Incorporation into a biodegradable hyaluronic acid matrix enhances in vivo efficacy of recombinant human interleukin 11 (rhIL11).
In order to improve the therapeutic efficacy of recombinant human interleukin 11 (rhIL11) and to reduce its frequency of administration, the feasibility of a sustained release formulation consisting of hyaluronic acid (HyA) was investigated. rhIL11 was mixed together with an aqueous solution of HyA or HyA and protamine, and the mixture was lyophilized. The resulting powder was compressed into pellet and was subcutaneously administered in the rats. The plasma profile of rhIL11 was determined by ELISA. The mean residence time and t(max) of rhIL11 were much prolonged by administration in an HyA pellet. The additional incorporation of protamine into the formulation further enhanced the plasma duration of the protein. Separately, peripheral platelet counts were measured for several rhIL11-containing solution and pellets. Platelet counts much increased after administration of rhIL11-containing pellets, whereas the effect of bolus subcutaneous administration of rhIL11 solution was limited. The degree of platelet increase in rats treated with the pellets was comparable to that for rats treated with 1- or 2-day continuous infusion from an osmotic mini-pump; these data reflect the importance of increased plasma duration of rhIL11. These data indicate that use of hyaluronic acid as a polymer matrix might enhance the therapeutic efficacy of rhIL11.
Takagi
Akira
A
Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., 180 Ozumi, Yaizu, Shizuoka 425-0072, Japan. akira-takagi@jp.astellas.com <akira-takagi@jp.astellas.com>
Yamashita
Noboru
N
Yoshioka
Tatsunobu
T
Takaishi
Yuuki
Y
Nakanishi
Kiyo
K
Takemura
Shigeo
S
Maeda
Atsushi
A
Saito
Katsumi
K
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D004305:Dose-Response Relationship, Drug; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D017370:Interleukin-11 / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D017370:Interleukin-11; D011994:Recombinant Proteins; D006820:Hyaluronic Acid