PubMed Health⌕ Search

Biomedical subjects

Mark W Grinstaff

Publications and source records attributed to Mark W Grinstaff.

At least 19 recordsLinked to original sources
PubMed2006

Dendrimer-encapsulated camptothecins: increased solubility, cellular uptake, and cellular retention affords enhanced anticancer activity in vitro.

A biocompatible polyester dendrimer composed of the natural metabolites, glycerol and succinic acid, is described for the encapsulation of the antitumor camptothecins, 10-hydroxycamptothecin and 7-butyl-10-aminocamptothecin. The cytotoxicity of the dendrimer-drug complex toward four different human cancer cell lines [human breast adenocarcinoma (MCF-7), colorectal adenocarcinoma (HT-29), non-small cell lung carcinoma (NCI-H460), and glioblastoma (SF-268)] is also reported, and low nmol/L IC(50) values are measured. Cellular uptake and efflux measurements in MCF-7 cells show an increase of 16-fold for cellular uptake and an increase in drug retention within the cell when using the dendrimer vehicle.

Antineoplastic Agents, Phytogenic↗
PubMed2006

Probing the electronic structure of platinum(II) chromophores: crystal structures, NMR structures, and photophysical properties of six new bis- and di- phenolate/thiolate Pt(II)diimine chromophores.

A general route for synthesis of six structurally similar Pt(II) diimine thiolate/phenolates chromophores possessing bulky phenolate or thiolate ligands is reported. The Pt chromophores were characterized using an array of techniques including 1H, 13C, and 195Pt NMR, absorption, emission, (spectro)electrochemistry, and EPR spectroscopy. Systematic variation of the electronic structure of the Pt(II) chromophores studied was achieved by (i) changing solvent polarity; (ii) substituting oxygen for sulfur in the donor ligand; (iii) alternating donor ligands from bis- to di-coordination; and (iv) changing the electron donating/withdrawing properties of the ligand(s). The lowest excited state in these new chromophores was assigned to a [charge-transfer-to-diimine] transition from the HOMO of mixed Pt/S (or Pt/O) character on the basis of absorption and emission spectroscopy, UV/vis (spectro)electrochemistry, and EPR spectroscopy. One of the chromophores, Pt(dpphen)(3,5-di-tert-butyl-catecholate) represents an example of a Pt(II) diimine phenolate chromophore that possesses a reversible oxidation centered predominantly on the donor ligand. Results from EPR spectroscopy indicate participation of the Pt(II) orbitals in the HOMO. There is a dramatic difference in the photophysical properties of carborane complexes compared to other mixed-ligand Pt(II) compounds, which includes room-temperature emission and photostability. The charge-transfer character of the lowest excited state in this series of chromophores is maintained throughout. Moreover, the absorption and emission energies and the redox properties of the excited state can be significantly tuned.

Crystallization↗
PubMed2006

Self-assembled microspheres from f-block elements and nucleoamphiphiles.

Hollow microspheres featuring a hybrid lipid-cation multilamellar shell are prepared by hydration of a nucleoside based amphiphile with an aqueous solution containing either actinide or lanthanide salts. The physico-chemical data collected clearly indicate that the formation of these microspheres is a consequence of the following concomitant stabilizing factors: (i) hydrophobic interactions, (ii) nucleobase dimer formation and (iii) phosphate/f-block element salt binding.

Actinoid Series Elements↗
PubMed2006

Peptide-PEG amphiphiles as cytophobic coatings for mammalian and bacterial cells.

Amphiphilic macromolecules containing a polystyrene-adherent peptide domain and a cell-repellent poly(ethylene glycol) domain were designed, synthesized, and evaluated as a cytophobic surface coating. Such cytophobic, or cell-repellent, coatings are of interest for varied medical and biotechnological applications. The composition of the polystyrene binding peptide domain was identified using an M13 phage display library. ELISA and atomic force spectroscopy were used to evaluate the binding affinity of the amphiphile peptide domain to polystyrene. When coated onto polystyrene, the amphiphile reduced cell adhesion of two distinct mammalian cell lines and pathogenic Staphylococcus aureus strains.

