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Biomedical subjects

Hak Soo Choi

Publications and source records attributed to Hak Soo Choi.

15 recordsLinked to original sources
PubMed2006

Image-guided oncologic surgery using invisible light: completed pre-clinical development for sentinel lymph node mapping.

BACKGROUND: Invisible near-infrared (NIR) fluorescent light permits high sensitivity, real-time image-guidance during oncologic surgery without changing the look of the surgical field. In this study, we complete pre-clinical development of the technology for sentinel lymph node (SLN) mapping using a large animal model of spontaneous melanoma. METHODS: Sinclair swine with spontaneous melanoma metastatic to regional lymph nodes were used because of their similarity to human melanoma. Organic lymphatic tracers tested included FDA-approved indocyanine green adsorbed non-covalently to human serum albumin (HSA), and NIR fluorophore CW800 conjugated covalently to HSA (HSA800). The inorganic/organic hybrid tracer tested was type II NIR quantum dots with an anionic coating. Primary tumors received four peri-tumoral injections of each tracer, with a fluorophore dose of 100 pmol to 1 nmol per injection. SLN mapping and image-guided resection were performed in real-time. RESULTS: Each of the 3 lymphatic tracers was injected into n = 4 separate primary melanomas in a total of 6 animals. All 12 injections resulted in identification of the SLN(s) and their associated lymphatic channels within 1 minute in 100% of cases, despite highly pigmented skin and black fur. Hydrodynamic diameter had a profound impact on tracer behavior in vivo. CONCLUSIONS: This study completes the pre-clinical development of NIR fluorescence-guided SLN mapping and provides insight into imaging system optimization and tracer choice for future human clinical trials. The technology is likely to eliminate the need for radioactive and colored tracers, permits real-time image guidance throughout the procedure, and assists the pathologist in tissue analysis.

Animals↗
PubMed2006

pH-responsive movement of cucurbit[7]uril in a diblock polypseudorotaxane containing dimethyl beta-cyclodextrin and cucurbit[7]uril.

[Structure: see text] A polypseudorotaxane consisting of cucurbit[7]uril (CB[7])/N,N'-(3-phenylenebis(methylene)dipropargylamine (PMPA), [2]pseudorotaxane, and 2,6-O-dimethyl beta-cyclodextrin (DM-beta-CD)/alpha,omega-bisazidopropylene glycol 400 [2]pseudorotaxane was synthesized using the "click" reaction. The polypseudorotaxane structure was maintained in aqueous solution over a wide range of pH values with the DM-beta-CD units contributing to increased solubilization of the polypseudorotaxane without dethreading. The pH-responsive movement of the CB[7] units in the polypseudorotaxane was also observed.

Bridged-Ring Compounds↗
PubMed2006

One-pot synthesis of a polyrotaxane via selective threading of a PEI-b-PEG-b-PEI copolymer.

A functional polyrotaxane of a PEI-b-PEG-b-PEI copolymer is synthesized in aqueous solution in a one-pot sequence. To obtain a polyrotaxane with PEG-block-selective inclusion complexes, the solution pH of the polypseudorotaxane is lowered to 4.4 in the presence of 9-anthraldehyde (AN), which triggers the expulsion of the alpha-cyclodextrins (alpha-CDs) from the flank PEI chains. Synthetic strategy of a block-selective polyrotaxane between a PEI-b-PEG-b-PEI copolymer and alpha-cyclodextrins.

Anthracenes↗
PubMed2006

Biocleavable polyrotaxane-plasmid DNA polyplex for enhanced gene delivery.

A biocleavable polyrotaxane, having a necklace-like structure consisting of many cationic alpha-cyclodextrins (alpha-CDs) and a disulfide-introduced poly(ethylene glycol) (PEG), was synthesized and examined as a nonviral gene carrier. The polyrotaxane formed a stable polyplex having positively charged surface even at low charge ratio. This is likely to be due to structural factors of the polyrotaxane, such as the mobile motion of alpha-CDs in the necklace-like structure. Rapid endosomal escape was observed 90 min after transfection. The positively charged surface and the good buffering capacity are advantageous to show the proton sponge effect. The pDNA decondensation occurred through disulfide cleavage of the polyrotaxane and subsequent supramolecular dissociation of the noncovalent linkages between alpha-CDs and PEG. Transfection of the DMAE-SS-PRX polyplex is independent of the amount of free polycation. Those properties played a key role for delivery of pDNA clusters to the nucleus. Therefore, the polyplex nature and the supramolecular dissociation of the polyrotaxane contributed to the enhanced gene delivery.

Cell Nucleus↗
PubMed2006

Improved cell viability of linear polyethylenimine through gamma-cyclodextrin inclusion for effective gene delivery.

A polypseudorotaxane consisting of a linear polyethylenimine with Mn of 22,000 (LPEI22k) and gamma-cyclodextrins (gamma-CDs; LPEI22k/gamma-CD) has been examined as a gene carrier. The polyplex formation with luciferase-encoding plasmid DNA (pDNA), intracellular trafficking of polyplex, cytotoxicity, and transfection efficiency were evaluated by various characteristic methods. LPEI22k/gamma-CD formed a pDNA polyplex at higher N/P ratios than LPEI22k; this suggests that the gamma-CD threading sterically interfered with the polyplex formation. In addition, the zeta potentials of the polyplex significantly decreased due to the reduction in charge density of LPEI22k caused by gamma-CD threading. The cellular uptake of pDNA in the LPEI22k/gamma-CD polyplex was enhanced by free gamma-CDs released from the polyplex that might accelerate the cellular uptake through enhanced membrane affinity. LPEI22k/gamma-CD significantly increased cell viability even at high N/P ratios, and the polyplex showed high transfection efficacy. The low cytotoxicity and high gene expression of LPEI22k/gamma-CD are advantageous to polyplex administration in vivo.

