Liquid filled nanoparticles as a drug delivery tool for protein therapeutics

被引:137
作者
Venkatesan, N [1 ]
Yoshimitsu, J [1 ]
Ito, Y [1 ]
Shibata, N [1 ]
Takada, K [1 ]
机构
[1] Kyoto Pharmaceut Univ, Dept Pharmacocinet, Yamashina Ku, Kyoto 6078414, Japan
关键词
erythropoietin; carbon nanotubes; labrasol; gelucire; 44/14; HCO-60; nanoparticles;
D O I
10.1016/j.biomaterials.2005.05.012
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
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 50 mg/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/mI. 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. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:7154 / 7163
页数:10
相关论文
共 55 条
[1]   CAPILLARITY-INDUCED FILLING OF CARBON NANOTUBES [J].
AJAYAN, PM ;
IIJIMA, S .
NATURE, 1993, 361 (6410) :333-334
[2]   OPENING CARBON NANOTUBES WITH OXYGEN AND IMPLICATIONS FOR FILLING [J].
AJAYAN, PM ;
EBBESEN, TW ;
ICHIHASHI, T ;
IIJIMA, S ;
TANIGAKI, K ;
HIURA, H .
NATURE, 1993, 362 (6420) :522-525
[3]   Amphiphilic vehicles improve the oral bioavailability of a poorly soluble HIV protease inhibitor at high doses [J].
Aungst, BJ ;
Nguyen, NH ;
Rogers, NJ ;
Rowe, SM ;
Hussain, MA ;
White, SJ ;
Shum, L .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1997, 156 (01) :79-88
[4]   An investigation into the structure and bioavailability of α-tocopherol dispersions in Gelucire 44/14 [J].
Barker, SA ;
Yap, SP ;
Yuen, KH ;
McCoy, CP ;
Murphy, JR ;
Craig, DQM .
JOURNAL OF CONTROLLED RELEASE, 2003, 91 (03) :477-488
[5]   Carbon nanotubes - the route toward applications [J].
Baughman, RH ;
Zakhidov, AA ;
de Heer, WA .
SCIENCE, 2002, 297 (5582) :787-792
[6]   Electronic and structural properties of carbon nanohorns [J].
Berber, S ;
Kwon, YK ;
Tománek, D .
PHYSICAL REVIEW B, 2000, 62 (04) :R2291-R2294
[7]   Biomedical applications of functionalised carbon nanotubes [J].
Bianco, A ;
Kostarelos, K ;
Partidos, CD ;
Prato, M .
CHEMICAL COMMUNICATIONS, 2005, (05) :571-577
[8]  
Craig Duncan Q. M., 1995, P148
[9]   NANOCAPSULES AS CARRIERS FOR ORAL PEPTIDE DELIVERY [J].
DAMGE, C ;
MICHEL, C ;
APRAHAMIAN, M ;
COUVREUR, P ;
DEVISSAGUET, JP .
JOURNAL OF CONTROLLED RELEASE, 1990, 13 (2-3) :233-239
[10]   CHARACTERIZATION OF RECOMBINANT-HUMAN-ERYTHROPOIETIN PRODUCED IN CHINESE-HAMSTER OVARY CELLS [J].
DAVIS, JM ;
ARAKAWA, T ;
STRICKLAND, TW ;
YPHANTIS, DA .
BIOCHEMISTRY, 1987, 26 (09) :2633-2638