title: Preservation of Anticancer and Immunosuppressive Properties of Rapamycin Achieved Through Controlled Releasing Particles.
abstract: Rapamycin is commonly used in chemotherapy and posttransplantation rejection suppression, where sustained release is preferred. Conventionally, rapamycin has to be administered in excess due to its poor solubility, and this often leads to cytotoxicity and undesirable side effects. In addition, rapamycin has been shown to be hydrolytically unstable, losing its bioactivity within a few hours. The use of drug delivery systems is hypothesized to preserve the bioactivity of rapamycin, while providing controlled release of this otherwise potent drug. This paper reports on the use of microparticles (MP) as a means to tune and sustain the delivery of bioactive rapamycin for up to 30 days. Rapamycin was encapsulated (100% efficiency) in poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or a mixture of both via an emulsion method. The use of different polymer types and mixture was shown to achieve a variety of release kinetics and profile. Released rapamycin was subsequently evaluated against breast cancer cell (MCF-7) and human lymphocyte cell (Jurkat). Inhibition of cell proliferation was in good agreement with in vitro release profiles, which confirmed the intact bioactivity of rapamycin. For Jurkat cells, the suppression of cell growth was proven to be effective up to 20 days, a duration significantly longer than free rapamycin. Taken together, these results demonstrate the ability to tune, sustain, and preserve the bioactivity of rapamycin using MP formulations. The sustained delivery of rapamycin could lead to better therapeutic effects than bolus dosage, at the same time improving patient compliance due to its long-acting duration.
authors.affiliation: Nanyang Institute of Technology in Health & Medicine, Interdisciplinary Graduate School, Nanyang Technological University, Singapore, Singapore.|School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
authors.forename: Yan Liang
authors.initials: YL
authors.lastname: Fan
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
authors.forename: Han Wei
authors.initials: HW
authors.lastname: Hou
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
authors.forename: Hui Min
authors.initials: HM
authors.lastname: Tay
authors.affiliation: The Agency for Science, Technology and Research, Biotransformation Innovation Platform, Singapore, Singapore.
authors.forename: Wei Mei
authors.initials: WM
authors.lastname: Guo
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.|The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.affiliation: School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore. joachimloo@ntu.edu.sg.|Singapore Centre for Environmental Life Sciences Engineering, Singapore, Singapore. joachimloo@ntu.edu.sg.
authors.forename: Say Chye Joachim
authors.initials: SCJ
authors.lastname: Loo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D019169:Jurkat Cells; D061986:MCF-7 Cells; D020123:Sirolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D020123:Sirolimus
keywords: drug delivery; microparticle; rapamycin; sustained release