Animals↗
PubMed2006

Synthesis, characterization, and pH-triggered dethreading of alpha-cyclodextrin-poly(ethylene glycol) polyrotaxanes bearing cleavable endcaps.

The synthesis, characterization, and degradation kinetics of three alpha-cyclodextrin (alpha-CD)-poly(ethylene glycol) (PEG) polyrotaxanes with endcaps that were installed using Cu(I)-catalyzed Huisgen cyclization is reported. PEG1500, azidated with azidoacetic acid, was threaded with alpha-CD to form a pseudopolyrotaxane that was then capped in up to 82% yield with three different substituents to provide polyrotaxanes that were either acid-, base-, or fluoride-sensitive. NMR, GPC, XRD, and AFM methods were used to characterize the polyrotaxanes. Dethreading rates upon exposure to mild deprotection conditions were monitored by turbidity analysis. The vinyl ether-endcapped polyrotaxane is stable at pH 7 for 16 h but is solubilized at approximately 0.0211 min(-1) at pH 4. The ester-endcapped polyrotaxane is solubilized at 0.0122 min(-1) at pH 12.1. Our results show that pH-triggerable polyrotaxanes can be readily and efficiently prepared from pseudopolyrotaxanes in high yield by Huisgen cyclization of azido- and alkynyl-modified precursors in the presence of Cu(I).

Biocompatible Materials↗
PubMed2005

Synthesis of poly(epsilon-lysine)-grafted dextrans and their pH- and thermosensitive hydrogelation with cyclodextrins.

To give pH sensitivity to a thermoreversible supramolecular-structured hydrogel system, poly(epsilon-lysine) (PL), as a cationic polymer, was grafted to dextran and used for inclusion complexation with alpha-cyclodextrins (alpha-CDs). The synthesized graft copolymer was characterized by 1H NMR spectroscopy, and the hydrogel formation was confirmed by X-ray diffraction and solid-state 13C NMR analysis. The hydrogelation was induced from a phase-separated structure of hydrated dextrans and hydrophobically aggregated inclusion complexes in buffer solution at pH 10.0. The prepared hydrogels showed thermoreversible gel-sol transitions as well as pH-sensitive phase transitions, which were recorded by the changes in UV/Vis transmittance. A rapid phase transition from gel to sol was observed upon decreasing the pH value to 4.0, which resulted from the dissociation process between the protonated guest polymer and alpha-CDs. The stimuli-responsive physical properties of the hydrogels were improved by modulating the degree of substitution of the grafted PL and the combination with alpha-CDs.

Journal Article↗
PubMed2003

pH- and thermosensitive supramolecular assembling system: rapidly responsive properties of beta-cyclodextrin-conjugated poly(epsilon-lysine).

beta-Cyclodextrin-conjugated poly(epsilon-lysine) (beta-CDPL) was synthesized as a novel polymeric host for constructing a smart supramolecular assembling system. Systematic studies on the inclusion complexation between the polymeric host with an alpha- or beta-CD cavity and a model guest molecule provided evidence that dual cooperative interactions, specific host-guest interaction and intermolecular ionic interaction, played a dominant role in leading to a fast aggregation phenomenon. In addition, a rapid phase transition induced by the supramolecular assembly was observed reversibly in response to a small change in pH or temperature.

Biomimetic Materials↗
PubMed2002

A local delivery system for fentanyl based on biodegradable poly(L-lactide-co-glycolide) oligomer.

To obtain a sustained fentanyl delivery with effective and precise control, fentanyl loaded wafer was fabricated using poly(L-lactide-co-glycolide) (PLGA) oligomer by direct compression method. XRD and DSC analysis indicated the presence of crystalline drug in the wafers. The release of fentanyl from PLGA wafer was determined to be primarily diffusion controlled, but swelling and erosion also contributed to the release process. In vitro release studies showed that different release patterns and rates could be achieved by simply modifying factors in the preparation conditions. The wafer degradation profiles were also investigated to understand the drug release mechanism. Gravimetric studies of mass loss of wafers during the incubation revealed that the weight loss increased apparently after 4 days. These results indicate that the polymer degradation was contributed to drug release followed by diffusion. From the results, this constant localized release system can potentially provide anesthesia for a longer period than injection or topical administration.

Analgesics, Opioid↗
PubMed2002

Preparation and characterization of fentanyl-loaded PLGA microspheres: in vitro release profiles.

We developed several kinds of fentanyl-loaded poly(L-lactide-co-glycolide) (PLGA) microspheres (FMS) for sustained release of fentanyl. FMS were prepared by an emulsion solvent-evaporation method. In this study, the influences of several preparation parameters, such as initial drug loading, polymer concentration, and solvent volume on the release patterns of fentanyl were investigated. Furthermore, it has been well noted that the detection of fentanyl is extremely difficult because its clinical dose level is very low, about 1-3 ng/ml, in cancer-patient treatment. Therefore, we also developed a rapid and sensitive determination method for fentanyl in systemic circulation by employing gas chromatography (GC) system. Fentanyl was slowly released from FMS over 15 days with a quasi-zero order property. From the results, our FMS may be good formulations to deliver the analgesics and suitable for the treatment of severe pain over long periods.

Analgesics, Opioid↗