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Smart hydrogels play an increasingly important role in biomedical applications, since materials that are both biocompatible and multi-stimuli-responsive are highly desirable. A simple, organic solvent-free method is presented to synthesize a biocompatible hydrogel that undergoes a sol-gel transition in response to multiple stimuli. Methoxy-poly(ethylene glycol) (mPEG) is modified into carboxylic-acid-terminated-methoxy-poly(ethylene glycol) (mPEG-acid), which is then grafted onto chitosan via amide linkages yielding mPEG- g-chitosan. Grafting of mPEG onto hydrophobic chitosan imparts hydrophilic properties to the resultant polymer. The mPEG- g-chitosan gel exhibits a controllable multi-stimuli-responsive property. The balance between hydrophilicity and hydrophobicity is believed to confer mPEG-g-chitosan with stimuli-responsive behavior. The effect of salt concentration, solute concentration, temperature, and pH on the sol-gel transition of mPEG- g-chitosan is evaluated and the underlying mechanisms of mPEG- g-chitosan polymer packing and gelation property is discussed. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 13C-, 29Si-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 nanoparticles with a stable polygonal geometry, consisting of ordered silane layers of 6nm 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]