title: Pharmacokinetics and distributions of bevacizumab by intravitreal injection of bevacizumab-PLGA microspheres in rabbits.
abstract: OBJECTIVE
  To investigate the pharmacokinetics and distributions of bevacizumab by intravitreal injection of prepared bevacizumab-poly (L-lactic-co-glycolic acid) (PLGA) microspheres in rabbits, to provide evidence for clinical application of this kind of bevacizumab sustained release dosage form.
  
  
  METHODS
  Bevacizumab was encapsulated into PLGA microsphere via the solid-in-oil-in-hydrophilic oil (S/O/hO) method. Fifteen healthy New Zealand albino-rabbits were used in experiments. The eyes of each rabbit received an intravitreal injection. The left eyes were injected with prepared bevacizumab-PLGA microspheres and the right eyes were injected with bevacizumab solution. After intravitreal injection, rabbits were randomly selected at days 3, 7, 14, 28 and 42 respectively, three animals each day. Then we used immunofluorescence staining to observe the distribution and duration of bevacizumab in rabbit eye tissues, and used the sandwich ELISA to quantify the concentration of free bevacizumab from the rabbit aqueous humor and vitreous after intravitreal injection.
  
  
  RESULTS
  The results show that the concentration of bevacizumab in vitreous and aqueous humor after administration of PLGA formulation was higher than that of bevacizumab solution. The T1/2 of intravitreal injection of bevacizumab-PLGA microspheres is 9.6d in vitreous and 10.2d in aqueous humor, and the T1/2 of intravitreal injection of soluble bevacizumab is 3.91d in vitreous and 4.1d in aqueous humor. There were statistical significant difference for comparison the results of the bevacizumab in vitreous and aqueous humor between the left and right eyes (P<0.05). The AUC0-t of the sustained release dosage form was 1-fold higher than that of the soluble form. The relative bioavailability was raised significantly. The immunofluorescence staining of PLGA-encapsulated bevacizumab (b-PLGA) in rabbit eye tissues was still observed up to 42d. It was longer than that of the soluble form.
  
  
  CONCLUSIONS
  The result of this study shows the beneficial effects of PLGA in prolonging the residency of bevacizumab in the vitreous. And the drug delivery system may have potential as a treatment modality for related disease.
authors: Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China ; The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.
authors: Zhuo
authors: Z
authors: Ye
authors: Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China ; Department of Ophthalmology, the Second People's Hospital of Zhengzhou, Zhengzhou 450006, Henan Province, China.
authors: Yan-Li
authors: YL
authors: Ji
authors: Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors: Xiang
authors: X
authors: Ma
authors: The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.
authors: Jian-Guo
authors: JG
authors: Wen
authors: Department of Ophthalmology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
authors: Wei
authors: W
authors: Wei
authors: The Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.
authors: Shu-Man
authors: SM
authors: Huang
keywords: bevacizumab-PLGA microspheres; immunohistochemistry; intravitreal injection; pharmacokinetic; sustained release