Search

Hydrophobically modified glycol chitosan (HGC) nanoparticles loaded with mono-lithocholic acid-conjugated exendin-4 at the Lys(27) residue (LAM1-Ex4) were prepared and characterized by particle size measurement, proteolytic stability, in vitro drug-release profile, and in vivo antidiabetic effects in a db/db diabetic mouse model. Compared with Ex-4-loaded HGC nanoparticles (Ex4/HGC NPs) prepared as a control, LAM1-Ex4-loaded HGC nanoparticles (LAM1-Ex4/HGC NPs) showed improved drug-loading efficiency, small particle size, enhanced resistance against proteolytic digestion, and an extended in vitro drug release profile. These findings may be attributable to the strong hydrophobic interaction between LAM1-Ex4 and the inner core of HGC. Furthermore, LAM1-Ex4/HGC NPs showed prolonged hypoglycemic efficacy in db/db mice, lasting 1 week after a single subcutaneous administration. The present study demonstrated that LAM1-Ex4/HGC NPs have considerable potential as a long-acting sustained-release antidiabetic system for type 2 diabetes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hydrophobically modified glycol chitosan (hGC) conjugates spontaneously form self-assembled nanoparticles (NPs) in aqueous conditions, and glycol chitosan NPs (CNPs) have been extensively studied for the past few decades. For disease-specific theranostics, CNPs could be simply modified with imaging agents, and the hydrophobic domains of hGC are available for encapsulation of various drugs. Based on the excellent physiochemical and biological properties, CNPs have been investigated for multimodal imaging and target specific drug delivery. In particular, a recent application of CNPs has shown great potential as an efficient theranostic system because the CNPs could be utilized for a disease-specific theranostic delivery system of different imaging agents and therapeutics, simultaneously. Furthermore, various therapeutic agents including chemo-drugs, nucleotides, peptides, and photodynamic chemicals could be simply encapsulated into the CNPs through hydrophobic or charge-charge interactions. Under in vivo conditions, the encapsulated imaging agents and therapeutic drugs have been successfully delivered to targeted diseases. In this article, the overall research progress on CNPs is reviewed from early works. The current challenges of CNPs to overcome in theranostics are also discussed, and continuous studies would provide more opportunities for early diagnosis of diseases and personalized medicine., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A natural based polymer, chitosan has received widespread attention in drug delivery systems due to its valuable physicochemical and biological characteristics. In particular, hydrophobic moiety-conjugated glycol chitosan can form amphiphilic self-assembled glycol chitosan nanoparticles (GCNPs) and simultaneously encapsulate hydrophobic drug molecules inside their hydrophobic core. This GCNP-based drug delivery systems exhibit excellent tumor-homing efficacy, attributed to the long blood circulation and the enhanced permeability and retention effect; this tumor-targeting drug delivery results in improved therapeutic efficiency. In this review, we describe the requisite properties of GCNPs for cancer therapy as well as imaging for diagnosis, such as their basic characteristics, in vitro delivery efficiency and in vivo tumor-targeting ability.

The extensive use of human growth hormone (hGH), emerging as protein therapeutics, has been limited by its instability in biological fluids and short biological half-life. In this study, thiolated glycol chitosan bearing α-cyclodextrin (TGC-CD), in situ cross-linked by poly(ethylene glycol)-diacrylate (PEG-DA), was synthesized to develop a sustained release system for PEGylated hGH (PEG-hGH). TGC-CD could form a stable inclusion complex with PEG-hGH by the physical interaction between the inner cavity of CD and PEG. Such a complex was readily cross-linked in the presence of PEG-DA via a Michael-type addition reaction. From the in vitro release experiments of PEG-hGH, it was confirmed that PEG-hGH was completely released from the complex for 12 h in PBS (pH 7.4), whereas the release rate of PEG-hGH was significantly reduced by the chemical cross-linking of the complex. PEG-hGH, released from the cross-linked complexes, maintained its structural integrity, which was demonstrated using circular dichroism spectroscopy. Overall, TGC-CD might be useful for sustained delivery of PEG-hGH.

To develop chitosan based efficient gene carriers, highly purified chitosan oligosaccharides (COSs) were chemically modified with deoxycholic acid (DOCA). Owing to the amphiphilic characters, the DOCA-conjugated COSs (COSDs) formed self-aggregated nanoparticles in aqueous milieu. The physicochemical characterization revealed that the particle size of the nanoparticles was in the range of 200 approximately 240 nm and the critical aggregation concentration (cacs) was 0.012 approximately 0.046 g/L, depending on the degree of substitution (DS). As efficient gene carriers, the COSD nanoparticles showed superior gene condensation and protection of condensed gene from endonuclease attack than unmodified COSs. Furthermore, COSDs showed great potential for gene carrier with the high level of gene transfection efficiencies, even in the presence of serum. Considered with the negligible cytotoxic effects, DOCA-modified chitosan oligosaccharides can be considered as potential candidates for efficient non-viral gene carriers.

The extensive use of human growth hormone (hGH), emerging as protein therapeutics, has been limited by its instability in biological fluids and short biological half-life. In this study, thiolated glycol chitosan bearing α-cyclodextrin (TGC-CD), in situ cross-linked by poly(ethylene glycol)-diacryIate (PEG-DA), was synthesized to develop a sustained release system for PEGylated hGH (PEG-hGH). TGC-CD could form a stable inclusion complex with PEG-hGH by the physical interaction between the inner cavity of CD and PEG. Such a complex was readily cross-linked in the presence of PEG-DA via a Michael-type addition reaction. From the in vitro release experiments of PEG-hGH, it was confirmed that PEG-hGH was completely released from the complex for 12 h in PBS (pH 7.4), whereas the release rate of PEG-hGH was significantly reduced by the chemical cross-linking of the complex. PEG-hGH, released from the cross-linked complexes, maintained its structural integrity, which was demonstrated using circular dichroism spectroscopy. Overall, TGC-CD might be useful for sustained delivery of PEG-hGH. [ABSTRACT FROM AUTHOR]