Liquid filled nanoparticles as a drug delivery tool for protein therapeutics.
In the present study, an attempt was made to study the feasibility of nanoparticulate adsorbents in the presence of an absorption enhancer, as a drug delivery tool for the administration of erythropoietin (EPO) to the small intestine. Liquid filled nano- and micro-particles (LFNPS/LFMPS) were prepared using solid adsorbents such as porous silicon dioxide (Sylysia 550), carbon nanotubes (CNTs), carbon nanohorns, fullerene, charcoal and bamboo charcoal. Surfactants such as a saturated polyglycolysed C8-C18 glyceride (Gelucire 44/14), PEG-8 capryl/caprylic acid glycerides (Labrasol) and polyoxyethylene hydrogenated castor oil derivative (HCO-60) were used as an absorption enhancer at 50mg/kg along with casein/lactoferrin as enzyme inhibitors. The absorption of EPO was studied by measuring serum EPO levels by an ELISA method after small intestinal administration of EPO-LFNPS preparation to rats at the EPO dose level of 100 IU/kg. Among the adsorbents studied, CNTs showed the highest serum EPO level of 62.7 +/- 11.6 mIU/ml. In addition, with the use of casein, EPO absorption was improved, C(max) 143.1 +/- 15.2 mIU/ml. Labrasol showed the highest absorption enhancing effect after intra-jejunum administration than Gelucire 44/14 and HCO-60, 25.6 +/- 3.2 and 22.2 +/- 3.6 mIU/ml, respectively. Jejunum was found to be the best absorption site for the absorption of EPO from LFNPS. The use of CNTs as LFNPS, improved the bioavailability of EPO to 11.5% following intra-small intestinal administration.
Venkatesan
Natarajan
N
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Japan. takada@mb.kyoto-phu.ac.jp
Yoshimitsu
Junichiro
J
Ito
Yukako
Y
Shibata
Nobuhito
N
Takada
Kanji
K
D000042:Absorption; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D007421:Intestine, Small / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008422:Materials Testing; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D012996:Solutions; D004921:Erythropoietin