Mitsuko Takenaga - Academia.edu (original) (raw)

Papers by Mitsuko Takenaga

Journal of St. Marianna University, 2016

Regenerative Medicine, Jul 1, 2012

Cell Transplantation, Aug 1, 2008

Biochemical and Biophysical Research Communications, Jul 1, 2004

Drug Delivery, 2006

To show the possibility of sustained-release insulin formulation composed of PLGA, the optimum on... more To show the possibility of sustained-release insulin formulation composed of PLGA, the optimum one was administered to BioBreeding rat, a model of spontaneous type I diabetes mellitus (IDDM). Every 2 weeks subcutaneous administration made their blood glucose level depend on the insulin release and food intake. However, all of them kept alive with little change or rather a little gain in body weight. Furthermore, some of pregnant rats with intermittent treatment bore fetuses, although additional insulin therapy seemed necessary. Therefore, the formulation could become a new tool as a provider of basal insulin for IDDM patients.

International Journal of Pharmaceutics, Mar 1, 2004

Journal of Controlled Release, 2008

European Respiratory Journal, Sep 1, 2011

Many studies demonstrating lung repair by means of stem/progenitor cells or growth factors have b... more Many studies demonstrating lung repair by means of stem/progenitor cells or growth factors have been reported in animal emphysema models. We focused on adipose tissue-derived stromal/stem cells (ASCs) for regenerative medicine, since it has a high potential to secrete multiple angiogenic factors and differentiate various kinds of cells. To demonstrate the therapeutic impact of ASCs transplantation and to elucidate mechanisms of the effects in rat emphysema models. ASCs were isolated from Wistar rat inguinal subcutaneous adipose tissue. Emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE). One week after induction of PPE, cell transplantation was performed intravenously. At 1 and 2 weeks after transplantation, we assessed arterial blood analysis and histopathological changes and measurement of chemokine levels. After PPE induction, arterial oxygen pressure (PaO 2 ) was reduced. After ASCs transplantation, PaO 2 significantly improved. In addition, transplantation significantly prevented the enlargement of alveolar airspace elicited by PPE. PPE gradually reduced the levels of endogenous hepatocyte growth factor (HGF) in lung tissue. ASCs augmented HGF level was significantly higher than PPE alone. ASCs from GFP transgenic rats were localized at damaged alveolar spaces. Immunohistochemical analysis revealed some grafted ASCs were expressed CD31 or SP-C at 1w after transplantation. The results showed that transplantation of ASCs for emphysema rats improved gas exchange and inhibit enlargement of the airspaces. Transplantation of ASCs may be new therapeutic strategy to improve pulmonary function and inhibit alveolar destruction in COPD.

Journal of Controlled Release, Feb 1, 2005

We synthesized lecithinized brain-derived neurotrophic factor (lecithinized-BDNF), in which an av... more We synthesized lecithinized brain-derived neurotrophic factor (lecithinized-BDNF), in which an average of three molecules of a lecithin derivative were bound to recombinant human BDNF. We evaluated its pharmacological activity in C57BL/KsJ-db/db mice, and assessed its targetability and affinity for the nervous system. Subcutaneously administered lecithinized-BDNF markedly reduced the plasma glucose level, food intake, and body weight in C57BL/KsJ-db/db diabetic mice. Its potency was more than 20 times greater than that of unmodified BDNF. We then studied the mechanism for the markedly enhanced pharmacological activity. In vitro cell growth activity of lecithinized-BDNF using the MTT assay was lower than unmodified BDNF, probably due to steric hindrance of the lecithin moieties. While the plasma BDNF level after subcutaneous administration of lecithinized-BDNF was not higher compared with unmodified BDNF. However, higher amount of lecithinized-BDNF accumulated in the spinal cord was observed. Lastly, we found that in vitro binding capacity of lecithinized-BDNF for PC-pAB1 neural cells was much higher than unmodified BDNF. Moreover, lecithinized-BDNF bound to PC-pAB1 cells did not exchange with an excessive amount of unmodified BDNF or an excess of lecithinized-BDNF. PC-pAB1 cells treated with lecithinized-BDNF showed sustained mitogen-activated protein kinase (MAPK, ERK1/2) activation. These data would indicate that the high affinity of lecithinized-BDNF for the target cells, followed by prolonged MAPK activation, would play an important role in its potent pharmacological activity.

