Browsing by Author "Hsiao, Meng-Hsuan"

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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.
A temperature-induced and shear-reversible assembly of latanoprost-loaded amphiphilic chitosan colloids: Characterization and in vivo glaucoma treatment
(2014-07-01)
Hsiao, Meng-Hsuan
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Chiou, Shih-Hwa
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Larsson, Mikael
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Hung, Kuo-Hsuan
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Wang, Yi-Ling
Hydrogels composed of assembled colloids is a material class that is currently receiving much interest and shows great promise for use in biomedical applications. This emerging material class presents unique properties derived from the combination of nanosized domains in the form of colloidal particles with a continuous gel network and an interspersed liquid phase. Here we developed an amphiphilic chitosan based, thermogelling, shear-reversible colloidal gel system for improved glaucoma treatment and addressed how preparation procedures and loading with the anti-glaucoma drug latanoprost and commonly used preservative benzalkonium chloride influenced the mechanical properties of and drug release from the colloidal gels. The results highlight that incorporated substances and preparation procedures have effects both on mechanical properties and drug release, but that the release of drug loaded in the colloidal carriers is mainly limited by transport out of the carriers, rather than by diffusion within the gel. The developed colloidal chitosan based gels hold outstanding biomedical potential, as confirmed by the ease of preparation and administration, low cytotoxicity in MTT assay, excellent biocompatibility and lowering of intraocular pressure for 40 days in a rabbit glaucoma model. The findings clearly justify further investigations towards clinical use in the treatment of glaucoma. Furthermore, the use of this shear-reversible colloidal gel could easily be extended to localized treatment of a number of critical conditions, from chronic disorders to cancer, potentially resulting in a number of new therapeutics with improved clinical performance. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Biomedical applications and colloidal properties of amphiphilically modified chitosan hybrids
(2013-09-01)
Larsson, Mikael
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Huang, Wei-Chen
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Hsiao, Meng-Hsuan
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Wang, Yen-Jen
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Nyden, Magnus
Chitosan is among the most abundant biopolymers on earth and has been either used or exhibited potential in a wide variety of industrial and biomedical applications. With the advancement of materials technologies, chitosan has been chemically modified to self-assemble into nanoarchitectures that are usable in advanced biomedical applications, such as drug nanocarriers, macroscopic injectables, tissue-engineering scaffolds, and nanoimaging agents. Colloidal amphiphilically modified chitosan (AMC) is a relatively recent material receiving increased attention with numerous publications addressing the medical advantages of specific systems. To date, many reviews have focused on the synthesis and biomedical properties of chitosan-based biomaterials, but a comprehensive study focusing on the colloidal properties of AMC in relation to biomedical performance appears to be lacking. This review provides a survey of the field, critically reviewing the colloidal properties and biomedical performance of AMC systems, such as nanoparticle drug delivery systems and macroscopic medical devices. Finally, the future development, market potential, and clinical implications of these promising colloidal-structured biomaterials are summarised. (C) 2013 Elsevier Ltd. All rights reserved.
Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide
(2012-08-10)
Hsiao, Meng-Hsuan
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Larsson, Mikael
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Larsson, Anette
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Evenbratt, Hanne
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Chen, Ying-Yu
Thermo-gelling injectable nanogels, with no burst release of loaded drug, were prepared by a simple route by combining self assembled nanocapsules of amphiphilically modified chitosan with glycerophosphate di-sodium salt and glycerol. The potential as a depot drug delivery system was demonstrated in vivo through the therapeutic effect of ethosuximide (ESM) loaded nanogels, suppressing spike wave discharges (SWDs) in Long Evan rat model. Simultaneously clearance of gels from the site of administration was monitored non-invasively using MRI. The gel structure was characterized using TEM and SEM, confirming the gels to be an assembly of nanocapsules and using two-photon microscopy to visualize the network structure. In vitro drug release studies using ESM revealed that the nanogels exhibited extended, mostly Fickian release. Finally, all investigated formulations displayed excellent cytotoxicity data determined by MTT assay using human retinal pigmented epithelium cells. All presented properties are highly desirable for injectable depot gels for drug delivery. (c) 2012 Elsevier B.V. All rights reserved.
Hexanoyl-Chitosan-PEG Copolymer Coated Iron Oxide Nanoparticles for Hydrophobic Drug Delivery
(2015-04-01)
Hsiao, Meng-Hsuan
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Mu, Qingxin
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Stephen, Zachary R.
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Fang, Chen
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Zhang, Miqin
Nanoparticle (NP) formulations may be used to improve in vivo efficacy of hydrophobic drugs by circumventing solubility issues and providing targeted delivery. In this study, we developed a hexanoyl-chitosan-PEG (CP6C) copolymer coated, paclitaxel (PTX)-loaded, and chlorotoxin (CTX) conjugated iron oxide NP (CTX-PTX-NP) for targeted delivery of PTX to human glioblastoma (GBM) cells. We modified chitosan with polyethylene glycol (PEG) and hexanoyl groups to obtain the amphiphilic CP6C. The resultant copolymer was then coated onto oleic acid-stabilized iron oxide NPs (OA-IONP) via hydrophobic interactions. PTX, a model hydrophobic drug, was loaded into the hydrophobic region of IONPs. CTX-PTX-NP showed high drug loading efficiency (>30%), slow drug release in PBS and the CTX-conjugated NP was shown to successfully target GBM cells. Importantly, the NPs showed great therapeutic efficacy when evaluated in GBM cell line U-118 MG. Our results indicate that this nanoparticle platform could be used for loading and targeted delivery of hydrophobic drugs.
