique for direct-writing of polymer nanostructures on insulating and semiconducting surfaces based on Electrochemical Dip-Pen Nanolithography (E-DPN) is described. The technique is based on electrochemical polymerization of monomers directly underneath the AFM tip. Sub-50 nm poly-3,4-ethylenedioxythiophene lines can be easily created. Such capability to direct-write and pattern polymeric materials with interesting electronic and electrooptical properties at the nanoscale creates a number of opportunities since a large variety of monomers are available.

Journal Article↗
PubMed2002

Synthesis and characterization of a dianionic carbohydrate-based phospholipid.

A novel carbohydrate-based phospholipid containing a phosphatidic acid head group, bis-(2,3-lauroyl)-1-methoxy-5-ribo-phosphatidic acid (DLRPA), was synthesized and characterized by 1H NMR, 13C NMR, and 31P NMR. This molecule is an analog of dilauroyl phosphatidic acid (DLPA). The T(m) of DLRPA decreases with increasing pH in a similar pattern to DLPA, as determined by MDSC. From this thermotropic behavior, the apparent pK(a)s of DLRPA are estimated to be 4 and 8.

Anions↗
PubMed2002

A photopolymerized sealant for corneal lacerations.

PURPOSE: To determine whether a novel photocrosslinkable polymer synthesized from hyaluronic acid would seal experimental full-thickness corneal lacerations in a rabbit model. METHODS: A solution of hyaluronic acid was modified with methacrylate groups (HA-MA), precipitated, dried, reconstituted in an aqueous solution, and sterilized before use. The viscous polymer solution was applied to 38 of 43 experimental corneal lacerations in rabbits and subsequently irradiated with a low-intensity argon laser beam to produce a clear flexible polysaccharide hydrogel patch. The ability of this sealant to repair corneal lacerations was evaluated in four types of full-thickness, 3-mm corneal wounds (linear, linear + epithelium removed, stellate, and stellate + epithelium removed). Slit-lamp examinations, measurements of intraocular pressure, Seidel tests, and histologic studies were performed at selected intervals to evaluate the wound and determine the rate of healing. RESULTS: Corneal perforations were completely sealed and the anterior chambers had reformed by 6 hours in HA-MA-treated eyes. There was no evidence of leakage at this or later times in 37 of the 38 eyes. Intraocular pressure had risen to near-normal levels by day 7 in all four groups, and the sealant was still present in most eyes at day 7. In contrast, the anterior chambers did not re-form in control eyes (five) with untreated perforations because of aqueous leakage through the wounds. Minimal inflammation was observed clinically or in histologic sections of treated corneas. There was extensive proliferation of stromal cells and formation of new extracellular matrix at the wound edges, which became tightly adherent between days 4 and 7. CONCLUSION: Our novel photocrosslinkable methacrylated hyaluronan polymer sealed 97% (37/38) of the experimental corneal lacerations. HA-MA may prove useful for sealing corneal lacerations in patients and for other sutureless ophthalmic surgical procedures.

Animals↗
PubMedDate not supplied

Synthesis and characterization of phenothiazine labeled oligodeoxynucleotides: novel 2'-deoxyadenosine and thymidine probes for labeling DNA.

A facile procedure for the incorporation of phenothiazine at the terminus of oligodeoxynucleotides is reported. Phenothiazine is covalently linked to the 5'-position of 2'-deoxyadenosine and thymidine. Next, the corresponding phosphoramidites are prepared, and then the labeled nucleosides are incorporated in DNA using an automated DNA solid-phase synthesizer. Phenothiazine labeled oligodeoxynucleotides form stable B-form duplexes with similar melting temperatures, CD spectra, and DSC traces compared to unlabeled DNA duplexes. The favorable photophysical properties of phenothiazine are also retained after covalent attachment to the oligodeoxynucleotide.

Affinity Labels↗
PubMedDate not supplied

Nucleic acid complexing glycosyl nucleoside-based amphiphile.

A neutral amphiphile derived from uridine featuring two oleyl chains and one glucose for DNA binding was prepared using a convenient four-step synthetic route. The nucleic acid binding capabilities of this amphiphile were investigated by UV-vis, quasi-elastic light scattering (QELS), transmission electronic microscopy (TEM), gel electrophoresis, 31P NMR, IR, and circular dichroism (CD). Amphiphile-nucleic acid complex formation is a consequence of the amphiphilic character of the molecule, phosphate-sugar, and nucleobase-nucleobase interactions. This work presents for the first time a glyco-nucleo-amphiphile capable of binding efficiently the nucleic acid double helix structure.

Animals↗
PubMedDate not supplied

Cationic nucleoside lipids for gene delivery.

A novel uridine-based nucleo-lipid, DOTAU (N-[5'-(2',3'-dioleoyl)uridine]-N',N',N'-trimethylammonium tosylate) was prepared by using a convenient four-step synthetic pathway. From the preliminary physicochemical studies (quasielastic light scattering and light microscopy), this amphiphilic structure forms supramolecular organizations in aqueous solution. In addition, in the presence of nucleic acids, transmission electronic microscopy experiments (TEM) and small angle X-ray scattering (SAXS) reveal the formation of multilamellar structures similar to lipoplexes (cationic liposome-DNA complexes) with cationic lipids. The formation of a complex was confirmed by fluorescence spectroscopic assays involving ethidium bromide. Transfection assays of mammalian cell lines (HeLa and MCF-7) indicate that DOTAU can transfect efficiently an expression vector (pEGFP) encoding GFP. Proliferation assays realized on these cell lines show that DOTAU does not inhibit cell proliferation and is less toxic than the commercial Lipofectamine 2000.

Cations↗
PubMedDate not supplied

Hydrogels formed by multiple peptide ligation reactions to fasten corneal transplants.

A stable cross-linked hydrogel was formed under mild aqueous conditions using pseudoproline peptide ligation chemistry. A cysteine-terminated lysine dendron containing four cysteines and a PEG macromolecule modified with terminal ester aldehydes were prepared. Upon mixing, the two macromers gave a stable hydrogel. This hydrogel along with sutures was used to successfully secure a corneal transplant in vitro.

Corneal Transplantation↗