Lipo-prostaglandin preparations

Abstract

With advances in medicine and pharmaceutical science, many potent biologically active substances have been introduced into clinical practice. The substances include prostaglandins, cytokines, and other active polypeptides. These potent biological substances are often produced and act locally in the body. However, as exogenous drugs they may cause many problems. For example, prostaglandins are produced locally as needed, and they act locally. After they enter into systemic circulation, they are rapidly metabolized. This rapid metabolism is believed to suppress systemic adverse reactions. However, exogenous prostaglandins are often administered continuously and at high dose to obtain sufficient effects. When prostaglandins are administered in this way, their pharmacological actions affect the whole body, and as a result, various adverse reactions develop. PGE, (prostaglandin Et) and other prostaglandins are often irritant, and may cause pain, inflammatory changes, and other local reactions at the site of injection. To solve these problems, it has been hoped that drug delivery systems, particularly targeted delivery, would be developed for prostaglandin treatment. PGEl and PGIz (prostacyclin) are known to be very valuable for the treatment of many arteriosclerotic diseases, such as peripheral vascular diseases (1)) ischemic heart diseases, cerebrovascular diseases, and other microcirculatory disturbances, if they can be free from adverse reactions. A suitable carrier is therefore needed to bring sufficient drug to the lesion site. Liposomes have been studied for a long time as possible drug carriers. There is evidence that both response to, and the safety of drugs increases when they are incorporated in liposomes (2, 3). However, the practical use of liposomes has been delayed because of difficulties in mass production, sterilization, stability, and safety: So, since 1980, we have attempted to use lipid microspheres (LM, lipid emulsion), which had already been in clinical use, instead of liposomes, as a better drug carrier (4, 5, 6). Large amounts of lipid microspheres have been used under the name of Intralipid for almost 50 years (7). So, although only lipophilic drugs are incorporated, as a drug carrier they are virtually free from any concern with regard to safety, stability, sterilization, and mass production. Lipid microspheres were previously suspected of inducing susceptibility to infection (8, 9), but subsequent studies proved that this suspicion was not justified. Fortunately, prostaglandins are highly lipophilic, and work at very low concentrations. Thus, they are very suitable for incorporation into lipid microspheres.