title: Development of Intra-knee Joint Sustained-Release Gel Formulation and Evaluation of Its Pharmacological Efficiency in Rats.
abstract: In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University.|Faculty of Pharmacy, Meijo University.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Noda
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Okuda
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ban
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Ryota
authors.initials: R
authors.lastname: Mizuno
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tagami
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya City University.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ozeki
authors.affiliation: Faculty of Pharmacy, Meijo University.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Okamoto
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin; D004396:Coloring Agents / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000494:pharmacology; D005782:Gels; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D007208:Indocyanine Green / Q000008:administration & dosage; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D016138:Walking
chemical_list: D000700:Analgesics; D004396:Coloring Agents; D003692:Delayed-Action Preparations; D005782:Gels; D006820:Hyaluronic Acid; D007208:Indocyanine Green; D001920:Bradykinin
keywords: gel formulation; hyaluronic acid; intra-articular injection; sustained release