• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1725-1728
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• 2015

Objective: To explore effects of paclitaxel-loaded poly lactic-co-glycolic acid (PLGA) particles on the viability of human hepatocellular carcinoma (HCC) HepG2 cells. Materials and Methods: The viability of HepG2 cells was assessed using MTT under different concentrations of prepared paclitaxel-loaded particles and paclitaxel (6.25, 12.5, 25, 50, and 100 mg/L), and apoptosis was analyzed using Hochest33342/Annexin V-FITC/PI combined with an IN Cell Analyzer 2000. Results: Paxlitaxel-loaded nanoparticles were characterized by narrow particle size distribution (158.6 nm average particle size). The survival rate of HepG2 cells exposed to paclitaxel-loaded PLGA particles decreased with the increase of concentration and time period (P<0.01 or P<0.05), the dose- and time-dependence indicating sustained release (P<0.05). Moreover, apoptosis of HepG2 cells was induced, again with an obvious dose- and time-effect relationship (P<0.05). Conclusions: Paclitaxel-loaded PLGA particles can inhibit the proliferation and induce the apoptosis of HCC HepG2 cells. This new-type of paclitaxel carrier body is easily made and has low cost, good nanoparticle characterization and sustained release. Hence, paclitaxel-loaded PLGA particles deserve to be widely popularized in the clinic.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2335-2340
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• 2014

Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physicochemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmedpolymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at $38^{\circ}C$ over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

• BMB Reports
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• v.40 no.5
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• pp.731-739
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• 2007

The purpose of this study was to develop paclitaxel-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles coated with cationic SM5-1 single-chain antibody (scFv) containing a polylysine (SMFv-polylys). SM5-1 scFv (SMFv) is derived from SM5-1 monoclonal antibody, which binds to a 230 kDa membrane protein specifically expressed on melanoma, hepatocellular carcinoma and breast cancer cells. SMFv-polylys was expressed in Escherichia coli and purified by cation-exchange chromatography. Purified SMFv-polylys was fixed to paclitaxel-loaded PLGA nanoparticles to form paclitaxel-loaded PLGA nanoparticles coated with SMFv-polylys (Ptx-NP-S). Ptx-NP-S was shown to retain the specific antigen-binding affinity of SMFv-polylys to SM5-1 binding protein-positive Ch-hep-3 cells. Finally, the cytotoxicity of Ptx-NP-S was evaluated by a non-radioactive cell proliferation assay. It was demonstrated that Ptx-NP-S had significantly enhanced in vitro cytotoxicity against Ch-hep-3 cells as compared with non-targeted paclitaxel-loaded PLGA nanoparticles. In conclusion, our results suggest that cationic SMFv-polylys has been successfully generated and may be used as targeted ligand for preparing cancer-targeted nanoparticles.

• Macromolecular Research
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• v.15 no.6
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• pp.513-519
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• 2007

Self-assembled nanoparticles have great potential to act as vehicles for hydrophobic drug delivery. Understanding nanoparticle cellular internalization is essential for designing drugs intended for intracellular delivery. Here, the endocytosis and exocytosis of fluorescein isothiocyanate (FITC)-conjugated glycol chitosan (FGC) self-assembled nanoparticles were investigated by flow cytometry and confocal microscopy. The cellular internalization of FGC nanoparticles was initiated by nonspecific interactions between nanoparticles and cell membranes. Although adsorptive endocytosis of the nanoparticles occurred quickly, significant amounts of FGC nanoparticles were exocytosed, particularly in the early stage of endocytosis. The amount of exocytosed nanoparticles was dependent on the pre-incubation time with nanoparticles, suggesting that exocytosis is dependent on the progress of endocytosis. FGC nanoparticles internalized by adsorptive endocytosis were distributed in the cytoplasm, but not in the nucleus. In vitro cell cycle analysis demonstrated that FGC nanoparticles delivered paclitaxel into the cytoplasm and were effective in arresting cancer cell growth.

• Bulletin of the Korean Chemical Society
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• v.30 no.5
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• pp.1085-1087
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• 2009

Bare metal stents which were used to treat coronary artery disease have several biochemical problems. Polymerbased drug-eluting stents (DES) have opened up a new paradigm in the treatment of in-stent restenosis. Many studies and research programmes have proved that DES can prevent restenosis. In our study, paclitaxel-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles have been deposited along the three dimensional scaffold of coronary stents by a method using self-assembling properties of colloidal particles. We found that the nanoparticles were deposited uniformly and closely packed. The amount of paclitaxel was easily controlled by the drug content of the nanoparticles and the deposition count.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.381-386
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• 2011

Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

• Journal of Pharmaceutical Investigation
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• v.38 no.2
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• pp.127-134
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• 2008

