• Journal of Pharmaceutical Investigation
• /
• 제40권4호
• /
• pp.201-212
• /
• 2010

Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

• Biotechnology and Bioprocess Engineering:BBE
• /
• 제11권3호
• /
• pp.262-267
• /
• 2006

The objective of this study was to develop new self-organized nanogels as a means of drug delivery in patients with cancer. Pullulan (PUL) and deoxycholic acid (DOCA) were conjugated through an ester linkage between the hydroxyl group in PUL and the carboxyl group in DOCA. Three types of PUL/DOCA conjugates were obtained, differing in the number of DOCA substitutions (DS; 5, 8, or 11) per 100 PUL anhydroglucose units. The physicochemical properties of the resulting nanogels were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of DS 11 was the smallest (approx. 100 nm), and the size distribution was unimodal. To determine the organizing behavior of these conjugates, we calculated their critical aggregation concentrations (CACs) in a 0.01-M phosphate buffered saline solution. They were $10.5{\times}10^{-4}mg/mL,\;7.2{\times}10^{-4} mg/mL,\;and\;5.6{\times}10^{-4} mg/mL$ for DS 5, 8, and 11, respectively. This indicates that DOCA can serve as a hydrophobic moiety to create self-organized nanogels. To monitor the drug-releasing behavior of these nanogels, we loaded doxorubicin (DOX) onto the conjugates. The DOX-loading efficiency increased with the degree of DOCA substitution. The release rates of DOX from PUL/DOCA nanogels varied inversely with the DS. We concluded that the PUL/DOCA nanogel has some potential for use as an anticancer drug carrier because of its low CAC and satisfactory drug-loading capacity.

• Journal of Microbiology and Biotechnology
• /
• 제16권9호
• /
• pp.1369-1376
• /
• 2006

Self-organized nanogels were prepared from pullulan/biotin conjugates (PU/Bio) for the development of an effective anticancer drug delivery system. The degree of biotin substitution was 11, 19, and 24 biotin groups per 100 anhydroglucose units of pullulan. The physicochemical properties of the nanogels (PU/Bio1, 2 and 3) in aqueous media were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of all the samples was less than 300 nm with a unimodal size distribution. The critical aggregation concentrations (CACs) of the nanoparticles in distilled water were $2.8{\times}10^{-2},\;1.6{\times}10^{-2}$, and $0.7{\times}10^{-2}mg/ml$ for the PU/Bio1, 2, and 3, respectively. The aggregation behavior of the nanogels indicated that biotin can perform as a hydrophobic moiety. To observe the specific interaction with a hepatic carcinoma cell line (HepG2), the conjugates were labeled with rhodamine B isothiocyanate (RITC) and their intensities measured using a fluorescence microplate reader. The HepG2 cells treated with the fluorescence-labeled PU/Bio nanoparticles were strongly luminated compared with the control (pullulan). Confocal laser microscopy also confirmed internalization of the PU/Bio nanogels into the cancer cells. Such results demonstrated that the biotin in the conjugate acted as both a hydrophobic moiety for self-assembly and a tumor-targeting moiety for specific interaction with tumor cells. Consequently, PU/Bio nanogels would appear to be a useful drug carrier for the treatment of liver cancer.