Browsing by Author "Chou, Hao-Syun"

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A pH-responsive amphiphilic chitosan-pyranine core-shell nanoparticle for controlled drug delivery, imaging and intracellular pH measurement
(2014)
Chou, Hao-Syun
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Hsiao, Meng-Hsuan
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Hung, Wei-Yang
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Yen, Tin-Yo
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Lin, Hui-Yi
A pH-responsive multifunctional core-shell nanoparticle, named CHC-PY nanoparticle, was successfully synthesized through electrostatic interaction of a thin shell of fluorescent pyranine dye (PY) with amphiphilic carboxymethylhexanoyl chitosan (CHC) nanoparticles. Upon encapsulating an anticancer drug, camptothecin (CPT), the CHC-PY nanoparticles exhibited an excellent drug loading efficiency (>95%). The resulting CPT-loaded CHC-PY nanoparticles also exhibited efficient cell internalization and good pH-responsive behavior. After being internalized (via efficient endocytosis pathway), the presence of fluorescent PY shell showed a pH-dependent emission characteristic which allowed the internalized CHC-PY nanoparticles acting as an indicator to distinguish the acidic microenvironment of cancerous cells, compared with normal cells. The pH-sensitive PY shell also acted as a modulator to control the CPT release wherein a higher release rate was detected at lower pH value, which is essentially a potential therapeutic niche for anticancer purposes. This new type of CHC-PY core-shell nanoparticle provides multiple functionality, where a synergistic performance of nanotherapeutics, imaging and even diagnosis at a cellular resolution can be achieved simultaneously.
Inhibition of Periodontitis Induction Using a Stimuli-Responsive Hydrogel Carrying Naringin
(2017-02-01)
Chang, Po-Chun
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Chao, Yi-Chi
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Hsiao, Meng-Hsuan
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Chou, Hao-Syun
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Jheng, Yi-Han
Background: Developing a drug carrier with favorable handling characteristics that can respond to environmental changes after inflammation, such as pH changes, may be beneficial for treating periodontitis. This study aims to investigate the preclinical feasibility of using naringin, a naturally derived polymethoxylated flavonoid compound with anti-inflammatory properties, to inhibit periodontitis induction via a thermogelling and pH-responsive injectable hydrogel. Methods: The hydrogel was made of amphipathic carboxy-methyl-hexanoyl chitosan (CHC), beta-glycerol phosphate (beta-GP), and glycerol. Thermogelling and pH-responsive characteristics of the hydrogel, as well as cell viability after treatment with the hydrogel containing naringin, were evaluated in vitro. Hydrogel was subgingivally delivered when experimental periodontitis was induced in vivo, and therapeutic effect was evaluated with microcomputed tomography imaging, histology, and expression of inflammation-associated genes, including toll-like receptor (TLR) 2, the receptor for advanced glycation end products (RAGE), myeloid differentiation primary response gene-88, and tumor necrosis factor (TNF)-alpha. Results: The hydrogel was consistently fluidic at 4 degrees C but rapidly gelled at 37 degrees C. Release of naringin was faster at pH 5.5 to 6.5, and viability was significantly promoted by treatment with 0.85% naringin. Naringin-carrying CHC-beta-GP-glycerol hydrogel sites showed significantly reduced periodontal bone loss (P < 0.05) and inflammatory infiltration (P < 0.01) as well as significantly downregulated TLR2 (P < 0.05), RAGE (P < 0.01), and TNF-alpha (P < 0.05) relative to the sites with experimental periodontitis alone. Conclusion: Naringin-carrying CHC-beta-GP-glycerol colloidal hydrogel can be used to inhibit induction of experimental periodontitis with favorable handling and inflammation-responsive characteristics.
Injectable insulin-lysozyme-loaded nanogels with enzymatically-controlled degradation and release for basal insulin treatment: In vitro characterization and in vivo observation
(2016-02-28)
Chou, Hao-Syun
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Larsson, Mikael
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Hsiao, Meng-Hsuan
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Chen, Yi-Chieh
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Roeding, Magnus
Diabetes is a common global disease that causes immense suffering for individuals and huge costs for the health care system. To minimize complications such as organ degeneration, diabetic patients are required to undergo treatments to maintain the blood glucose level in the normal range, ideally mimicking normal insulin secretion. The normal physiological insulin secretion pattern in healthy individuals consists of a base (basal) level through the day and increased secretion after meals (bolus insulin). Thus effective treatments may combine long acting, low-level insulin therapy with boosts of short acting insulin and/or oral agents. To achieve long term management of basal insulin level, an injectable insulin-loaded gel composed of self-assembled nanoparticles from carboxymethyl-hexanoyl chitosan (CHC) and integrated lysozyme for controlled biodegradation and insulin release was developed. In vitro characterizations and evaluations confirmed that lysozyme was active on CHC and that the amount of lysozyme in a CHC hydrogel determined the degradation and insulin release rate. The degradation products were found to be highly cytocompatible using a cell assay. In vivo evaluation of the system in a diabetic mouse model revealed that the fasted blood glucose level could be maintained in the normal range for 10 days with a single injection of insulin-loaded CHC-lysozyme gel. The insulin-loaded CHC-lysozyme gels clearly show promise for use as a novel injectable long-acting insulin delivery system, with potential to manage the basal insulin level for many days with a single injection. (C) 2015 Elsevier B.V. All rights reserved.