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Biomedical subjects

Hasoo Seong

Publications and source records attributed to Hasoo Seong.

5 recordsLinked to original sources

In vivo distribution and antitumor activity of heparin-stabilized doxorubicin-loaded liposomes.

The purpose of this study was to investigate the effect of heparin conjugation to the surface of doxorubicin (DOX)-loaded liposomes on the circulation time, biodistribution and antitumor activity after intravenous injection in murine B16F10 melanoma tumor-bearing mice. The heparin-conjugated liposomes (heparin-liposomes) were prepared by fixation of the negatively charged heparin to the positively charged liposomes. The existence of heparin on the liposomal surface was confirmed by measuring the changes in the particle size, zeta potential and heparin amount of the liposomes. The stability of the heparin-liposomes in serum was higher than that of the control liposomes, due to the heparin-liposomes being better protected from the adsorption of serum proteins. The DOX-loaded heparin-liposomes showed high drug levels for up to 64 h after the intravenous injection and the half-life of DOX was approximately 8.4- or 1.5-fold higher than that of the control liposomes or polyethyleneglycol-fixed liposomes (PEG-liposomes), respectively. The heparin-liposomes accumulated to a greater extent in the tumor than the control or PEG-liposomes as a result of their lower uptake by the reticuloendothelial system cells in the liver and spleen. In addition, the DOX-loaded heparin-liposomes retarded the growth of the tumor effectively compared with the control or PEG-liposomes. These results indicate the promising potential of heparin-liposomes as a new sterically stabilized liposomal delivery system for the enhancement of the therapeutic efficacy of chemotherapeutic agents.

Animals↗

Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes.

Temperature-sensitive liposomes (TS-liposomes) have been studied for chemotherapeutic purposes to enhance the release of anticancer drugs at tumor sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS-liposomes). PETS-liposomes significantly increased in vitro drug release in serum compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore, incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the stabilities of liposomes in serum by inhibiting protein adsorption. In addition, to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS-liposomes, the in vivo antitumor activity of liposomes in combination with hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS-liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS-liposomes was enhanced significantly when they were administered in combination with hyperthermia. PETS-liposomes were found to be highly efficacious carriers for the in vivo delivery of anticancer drugs, and to have potential anticancer applications in combination with hyperthermia.

Acrylic Resins↗

BCNU-loaded poly(D, L-lactide-co-glycolide) wafer and antitumor activity against XF-498 human CNS tumor cells in vitro.

Implantable polymeric device that can release chemotherapeutic agent directly into central nervous system (CNS) has had an impact on malignant glioma therapy. The purpose of our study was to develop an implantable polymeric device, which can release intact 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for long-term period over 1 month, and to evaluate its cytotoxicity against XF 498 human CNS tumor cells in vitro. BCNU was incorporated into biodegradable poly(D,L-lactide-co-glycolide) (PLGA), by using spray-drying method. BCNU-loaded PLGA microparticles were characterized by scanning electron microscopy (SEM), powder X-ray diffraction, and differential scanning calorimetry. SEM observation of the microparticles showed that the microparticles were spherical, i.e. microspheres. Homogeneous distribution of BCNU in PLGA microsphere was confirmed by significant reduction of crystallinity of BCNU. Microspheres were fabricated into wafers with flat and smooth surface by direct compression method. In vitro release of BCNU in pH 7.4 phosphate buffered saline was prolonged up to 8 weeks after short initial burst period. Antitumor activity of BCNU-loaded PLGA wafer against XF 498 human CNS tumor cells continued over 1 month and, PLGA only did not affect the growth of the cells. Meanwhile, the cytotoxic activity of BCNU powder disappeared within 12 h. These results strongly suggest that the BCNU/PLGA formulations increase release period of carmustine in vivo and also be useful in the development of implantable polymeric device for malignant glioma.

Antineoplastic Agents, Alkylating↗

Preparation of liposomes with glucose binding sites: liposomes containing di-branched amino acid derivatives.

Di-branched amino acid derivatives, such as dihexadecyl-glutamate-glutamine (DHD-glu-gln), dihexadecyl-glutamate-asparagine (DHD-glu-asn) and dihexadecyl-glutamate-glutamic acid (DHD-glu-glu), were synthesized, and then incorporated into lipid vesicles (liposomes) using dipalmitoylphosphatidylcholine (DPPC). To form binding sites toward glucose, the liposomes containing amino acid derivatives were mixed with glucose above the phase transition temperature (PTT) of DPPC and subsequently the temperature was lowered below the PTT. The glucose-binding affinity of liposomes containing amino acid derivative with or without glucose imprinting was evaluated by surface plasmon resonance (SPR) and equilibrium dialysis technique. SPR of liposomes containing each amino acid derivative or three amino acid derivatives revealed that only the liposomes containing all three amino acid derivatives had glucose-binding affinity and that the glucose-imprinting process was essential to fix the amino acid derivatives into a glucose binding site on the liposomes. Equilibrium dialysis studies of glucose-imprinted liposomes produced curvilinear Scatchard plots, indicating that the amino acid derivatives play a role in glucose binding. Di-branched amino acid derivatives synthesized in this study are promising agent for the development of biocompatible synthetic glucose binding materials.

1,2-Dipalmitoylphosphatidylcholine↗

Glucose binding to molecularly imprinted polymers.

The main goal of this study was to prepare molecularly imprinted polymers (MIPs) with glucose recognition sites and to evaluate their glucose-binding properties for potential applications in glucose sensing and self-regulating insulin delivery devices. To mimic glucose-binding sites of natural proteins, monomers possessing functional groups similar to amino acids were used. Vinyl acetic acid (VAA), acrylamide (AAm), 4-pentenoic acid (PA), and allyl benzene (AB) were copolymerized with a cross-linking agent (N,N'-methylenebisacrylamide, BIS) in the presence of glucose as a template. The binding affinity of glucose to MIPs was examined by using an equilibrium dialysis technique. The dissociation constants of the MIPs were determined by Scatchard analysis. MIPs showed glucose-binding affinity, while polymers synthesized in the absence of glucose template did not show a glucose-binding property. MIPs composed of VAA, AAm, PA, and AB at optimized mole ratios of monomers and cross-linker showed the highest glucose-binding affinity, KD = 1.66 mM, which is comparable to that of a well-known glucose binding protein, concanavalin A (KD = 1.84 mM). The affinity between monomer and glucose was in the order VAA > AAm > AB > PA.

Binding Sites↗