The Nippon journal of angio-cardiology, 1987

Journal of Controlled Release, May 1, 2005

We show a novel drug delivery system (DDS) for improved all-trans retinoic acid (atRA) therapy fo... more We show a novel drug delivery system (DDS) for improved all-trans retinoic acid (atRA) therapy for external treatments of photo-damaged skin. We prepared inorganic-coated atRA nanoparticles, in turn an egg-like structure in nano-scale (Nano-atRA), using boundary-organized reaction droplets. The interfacial properties of organic architectures, in atRA micelles, were used to template the nucleation of inorganic minerals. As a result, irritation and inflammation associated with atRA therapy were substantially reduced due to the complete encapsulation of the carboxylic function. Both irritative symptoms and physicochemical instability of the atRA micelle were improved. Since Nano-atRA which is prepared following to this new DDS system developmentally improved the permeability to the stratum corneum, the remarkable pharmacological effects were resulted in comparison with atRA as such as follows: (1) thicker epidermis than classical atRA treatment and (2) the overexpression of mRNA for heparin-binding epidermal growth factor (HB-EGF) as the provocation epidermal hyperplasia. Furthermore, we found a surprising boost in production of hyaluronan (HA) among the intercellular spaces of the basal and spinous cell layers in epidermis. Nano-atRA technology for atRA therapy could not only efficiently regulate keratinocyte cell proliferation and differentiation, but also markedly produce the additional benefit. Severely injured human skin by chronic ultraviolet irradiation will completely repair due to the accelerated turnover of skin tissue, which is induced by Nano-atRA.

Biochemical and Biophysical Research Communications, 2011

Pharmaceutical Research, Feb 22, 2008

Prostaglandins have potent and diverse biologic activities, but their clinical application is sev... more Prostaglandins have potent and diverse biologic activities, but their clinical application is severely restricted, mainly due to rapid inactivation in vivo. In order to modulate the pharmacokinetics of prostaglandin E(1) (PGE(1)), we prepared biodegradable nanoparticles as a drug carrier. Nanoparticles encapsulating PGE(1) were prepared from a blend of poly(lactic acid) homopolymer and poly(ethylene glycol)-poly(lactide) block copolymer by the solvent diffusion method in the presence of iron. PGE(1) was efficiently and stably embedded in the nanoparticles through interaction with iron, despite being relatively hydrophilic and having unstable chemical properties. Depending on the isomers and molecular weight of poly(lactic acid) selected, PGE(1) was gradually released from the nanoparticles at various rates into diluted serum in vitro. Both stable retention of PGE(1) in the nanoparticles and coating of the nanoparticles with poly(ethylene glycol) led to an extremely extended blood residence time of PGE(1), as well as preferential accumulation in vascular lesions. These results suggest that the present strategy is useful to advance the clinical application of PGE(1) as a therapeutic agent for vascular disorders.

Pharmaceutical Research, Jul 25, 2009

Journal of St. Marianna University, Dec 1, 2011

Journal of Pharmacy and Pharmacology, Sep 1, 2002

Journal of Controlled Release, Feb 19, 2002

To ensure a strictly controlled release of insulin, a preparation method for insulin-loaded micro... more To ensure a strictly controlled release of insulin, a preparation method for insulin-loaded microcapsules was designed. Microcapsules were prepared with an injectable, biodegradable polymer composed of co-poly(D,L-lactic/glycolic) acids (PLGA) (mean molecular weight 6600, LA/GA ratio 50:50). Morphological examination using scanning electron microphotography demonstrated spherical particles with a main diameter of 15-30 microm. When 3% insulin-loaded PLGA microcapsules were administered subcutaneously as a single dose (250 U/kg) to streptozotocin-induced hyperglycemic rats, plasma insulin levels increased and were sustained at levels showing hypoglycemic effects. When glycerin, ethanol, or distilled water was used throughout the preparation procedure, the resultant microcapsules dramatically reduced the initial burst. The formulation in which glycerin was added to an oil phase containing PLGA, insulin, and ZnO increased plasma insulin levels to 86.7, 108.4, and 84.9 microU/ml at 1, 2, and 6 h, respectively. The levels remained at 36.2-140.7 microU/ml from day 1 to day 9. The AUC(0-24 h)/AUC(0-336 h) ratio was calculated to be 9.7%. The formulation prepared without additives gave such a rapid insulin release that animals receiving it became transiently hypoglycemic.

Journal of Controlled Release, 1994