title: Long-term sustained-released in situ gels of a water-insoluble drug amphotericin B for mycotic arthritis intra-articular administration: preparation, in vitro and in vivo evaluation.
abstract: Amphotericin B (AMB) was often used in intra-articular injection administration for fungal arthritis, because it could often bring a satisfactory therapeutic efficacy and a minimum systemic toxic side effect. However, because of the multiple operations and the frequent injections, the compliance of the patients was bad. Therefore, to develop a long-term sustained-released preparation of AMB for mycotic arthritis intra-articular administration is of great significance. The purpose of present study was to develop a long-term sustained-released in situ gel of a water-insoluble drug AMB for mycotic arthritis intra-articular administration. Based on the evaluations of the in vitro properties of the formulations, the formulation containing 10% (w/w) ethanol, 15% (w/w) PG, 0.75% (w/w) HA, 5% (w/w) purified soybean oil, 0.03% (w/w) α-tocopherol, 15% (w/w) water and 55% (w/w) glyceryl monooleate was selected as a suitable intra-articular injectable in situ gel drug delivery system for water-insoluble drug AMB. Furthermore, the results of the in vivo study on rabbits showed that the selected formulation was a safe and effective long-term sustained-released intra-articular injectable AMB preparation. Therefore, the presented in situ AMB gel could reduce the frequency of the administration in the AMB treatment of fungal arthritis, and then would get a good patient compliance.
authors: Department of Pharmacy and.
authors: Guo
authors: G
authors: Shan-Bin
authors: Tian
authors: T
authors: Yue
authors: Jian
authors: J
authors: Ling-Yan
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics; D001170:Arthritis, Infectious / Q000188:drug therapy; D001682:Biological Availability; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D055119:Elastic Modulus; D005079:Excipients / Q000737:chemistry; D005782:Gels; D005989:Glycerides / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry; D007270:Injections, Intra-Articular; D009181:Mycoses / Q000188:drug therapy; D011817:Rabbits; D011897:Random Allocation; D013582:Synovial Fluid / Q000737:chemistry*; D014783:Viscosity
chemical_list: D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D005989:Glycerides; D000666:Amphotericin B; D006820:Hyaluronic Acid; C005953:monoolein
keywords: Amphotericin B; fungal arthritis; glyceryl monooleate; injectable gel; intra-articular; sustained release