title: Preparation and evaluation of a novel biodegradable long-acting intravitreal implant containing ligustrazine for the treatment of proliferative vitreoretinopathy.
abstract: OBJECTIVE
  It is challenging to deliver the therapeutic drug effectively to the posterior ocular disease location with optimized exposure and long-term effects when treating proliferative vitreoretinopathy (PVR). The objective of this study is to develop a novel biodegradable and long-acting ocular implant for PVR therapy with ligustrazine as the active ingredient.
  
  
  METHODS
  The ligustrazine implants were prepared with poly(DL-lactide-co-glycolide) using a hot-melting extrusion. The physicochemical properties of the implants were characterized. The effectiveness of the selected ligustrazine implants was evaluated in a PVR rabbit model. Furthermore, the in-vitro drug release profile and pharmacokinetics were compared, and in-vitro/in-vivo correlations were evaluated.
  
  
  RESULTS
  The optimal implants had an ideal zero-order in-vitro drug release profile, which was correlated with the in-vivo drug absorption fraction in the vitreous bodies of the rabbits. The sustained-release ligustrazine implants significantly reduced the development of PVR in the animal model.
  
  
  CONCLUSIONS
  Ligustrazine implants can be used to treat posterior ocular disease in rabbit animal models, and it provides more choices for medical research on posterior ocular disease.
authors.affiliation: School of Pharmacy, Yantai University, Yantai, Shandong, China; State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Junhua
authors.initials: J
authors.lastname: Wei
authors.forename: Pengkai
authors.initials: P
authors.lastname: Ma
authors.forename: Hongjie
authors.initials: H
authors.lastname: Mu
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.forename: Leiming
authors.initials: L
authors.lastname: Zhang
authors.forename: Zimei
authors.initials: Z
authors.lastname: Wu
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
mesh_terms: D020341:Absorbable Implants / Q000592:standards; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011719:Pyrazines / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D012160:Retina / Q000473:pathology; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy*; D014822:Vitreous Body / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D011719:Pyrazines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C017953:tetramethylpyrazine
keywords: in-vitro/in-vivo correlation; pharmacodynamics; pharmacokinetics; poly(DL-lactide-co-glycolide); posterior ocular disease