title: Incorporation into a biodegradable hyaluronic acid matrix enhances in vivo efficacy of recombinant human interleukin 11 (rhIL11).
abstract: 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.
authors.affiliation: 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>
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamashita
authors.forename: Tatsunobu
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Takaishi
authors.forename: Kiyo
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takemura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Maeda
authors.forename: Katsumi
authors.initials: K
authors.lastname: Saito
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Takakura
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: 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
chemical_list: D017370:Interleukin-11; D011994:Recombinant Proteins; D006820:Hyaluronic Acid