Amino Acid Sequence↗
PubMed2006

Biodendrimer-based hydrogel scaffolds for cartilage tissue repair.

Photo-crosslinkable dendritic macromolecules are attractive materials for the preparation of cartilage tissue engineering scaffolds that may be optimized for in situ formation of hydrated, mechanically stable, and well-integrated hydrogel scaffolds supporting chondrocytes and chondrogenesis. We designed and synthesized a novel hydrogel scaffold for cartilage repair, based on a multivalent and water-soluble tri-block copolymer consisting of a poly(ethylene glycol) core and methacrylated poly(glycerol succinic acid) dendrimer terminal blocks. The terminal methacrylates allow mild and biocompatible photo-crosslinking with a visible light, facilitating in vivo filling of irregularly shaped defects with the dendrimer-based scaffold. The multivalent dendrimer constituents allow high crosslink densities that inhibit swelling after crosslinking while simultaneously introducing biodegradation sites. The mechanical properties and water content of the hydrogel can easily be tuned by changing the biodendrimer concentration. In vitro chondrocyte encapsulation studies demonstrate significant synthesis of neocartilaginous material, containing proteoglycans and type II collagen.

Animals↗
PubMed2005

Synthesis and aqueous aggregation properties of amphiphilic surface-block dendrimers.

[reaction: see text] A family of dendritic amphiphiles were synthesized from the natural metabolites of glycerol, succinic acid, and myristic acid. The surfaces of these dendrimers display different numbers of alkyl chains and carboxylic acids, varying the hydrophobic-to-hydrophilic ratio over a relatively broad range. In solution these dendritic amphiphiles form supramolecular structures, and these aggregates have been characterized by light microscopy, transmission electron microscopy, and tensiometry. These aggregates can entrap the hydrophobic species pyrene.

Dendrimers↗
PubMed2005

Nucleoside phosphocholine amphiphile for in vitro DNA transfection.

A new transfection reagent based on nucleoside phosphocholine amphiphile leading to high transfection efficacy and low cytotoxicity is described. TEM, ethidium bromide displacement assays, agarose gel electrophoresis and SAXS studies support the formation of lipoplexes for the transfection of CHO cells.

Animals↗
PubMed2005

Supramolecular assemblies of DNA with neutral nucleoside amphiphiles.

A neutral uridine-based amphiphile is described which condenses plasmid DNA. AFM studies show that the three distinct structural components of the amphiphile (i.e, nucleobase, alkyl chains, and poly(ethylene glycol)) are required for the formation of DNA-amphiphile supramolecular assemblies on a mica surface.

DNA↗
PubMed2005

Novel tissue adhesives to secure laser in situ keratomileusis flaps.

PURPOSE: To evaluate 2 novel biodendrimer tissue adhesives in sealing and securing laser in situ keratomileusis (LASIK) flaps. SETTING: Duke University Eye Center, Durham, North Carolina, USA. METHODS: Laser in situ keratomileusis flaps were created in 10 human eye-bank eyes using the Hansatome microkeratome system (Bausch & Lomb). These eyes were divided into 2 groups. Flaps in the first group (n=4) were secured with a laser-activated biodendrimer adhesive along the flap edge. In the second group (n=6), the flaps were secured with a self-gelling dendritic adhesive. Dry Merocel sponges (Medtronic Solan) were used to test the strength of flap adherence in both groups. Further testing was performed in the second group. The hinges of these flaps were cut with a scalpel blade and fluorescein dye was injected under the flap to observe potential dye leakage along the flap edge. RESULTS: Laser in situ keratomileusis flaps sealed with both adhesives were secure with no flap dislocation. There was no leakage of fluorescein dye observed in the second group. Both adhesives were easy to apply, clear when dry, and had a soft rubbery consistency. CONCLUSIONS: Two novel biodendrimer adhesives successfully sealed and secured LASIK flaps. These adhesives may prove to be an effective alternative for treating LASIK flap complications such as epithelial ingrowth or flap dislocation.