Highly electrostatically-induced detection selectivity and sensitivity for a colloidal biosensor made of chitosan nanoparticle decorated with a few bare-surfaced gold nanorods
(2014-02-15)
Jean, Ren-Der
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Cheng, Wei-Da
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Hsiao, Meng-Hsuan
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Chou, Fu-Hsuan
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Bow, Jong-Shing
Metallic nanoparticles have been utilized as an analytical tool to detecting a wide variety of organic analytes. Among them, gold nanoparticles demonstrating outstanding surface plasmonic resonance property have been well recognized and received wide attention for plasmon-based sensing applications. However, in literature, gold-based nanosensor has to be integrated with specific "ligand" molecule in order to gain molecular recognition ability. However, "ligand" molecules, included proteins, peptides, nucleic acids, etc. are expensive and vulnerable to environmental change, in the meantime, anchoring procedure of the "ligand" molecules to gold surface may be cost-ineffective and endangered to the ligand's activity, making a final analytic probe less reliable and risk in production capability. Here, we develop a new approach by designing a colloid-type sensor using a few "bare" Au nanorods deposited on the surface of a colloidal chitosan carrier. By tuning the solution pH, the resulting colloidal nanoprobe is capable of detecting proteins, i.e., human serum albumin and lysozyme, with high specificity and sensitivity. This new approach allows a new type of the molecular probes to be well manipulated to monitor important biomolecules for medical detection, diagnosis, and bioengineering applications. (C) 2013 Elsevier B.V. All rights reserved.
Improved pH-responsive amphiphilic carboxymethyl-hexanoyl chitosan-poly(acrylic acid) macromolecules for biomedical applications
(2013)
Hsiao, Meng-Hsuan
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Lin, Kuan-Hui
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Liu, Dean-Mo
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材料科學與工程學系
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Department of Materials Science and Engineering
In this communication, we report a new type of amphiphilic carboxymethyl-hexanoyl chitosan (CHC)-poly(acrylic acid) (PAA) hybrid macromolecule, which was successfully prepared through polymerization of acrylic acid (AA) in the presence of amphiphilic CHC. The chemical structure of the hybrid was characterized by FT-IR and H-1 NMR, which confirmed a chemical linkage between the amine groups of CHC and hydroxyl groups of AA. This CHC-PAA hybrid exhibited amphiphilic property as the original CHC rendering the self-assembling capability to be tunable in terms of AA concentration. Compared with the existing pristine chitosan-PAA co-polymers, this CHC-PAA hybrid exhibited a relatively high pH-responsive volumetric change by 10-100 times compared with the existing alternatives reported in the literature. The hybrid nanoparticles showed excellent encapsulation efficiency greater than 90% for a hydrophobic anti-cancer substance, (S)-(+)-camptothecin. A pH-responsive drug release behavior was systematically evaluated. Besides, this hybrid also revealed excellent cytocompatibility towards the MCF-7 and BCE cell lines, which, associated with its structural stability, suggests this new type of CHC-PAA hybrid to be a promising biomaterial for oral drug delivery application.
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.
Nano-hybrid carboxymethyl-hexanoyl chitosan modified with (3-aminopropyl)triethoxysilane for camptothecin delivery
(2012-06-20)
Hsiao, Meng-Hsuan
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Tung, Tsan-Hua
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Hsiao, Chi-Sheng
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Liu, Dean-Mo
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材料科學與工程學系
Silane-modified amphiphilic chitosan was synthesized by anchoring a silane coupling agent, (3-aminopropyl)triethoxysilane, to a novel amphiphilic carboxymethyl-hexanoyl chitosan (CHC). The chemical structure of this new organic-inorganic hybrid molecule was characterized by FTIR and C-13-, Si-29-nuclear magnetic resonance, while the structural evolution was examined using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS). Experimental results indicated a self-assembly behaviour of molecules into nanopartides with a stable polygonal geometry, consisting of ordered silane layers of 6 nm in thickness. The self-assembly property was found to be influenced by chemical composition and concentration of silane incorporated, while the size can be varied by the amount of anchored silane. It was also demonstrated that such vesicle exhibited excellent cytocompatibility and cellular internalization capability in ARPE-19 cell line, and presented well-controlled encapsulation and release profiles for (S)-(+)-camptothecin. These unique properties render it as a potential drug delivery nanosystem. (C) 2012 Elsevier Ltd. All rights reserved.
Stable and Efficient Paclitaxel Nanoparticles for Targeted Glioblastoma Therapy
(2015-06-03)
Mu, Qingxin
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Jeon, Mike
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Hsiao, Meng-Hsuan
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Patton, Victoria K.
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Wang, Kui
Development of efficient nanoparticles (NPs) for cancer therapy remains a challenge. NPs are required to have high stability, uniform size, sufficient drug loading, targeting capability, and ability to overcome drug resistance. In this study, the development of a NP formulation that can meet all these challenging requirements for targeted glioblastoma multiform (GBM) therapy is reported. This multifunctional NP is composed of a polyethylene glycol-coated magnetic iron oxide NP conjugated with cyclodextrin and chlorotoxin (CTX) and loaded with fluorescein and paclitaxel (PTX) (IONP-PTX-CTX-FL). The physicochemical properties of the IONP-PTX-CTX-FL are characterized by transmission electron microscope, dynamic light scattering, and high-performance liquid chromatography. The cellular uptake of NPs is studied using flow cytometry and confocal microscopy. Cell viability and apoptosis are assessed with the Alamar Blue viability assay and flow cytometry, respectively. The IONP-PTX-CTX-FL had a uniform size of approximate to 44 nm and high stability in cell culture medium. Importantly, the presence of CTX on NPs enhanced the uptake of the NPs by GBM cells and improved the efficacy of PTX in killing both GBM and GBM drug-resistant cells. The IONP-PTX-CTX-FL demonstrated its great potential for brain cancer therapy and may also be used to deliver PTX to treat other cancers.