The Drug Delivery System (DDS) is a technology enabling drugs to be optimally delivered with regard to a specified site, period, and amount.
GaleniSearch Laboratories (GSL) focused on research and development of DDS concerning the period and the amount of drugs, that is, a sustained release DDS.
Specifically, it is a technology to maintain effective levels in the human body by a controlled release of drugs from the system and to sustain its efficacy for long periods of time after a single administration. GSL makes every effort to contribute to the health of people and the welfare of society by realizing this simple concept. ■To maximize the value of the drugs ■To minimize the patient’burden
　by reducing the frequency of dosage and adverse effects ■To improve medical economic efficiency Simple is best…
Diverse kinds of original sustained release systems,
combination of various drugs with the original system,
…Sustained release DDS technology is expanding the possibilities for multiple applications.

〜The needs for sustained release systems of protein drugs〜

Proteins have various physiological functions, some of which have been used as drugs thanks to great progress in genetic engineering. Additionally, it is likely that new protein is discovered from genes which has been unknown so far, owing to the mapping of the entire human gene sequence. It is expected that numerous pharmacologically active proteins will be discovered among the new proteins and the number of protein-derived drugs will increase from the future.

Generally speaking, protein-derived drugs are not absorbed in the digestive tract, and they are unstable and rapidly eliminated from the human body. Accordingly, patients need daily injections for medication, which is inconvenient for the patients and medical staff. Therefore, diverse kinds of DDS for proteins and peptides are being studied.

The sustained release system using porous microparticles, a core technology GSL developed, is a DDS technology that covers previous defects and makes full use of protein drugs.

→The example is here

What is GaleniSearch Laboratories’DDS?

GaleniSearch Laboratories has currently developed two types of DDS.

The first one is a sustained release for protein, and that is injected in for subcutaneous site and hydroxyapatite derivative(HAp-Z) is used as a carrier.
The other is a sustained release of adherent time-released system and that is administered to the topical target site. The system is coated by a adhesive polymer on the carrier, PLGA. The coated microparticles can adhere on the mucous membrane of the target site to release the drug for a specific period.

A drug incorporated in a microparticles carrier prepared with HAp-Z or PLGA showed controlled release and maintenance of the effective levels in the human body for long period. It is expected that the controlled release DDS will be medically beneficial.

Superior Features

The two microparticles are bioerodible and it is possible to control the release period of the drug with the elimination rate.

As for the HAp-Z, we use the porous microparticles developed by the National Institute for Material Science (NIMS). HAp-Z is the main component of bones and teeth and is biocompatible. As for PLGA, it has already been used in humans world wide.

Because protein drugs are unstable and eliminated rapidly from the human body, a daily injection is required for medication. Moreover, the protein drugs are often denatured through the fabrication process. We overcame the problems concerning denaturing by the use of the specified fabrication process which is prepared in an aqueous solusion.

The average particle size of HAp-Z used is about 8 μm, while that of PLGA is about 20μm. Both of them are high dispersible and can easily pass through a fine needle, which minimizes the patient’pain on receiving the injection.

We have various microparticle DDS systems. We can design by choice an optimal microparticle system according to the chemical structure and physicochemical properties of various drugs.

A microparticle sustained release system, which slowly releases a drug at the target sites, is obtained by coating an adhesive polymer onto the surface of the microparticles. This DDS is called the Adherent Time-Released System and is useful for topical applications such as for nasal and buccal sites.

The human growth hormone (hGH) is a protein secreted from the pituitary gland, and it is essential for human growth. When this protein is lacking, one is likely to develop such conditions as dwarfism. We have already established the sustained release system of hGH as one of the core technologies.

This is a system in which hGH and an additive are incorporated in porous HAp-Z microparticles, and the microparticles are coated with a water-compatible and biodegradable polymer. The average microparticle diameter is 8 μm. The system can easily be injected through 27G injection needles, and contains 15(w/w) % of hGH. After the system is suspended in an aqueous solution, the suspension is subcutaneously injected. It is deposited at the injection site, and gradually releases incorporated hGH to the blood through the tissues.

One of the proper methods of evaluating the releasability is to measure the plasma level profiles. After a single injection of the system to immunosuppressive rats, the blood levels of hGH showed a high level from the initial burst release and then followed a steady level for over 2 weeks. This means that hGH is released at a constant rate for over 2 weeks from the microparticle system, thus meaning that the steady level was effective.
It has already been confirmed that porous HAp-Z microparticles did not remain at the injection site after a few weeks. This means that this system is bioerodible. Similar results were observed in monkeys.

One of the methods used to evaluate the pharmacological effect of the system is to monitor the body weight gain after administration of the system to pituitectomized rats. The body weight of pituitectomized rats after a single injection of the system increased for three weeks, following which a body weight gain was minimal because hGH in the system was depleted. On the other hand, an increase in body weight was not observed over the full time period in the untreated control group.

Coating of the microparticles with muco-adhesive polymer enables them to adhere to mucosal sites and to continuously release the drug in the system around the diseased area. This will mean the first order targeting of the drug. It is expected that the drug acts more effectively while the side effects for the whole body are reduced. This is the objective of this system.

The surface of PLGA (copoly(lactic/glycolic)acid) particle encapsulated drug should be coated with the muco-adhesive polymer. As shown in the following photomicrograph, the microparticles have the surface coated uniformly with the new method devised by GaleniSearch Laboratories. This system should be squeezed through by using, for example, a thin tube, or applied directly to the diseased site, and then adhered at the mucus; the drug is released at the topical site for the sustained-release term.

The following figure shows the results of an experiment where the system particles were applied on the mucosa of the rat reversed intestine and incubated at 37℃ for several hours; then, after the intestine was washed, the remaining drug adhered in the intestine was determined. In comparison to the control without a coating, the drug in this system coated by our technology remained at the 80% level, which shows it has great adherability.

Title	Application Date
	Published Number
	Patent Number
Sustained release microparticles of hGH	18 June 2003(Japan), 15 June 2004(PCT)
	2005-8545(Japan), WO2004/112827A1(PCT)
	3915001(Japan), ZL200480013106.X.(China)
Sustained release microparticles of protein	11 June 2004(PCT)
	WO2004/112751A1
Protein drug sustained release microparticles	27 January 2005(PCT)
	WO2005/082405A1
Preparation method of sustained release microparticles	27 October 2006(Japan)
Preparation method of sustained release nanoparticles of G-CSF	16 April 2008(Japan)
Adhesive microcapsule	9 March 2006(Japan), 27 February 2007(PCT)
	WO2007/102447A1
Preparation method of adhesive microparticles	26 April 2007(Japan)
Preparation method of adhesive microparticles	16 April 2008(Japan)