Corneal Stroma↗
PubMed2004

Dendritic macromers as in situ polymerizing biomaterials for securing cataract incisions.

Dendritic macromers are attractive macromolecules for hydrogel formation since high cross-linking densities at low polymer concentration can be obtained, varied physical properties can be observed based on the macromer structure, and low viscous aqueous solutions can be injected in an in vivo site of irregular shaped to form a well-integrated polymer network. A peptide dendron possessing terminal cysteine residues was synthesized and characterized. When this peptide dendron was mixed with poly(ethylene glycol dialdehyde) in aqueous solution at pH = 7.4, a hydrogel spontaneously formed as a consequence of thiazolidine linkages between the macromers. Such in situ polymerized hydrogels are of interest for tissue engineering and wound-repair applications. To evaluate the potential use of this hydrogel sealant in ophthalmic surgeries, a 3-mm clear corneal incision (i.e., the wounds created during a typical cataract surgery) was successfully sealed.

Biocompatible Materials↗
PubMed2004

Charge-reversal amphiphiles for gene delivery.

Delivering a missing gene or a functional substitute of a defective gene has the potential to revolutionize current medical care. Of the two gene delivery approaches, viral and synthetic vectors, synthetic cationic vectors possess several practical advantages but suffer from poor transfection efficiency. A new approach to gene delivery using charge-reversal amphiphiles is described. This synthetic vector transforms from a cationic to an anionic amphiphile intracellularly. This amphiphile performs two roles: first, it binds and then releases DNA, and second, as an anionic multicharged amphiphile, it destabilizes lipid bilayers. A charge-reversal amphiphile was synthesized and fully characterized, including the supramolecular complex it forms with DNA. Enhanced gene transfection was observed using these vectors compared to current cationic amphiphiles.

Animals↗
PubMed2004

DNA-PEG-DNA triblock macromolecules for reagentless DNA detection.

The sandwich assay is the most common design for electrochemical DNA sensors. This assay consists of three individual DNA components: an immobilized capture strand, a target strand, and a probe strand containing a redox-active reporter group. We report a simplified DNA assay where two strands of ssDNA, the capture and probe strands, are linked together via a flexible poly(ethylene glycol) (PEG) spacer forming an ABA triblock macromolecule. We have developed an electrochemical assay where the detection signal arises as a consequence of a large structural change induced upon hybridization with target DNA. In this system, the DNA-PEG-DNA macromolecule folds or wraps around the target DNA, bringing the ferrocene probe in close proximity to the electrode, affording an electrochemical response.

DNA↗
PubMed2004

Conformationally gated electrochemical gene detection.

The synthesis and characterization of a 26-base DNA hairpin containing both a redox-active reporter (ferrocene) and terminal thiol functionality for electrochemical gene detection is described. This electrochemical DNA sensor exploits electron-transfer dynamics that alter as a consequence of a large structural rearrangement (hairpin-to-duplex) induced by hybridization of the target DNA sequence. Melting temperature and circular dichroism studies confirm that the 26-mer DNA forms a hairpin structure in the absence of target DNA. The loop region of the DNA hairpin is shown to form a stable duplex in the presence of complementary single-stranded DNA. Atomic force microscopy and ellipsometry experiments of immobilized self-assembled DNA monolayers suggest that hybridization with complementary DNA affords a conformational change that alters the electrochemical response.

Base Sequence↗
PubMed2004

Supramolecular assemblies of nucleoside phosphocholine amphiphiles.

