Research Information

HOMEResearch InformationResearch Contents

Research Contents

PLGA Nano-particle = Effective, Safe, and reliable

  • PLGA(poly lactic-co-glycolic acid) was approved for use in animals as well as for human consumption from FDA.
  • We succeeded in formulating fat soluble drugs and compounds in nanoparticles.
  • PLGA has the very high transfer efficiency into the cells, and it was confirmed that nanoformulated drugs are released gradually.

Hydrolysis Process of PLGA in vivo

PLGA does not accumulate in a living organism and is extremely safe because it undergoes hydrolysis to produce lactic and glycol acids which are eventually eliminated from the body in the form of carbon dioxide and water.

SP-001
(Pitavastatin-encapsulated PLGA nanoparticles)
Minimally invasive treatment
Minimally invasive treatment

Target disease
Chronic critical limb ischemia・Acute Myocardiac Infarction
Severe pulmonary arterial hypertension

Arteriosclerosis obliterans is a disease that reduces the quality of life of patients and denotes a poor-prognosis. The survival rate of patients with critical limb ischemia is quite poor (1 year mortality rate: 25%), which is lower than the mean survival rate of cancer patients.
Since an effective therapy has not been developed yet, our pitavastatin-encapsulated PLGA nanoparticle has attracted considerable attentions as a highly innovative invention.
Statins have the protective effects on the cardiovascular system and have been known to be effective in the improvement of cardiovascular function, the improvement of ischemia by promoting cardiovascular neogenesis, the stabilization and regression of atherosclerotic plaque with anti-inflammatory effect, and the improvement of ischemia-reperfusion injury. However, statins theoretically need a dose more than 30 times higher than the clinical dose in order to see the expected effects mentioned above. For this reason, statins have not been used as an oral drug.
There is an enormous potential in nanoformulation techniques to optimize and maximize the protective effects of statins on the cardiovascular system with small doses. We believe that statins could be delivered into the vascular endothelial cells at the affected area by using a nano-DDS technology, and our research continues with this belief.

The birth of pitavastatin-encapsulated PLGA nanoparticles

The intramuscular injection of pitavastatin-encapsulated PLGA nanoparticles may improve the blood flow at the limb ischemia and avoid lower limb amputation. Currently, the investigator-initiated clinical trial of pitavastatin-encapsulated PLGA nanoparticles has been conducted at Kyushu University Hospital. This treatment may provide a relief of pain at rest and improve ischemic ulcer.
The selective delivery of pitavastatin-encapsulated PLGA nanoparticles into the vascular endothelial cells at the affected area is expected to induce neovascularization at a dose 300 times less than the usual recommended dose.

In addition, the pitavastatin-encapsulated PLGA nanoparticles may be applied to the treatment for ischemic heart diseases without effective pharmaceuticals, such as acute myocardial infarction, angina pectoris and cardiac insufficiency.

We have demonstrated therapeutic effects of pitavastatin-encapsulated PLGA nanoparticles on severe pulmonary arterial hypertension of an intractable and rare disease in the pulmonary hypertension model animals (acquisition of nonclinical POC).
Pitavastatin-encapsulated PLGA nanoparticles may be delivered to the culprit lesion in the lung by the intratracheal or intravenous administration, which will lead to healing as well as suppress the progression of pulmonary arteriole.
In the previous nonclinical studies, we have revealed the marked improvement of clinical conditions by administration of pitavastatin-encapsulated PLGA nanoparticles, indicating that application of pitavastatin-encapsulated PLGA nanoparticles can be expanded to the treatment of other pulmonary diseases, including secondary pulmonary hypertension and chronic obstructive pulmonary disease (COPD). Therefore, the research and development of pitavastatin-encapsulated PLGA nanoparticle formulations is of critical importance from the aspect of clinical research and marketability.

SP-002(Cyclosporine nanoparticle formulation)Minimally invasive treatment

Target disease
Acute myocardial infarction, stroke

Acute myocardial infarction and cerebral infarction are the leading causes of death in the world. Under the circumstances, many people have aftereffects from these diseases. The most critical prognostic determinant of the extent of aftereffects is reported to be an infarct size. “Reperfusion therapy (blood flow is restarted to break ischemia), so-called percutaneous coronary intervention” is performed as the most suitable medical treatment, but the effects of the therapy are insufficient yet. Thus, the long-term prognosis has not been improved. “Ischemia-reperfusion injury” is the phenomena occurred at the reperfusion therapy. When the cell necrosis occurs in the infraction site due to the long-term inhibition of blood flow (ischemia), active oxygen species are generated at the necrotic area even if blood flow is restarted, which cause damage to the cells. This is called “ischemia-reperfusion injury”.

The ischemia-reperfusion injury is attributable to the mitochondrial damage and infiltration of activated monocytes. However, most of the treatments for ischemia-reperfusion injury target either one of them, and thus any treatment has not been sufficient. Our company has succeeded the development of the technology that allows the drug to reach the mitochondria and the monocytes simultaneously. The nonclinical studies demonstrated that an intravenous administration of cyclosporine nanoparticle formulation at the reperfusion therapy dramatically reduced infarct size.

The birth of cyclosporine nanoparticle formulation

Reperfusion area (red) - an infarct site (white)Selective nanoDDS

SP-003
(Gamma-oryzanol nanoparticle formulation)
Functional food・drug

Target disease
Diabetes・obesity

As westernized diets are getting popular, obesity and metabolic syndrome have been increasing rapidly in Japan, which results in a tendency for a significant increase in the number of patients with lifestyle-related diseases.
In fiscal 2011, medical costs for lifestyle-related diseases accounted for one third of the entire medical care expenditure (approximately 9.8 trillion yen) (Overview of FY 2011 National Medical Care Expenditure, the Ministry of Health, Labor and Welfare).
Lifestyle-related diseases are hard to cure and often require a considerable amount of medical costs. Therefore, they are becoming a major factor that makes an increase in the medical costs. According to the official report of the Ministry of Health, Labor and Welfare, the national medical care expenditure in Japan have gone on increasing, and will run into approximately 60 trillion yen in fiscal 2025.

Based on these incidents, we thought that it is important for individuals to actively undertake in promoting their own health and prevent their own disease. In the joint project with the research institutions including the Second Department of Internal Medicine, University of the Ryukyu Medical School, we have successfully optimized nanoparticles containing gamma-oryzanol in brown rice which is effective in improving obesity, glycolipid metabolism, fatty liver and vascular endothelium function.

*Okinawa Prefecture Fiscal 2014 “Life Science Network Formation Project”

The birth of gamma-oryzanol nanoparticle formation

Indications

In order to treat obesity, metabolic syndrome, diabetes or abnormal lipid metabolism, high-dose intakes of gamma-oryzanol (a dosage in case of 60 kg body weights; 320 mg×60 = 19.2 g) are required. However, our optimized gamma-oryzanol nanoparticle formulations can reduce the intake amount to 0.1 % or less.
Currently, we have a new project collaborating with Kyusyu University and University of the Ryukyus, and have been promoting research and development in order to put the nanoformulation technology into practical use.

*NEDO Fiscal 2015 “Collaborative Promotion Project to Create Innovative Monozukuri
(Manufacturing) Industry”

Blood glucose level(mg/dl)Weight(g)
Nautial fat(mg/dl)Inflammation