Pharmacokinetic change of nanoparticulate formulation "Lactosome" on multiple administrations.
ABSTRACT Lactosome, which is a polymer micelle composed of poly(lactic acid)-b-poly(sarcosine), was applied successfully for solid tumor imaging. Lactosome is considered to escape from the reticuloendothelial system recognition, and shows prolonged in vivo blood clearance time. In vivo disposition of Lactosome, however, changed upon multiple dosages. Lactosome at the 2nd dosage was cleared from the blood stream by trapping at liver. This accelerated blood clearance (ABC) phenomenon is explained by production of anti-Lactosome IgM and IgG(3) through the immune response related with B-lymphocyte cells. The memory effect of B-lymphocyte cells lasted nearly for six months in mouse. The epitope moiety of Lactosome is concluded to be poly(sarcosine) based on the competitive inhibition assay. Since the ABC phenomenon was also reported with PEGylated liposome, nanoparticles in general may be potential in triggering the immune system.
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ABSTRACT: Polymer nanoparticles can be prepared by self-assembling of amphiphilic polymers, and various types of molecular assemblies have been reported. In particular, in medicinal fields, utilization of these polymer nanoparticles as carriers for drug delivery system (DDS) has been actively tried, and some nanoparticulate drugs are currently under preclinical evaluations. A radionuclide is an unstable nucleus and decays with emission of radioactive rays, which can be utilized as a tracer in the diagnostic imaging systems of PET and SPECT and also in therapeutic purposes. Since polymer nanoparticles can encapsulate most of diagnostic and therapeutic agents with a proper design of amphiphilic polymers, they should be effective DDS carriers of radionuclides in the nuclear medicinal field. Indeed, nanoparticles have been recently attracting much attention as common platform carriers for diagnostic and therapeutic drugs and contribute to the development of nanotheranostics. In this paper, recent developments of solid tumor-targeting polymer nanoparticles in nuclear medicinal fields are reviewed.TheScientificWorldJournal. 01/2014; 2014:424513.
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ABSTRACT: Nanoparticles are expected to be applicable for the theranostics as a carrier of the diagnostic and therapeutic agents. Lactosome is a polymeric micelle composed of amphiphilic polydepsipeptide, poly(sarcosine)64-block-poly(l-lactic acid)30, which was found to accumulate in solid tumors through the enhanced permeability and retention effect. However, lactosome was captured by liver on the second administration to a mouse. This phenomenon is called as the accelerated blood clearance phenomenon. On the other hand, peptide-nanosheet composed of amphiphilic polypeptide, poly(sarcosine)60-block-(l-Leu-Aib)6, where the poly(l-lactic acid) block in lactosome was replaced with the (l-Leu-Aib)6 block, abolished the accelerated blood clearance phenomenon. The ELISA and in vivo near-infrared fluorescence imaging revealed that peptide-nanosheets did not activate the immune system despite the same hydrophilic block being used. The high surface density of poly(sarcosine) chains on the peptide-nanosheet may be one of the causes of the suppressive immune response. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.Journal of Peptide Science 05/2014; 20(7). · 1.86 Impact Factor
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ABSTRACT: Lactosome is a polymeric micelle composed of amphiphilic polydepsipeptide, poly(sarcosine)64-block-poly(l-lactic acid)30 (AB-type), which accumulates in solid tumors through the enhanced permeability and retention (EPR) effect. However, lactosome on multiple administrations changed its pharmacokinetics from accumulation in tumors to liver due to the production of antilactosome IgM, which was triggered by the first administration. This phenomenon is called the accelerated blood clearance (ABC). In order to reduce the production of antilactosome IgM, a novel nanoparticle composed of (poly(sarcosine)23)3-block-poly(l-lactic acid)30 (A3B-type) was prepared. The A3B-type lactosome at the second administration showed an in vivo disposition similar to that at the first administration due to suppression of antibody production. This study involving the AB- and A3B-type lactosomes, with variation of conditions, revealed that the high local density of poly(sarcosine) chains of the A3B-type lactosome should relate to the prevention of a polymeric micelle from interacting B-cell receptors.ACS Medicinal Chemistry Letters 08/2014; 5(8):873-7. · 3.07 Impact Factor