A family of new uridine phosphocholine amphiphiles that were prepared using a convenient four-step synthetic route is described. Physicochemical studies (differential scanning calorimetry, small-angle X-ray scattering, UV-vis and circular dichroism spectroscopies, light microscopy, transmission electronic microscopy, and scanning electron microscopy) show that these amphiphiles spontaneously assemble into supramolecular structures including vesicles, fibers, hydrogels, and organogels. In aqueous solution, the amphiphiles possessing saturated alkyl chains self-assemble into DNA-like helical fibers in the crystalline state below T(m) and compact bilayers above the melting temperature (T(m)). The transition from bilayers to fibers is thermally reversible. Above a threshold concentration (>6% w/w), a hydrogel is formed due to an entangled network of the fibers. A therapeutic agent such as DNA can be entrapped within the hydrogel structure. In addition to forming bilayer vesicles and hydrogels in aqueous solution, these nucleoside amphiphiles also form organogels in cyclohexane above T(m). Scanning electron microscopy shows a continuous multilamellar phase in the organogels.

Animals↗
PubMed2004

New dendritic adhesives for sutureless ophthalmic surgical procedures: in vitro studies of corneal laceration repair.

OBJECTIVE: To compare a biodendrimer adhesive with a conventional suture for repairing linear and stellate corneal lacerations. METHODS: A keratome knife was used to create 4.1-mm full-thickness linear incisions (n = 36) and 3 x 4-mm full-thickness stellate incisions (n = 25) in the central cornea of enucleated human eyes. The incisions were sealed with either a suture or the biodendrimer adhesive. The globes were inflated with balanced salt solution, and the increase in intraocular pressure was monitored via a cardiac transducer until fluid leaked from each eye. This intraocular pressure reading from the transducer was recorded at the sight of any leakage through the wound (leakage pressure). By using the Wilcoxon rank sum test, the median leakage pressure was compared for each closure method, separately for each wound group. By using the 1-sided 1-sample t test, each mean leakage pressure value was compared with 34 mm Hg, which is the intraocular pressure under certain stressful physiologic conditions (eg, coughing and the Valsalva maneuver). RESULTS: For globes that underwent a linear incision, the mean leakage pressure was 78.7 mm Hg for the sutured group and 109.6 mm Hg for the adhesive group. Globes that underwent a stellate incision had a mean leakage pressure of 57.8 mm Hg for the sutured group and 78.7 mm Hg for the adhesive group. All of these pressures showed a statistical significance from 34 mm Hg via a 1-sided 1-sample t test. CONCLUSIONS: The difference in leakage pressures for all 4 groups was statistically significant relative to 34 mm Hg. This suggests that either method of closure, adhesive or suture, can withstand physiologic increases in intraocular pressure postoperatively and that biodendrimer adhesives are able to seal large corneal lacerations.Clinical Relevance The use of biodendrimer adhesives to repair a corneal wound constitutes a viable alternative clinical procedure to conventional sutures.

Biocompatible Materials↗
PubMed2004

Photocrosslinkable hyaluronan as a scaffold for articular cartilage repair.

Hyaluronan-based scaffolds are of interest for tissue-engineered cartilage repair due to an important role for hyaluronan in cartilage development and function. In this study, an in situ photocrosslinkable hyaluronan (HA-MA) was developed and evaluated as a scaffold for articular cartilage repair. Chondrocytes were encapsulated in crosslinked HA-MA and evaluated for their ability to synthesize cartilaginous matrix in vitro. The mechanical and physical properties of the crosslinked HA-MA hydrogels were similar to that of other hydrogels, with compressive and dynamic shear moduli of 0.6 and 0.3 kPa, respectively, and diffusion coefficients of 600-8000 microm2/s depending on molecular weight. Chondrocytes remained rounded in the HA-MA hydrogels in vitro, and accumulated significant amounts of cartilaginous matrix. Osteochondral defects filled with HA-MA were infiltrated with cells, appeared to integrate well with native tissue, and also accumulated substantial cartilaginous matrix by 2 weeks after surgery. In summary, photocrosslinkable HA-MA promoted the retention of the chondrocytic phenotype and cartilage matrix synthesis for encapsulated chondrocytes in vitro and accelerated healing in an in vivo osteochondral defect model.

Animals↗