Peroral administration is the most convenient one for the administration of pharmaceutically active compounds. Most of poorly water-soluble drugs administered via the oral route, however, remain poorly available due to their precipitation in the gastrointestinal (GI) tract and low permeability through intestinal mucosa. In this study, one of drug delivery carriers, lipid nanoparticles (LNPs) were designed in order to reduce side effects and improve solubility and stability in GI tract of the poorly water soluble drugs. However, plain LNPs are generally unstable in the GI tract and susceptible to the action of acids, bile salts and enzymes. Accordingly, the surface of LNPs was modified with polyethylene glycol (PEG) for the purpose of improving solubility and GI stability of paclitaxel (PTX) in vitro. PEG-modified LNPs containing PTX was prepared by spontaneous emulsification and solvent evaporation (SESE) method and characterized for mean particle diameter, entrapping efficiency, zeta potential value and in vitro GI stability. Mean particle diameter and zeta potential value of PEG-modified LNP containing PTX showed approximately 86.9 nm and -22.9 mV, respectively. PTX entrapping efficiency was about 70.5% determined by UV/VIS spectrophotometer. Futhermore, change of particle diameter of PTX-loaded PEG-LNPs in simulated GI fluids and bile fluid was evaluated as a criteria of GI stability. Particle diameter of PTX-loaded PEG-LNPs were preserved under 200 nm for 6 hrs in simulated GI fluids and bile fluid at $37^{\circ}C$ when DSPE-mPEG2000 was added to formulation of LNPs above 4 mole ratio. As a result, PEG-modified LNPs improved stability of plain LNPs that would aggregate in simulated GI fluids and bile solution. These results indicate that LNPs modified with biocompatible and nontoxic polymer such as PEG might be useful for enhancement of GI stability of poorly water-soluble drugs and they might affect PTX absorption affirmatively in gastrointestinal mucosa.

• Bulletin of the Korean Chemical Society
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• v.34 no.6
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• pp.1800-1808
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• 2013

Dual-responsive amphiphilic block copolymers were synthesized by combining enzymatic ring-opening polymerization (eROP) of ${\varepsilon}$-caprolactone (CL) and ATRP of N,N-dimethylamino-2-ethyl methacrylate (DMAEMA). The obtained block copolymers were characterized by gel permeation chromatography (GPC), $^1H$ NMR and FTIR-IR. The critical micelle concentration (CMC) of copolymer was determined by fluorescence spectra, it can be found that with hydrophilic block (PDMAEMA) increasing, CMC value of the polymer sample increased accordingly, and the CMC value was 0.012 mg/mL, 0.025 mg/mL and 0.037 mg/mL for $PCL_{50}$-b-$PDMAEMA_{68}$, $PCL_{50}$-b-$PDMAEMA_{89}$, $PCL_{50}$-b-$PDMAEMA_{112}$, $PCL_{50}$-b-$PDMAEMA_{89}$ was chosen as drug carrier to study in vitro release profile of anti-cancer drug (taxol). The temperature and pH dependence of the values of hydrodynamic diameter (Dh) of micelles, and self-assembly of the resulting block copolymers in water were evaluated by dynamic light scattering (DLS). The result showed that with the temperature increasing and pH decreasing, the Dh decreased. Drug-loaded nanoparticles were fabricated using paclitaxel as model. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) had been explored to study the morphology of the hollow micelles and the nanoparticles, revealing well-dispersed spheres with the average diameters both around 80 nm. In vitro release kinetics of paclitaxel from the nanoparticles was also investigated in different conditions (pH and temperature, etc.), revealing that the drug release was triggered by temperature changes upon the lower critical solution temperature (LCST) at pH 7.4, and at $37^{\circ}C$ by an increase of pH.

• Polymer(Korea)
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• v.35 no.2
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• pp.119-123
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• 2011

To develop hyaluronic acid (HA)-based anticancer agent carrier, hyaluronic acid was chemically modified with the hydrophobic group of deoxycholic acid(DA). The physicochemical properties of the deoxycholic acid-conjugated HA (HADA) were investigated by using $^1H$ NMR, FTIR spectrophotometer and TEM. Paclitaxel (Tx)-loaded HADA nanoparticles were prepared by a dialysis method. The loading efficiency of drug and drug contents of Tx-loaded HADA nanoparticles (HADA-Tx) were measured by HPLC. The anticancer activity of HADA-Tx was investigated by its cytotoxicity against KB cell in vitro. The HADA-Tx was shown to have the superior potential for the anticancer drug delivery.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9249-9258
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• 2014

Background: The encapsulation of curcumin (Cur) in polylactic-co-glycolic acid (PLGA) nanoparticles (Cur-NPs) was designed to improve its solubility and stability. Conjugation of the Cur-NPs with anti-P-glycoprotein (P-gp) antibody (Cur-NPs-APgp) may increase their targeting to P-gp, which is highly expressed in multidrugresistance (MDR) cancer cells. This study determined whether Cur-NPs-APgp could overcome MDR in a human cervical cancer model (KB-V1 cells) in vitro and in vivo. Materials and Methods: First, we determined the MDR-reversing property of Cur in P-gp-overexpressing KB-V1 cells in vitro and in vivo. Cur-NPs and Cur-NPs-APgp, in the range 150-180 nm, were constructed and subjected to an in vivo pharmacokinetic study compared with Cur. The in vitro and in vivo MDR-reversing properties of Cur-NPs and Cur-NPs-APgp were then investigated. Moreover, the stability of the NPs was determined in various solutions. Results: The combined treatment of paclitaxel (PTX) with Cur dramatically decreased cell viability and tumor growth compared to PTX treatment alone. After intravenous injection, Cur-NPs-APgp and Cur-NPs could be detected in the serum up to 60 and 120 min later, respectively, whereas Cur was not detected after 30 min. Pretreatment with Cur-NPs-APgp, but not with NPs or Cur-NPs, could enhance PTX sensitivity both in vitro and in vivo. The constructed NPs remained a consistent size, proving their stability in various solutions. Conclusions: Our functional Cur-NPs-APgp may be a suitable candidate for application in a drug delivery system for overcoming drug resistance. The further development of Cur-NPs-APgp may be beneficial to cancer patients by leading to its use as either as a MDR modulator or as an anticancer drug.