Future drug delivery research in South Korea.
According to the Science Citation Index database, over 50 papers related to drug delivery have been published from South Korea during the last 3 years. For the purpose of this presentation, some of the recently carried out research in our department will be introduced and future research directions presented. Proliposomes are free flowing particles which are composed of drugs, phospholipids and a water soluble porous powder, and immediately form a liposomal dispersion upon hydration. The preparation can be stored sterilized in a dried state and, by controlling the size of the porous powder in proliposomes, relatively narrow range of reconstituted liposome size can be obtained. Because of these properties, proliposomes appear to be a potential alternative to liposomes in design and fabrication of liposomal dosage forms. Thus, we tested the feasibility of this preparation as a sustained transdermal dosage form. Proliposomes containing varying amount of nicotine, a model drug, were prepared using sorbitol and lecithin. Microscopic observation revealed that this preparation is converted to liposomes almost completely within minutes following contact with water. The release pattern of the model drug from this preparation was apparently similar to that of the Exodus((R)) patch, a commercially available transdermal nicotine formulation. Compared with nicotine powder, the nicotine flux across rat skin from proliposomes was initially retarded, and appeared to remain constant. This observation indicated that sustained transdermal delivery of nicotine is feasible using proliposomal formulations under occluded condition. In addition to the investigation of the potential application of proliposomes, we were also interested in the role of the stratum corneum (SC) in the enhanced delivery of drugs from liposomes. Thus, liposome-gel formulation containing hydrocortisone (HC), a model hydrophobic drug, was prepared and used in this study. The study was carried out on both normal and stratum corneum removed skins. Percutaneous absorption of HC across SC removed skin was significantly faster than that across normal skin, suggesting that SC behaves as a penetration barrier for the liposome-bound drugs. Interestingly, the liposome-gel in this study reduced the skin absorption of HC, compared with the conventional ointment formulation. The amount of HC absorbed from the liposome-gel after 8 h into the SC-removed skin was less than one third of that from the conventional ointment. Despite the reduced absorption, a higher and sustained skin concentrations of HC were achieved for the liposome-gel. Drug concentration in both viable and deep skin reached a maximum within 0.5 h. However, drug concentrations in these tissues declined as a function of time for conventional ointment, while those from the liposome-gel were greatly sustained, resulting in a 5-fold higher viable skin drug level was obtained at 8 h after the application. In contrast, plasma concentration of HC at 4 h from the liposome-gel was only one-fourth the value from the conventional ointment in the SC-removed skin. Therefore, the higher and sustained drug concentration in the viable skin appeared not to be due to the enhanced percutaneous absorption but due to retarded diffusion of the drug from the skin.
Chung
S J
SJ
Department of Pharmaceutics, Seoul National University, San 56-1, Shinlim-dong, Kwanak-gu, Seoul, South Korea.
D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000639:trends*; D005544:Forecasting; D007723:Korea; D008081:Liposomes; D008297:Male; D009538:Nicotine / Q000008:administration & dosage; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012106:Research / Q000639:trends*; D012869:Skin Absorption
D004337:Drug Carriers; D008081:Liposomes; D009538:Nicotine